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Conserved domains on  [gi|1720354440|ref|XP_017175021|]
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dedicator of cytokinesis protein 10 isoform X16 [Mus musculus]

Protein Classification

C2_Dock-D and DHR2_DOCK10 domain-containing protein( domain architecture ID 10570949)

protein containing domains DUF3398, PH_DOCK-D, C2_Dock-D, and DHR2_DOCK10

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
1786-2233 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


:

Pssm-ID: 212572  Cd Length: 446  Bit Score: 960.66  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1786 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTPPLLPEDTQPCDSNLLLTTPGGGSMFSM 1865
Cdd:cd11699      1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTSSMLPEDSQVYDSNLLLTTSTGGSMFSM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1866 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1945
Cdd:cd11699     81 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYYD 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1946 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 2025
Cdd:cd11699    161 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKE--YIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2026 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2105
Cdd:cd11699    239 KVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVK 318
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2106 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 2185
Cdd:cd11699    319 KRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 398
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*...
gi 1720354440 2186 VKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11699    399 VKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
761-950 4.13e-99

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


:

Pssm-ID: 176079  Cd Length: 185  Bit Score: 316.57  E-value: 4.13e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  761 YKNQIYVYPKHLKYDSQKCFNKARNITVCIEFKNSDDDGAKPMKCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIEL 840
Cdd:cd08697      1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  841 PTQLHGKHHLLFSFYHITCDInaKANAKKKEALETSVGYAWLPLMK-HDQIASQEYNIPIATTL---PPNYLSIQDPtsa 916
Cdd:cd08697     80 PTQLHEKHHLLFTFYHVSCDI--NKKGKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLpnyPDGYLSIQPH--- 154
                          170       180       190
                   ....*....|....*....|....*....|....
gi 1720354440  917 khgGSDIKWVDGGKPLFKVSTFVVSTVNTQDPHV 950
Cdd:cd08697    155 ---GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
272-392 2.12e-63

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270087  Cd Length: 126  Bit Score: 211.80  E-value: 2.12e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKGNFNST-VNNTVTVRSFKKRYFQLTQLPDNSYIMNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFEL 350
Cdd:cd13267      6 ITKEGYLYKGPENSSdSFISLAMKSFKRRFFHLKQLVDGSYILEFYKDEK-KKEAKGTIFLDSCTGVVQNSKRRKFCFEL 84
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1720354440  351 KMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGPLQGRKS 392
Cdd:cd13267     85 RMQDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
135-245 6.21e-44

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


:

Pssm-ID: 463380  Cd Length: 112  Bit Score: 155.51  E-value: 6.21e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  135 PRLLDPLDYETVIEELEKTYRDDPLQDLLFFPSDDFSTATVSWDIRTLYSTVPEEAEHRAESlLVKEACKFYSSQWYVVN 214
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAEKEADP-LVRECIKTYTSDWHVVN 79
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1720354440  215 YKYEQYSGDIRQLPRAE--HKPEKLPSHSFEVD 245
Cdd:pfam11878   80 YKYEDYSGDFRQLPKSKrrERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
1786-2233 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212572  Cd Length: 446  Bit Score: 960.66  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1786 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTPPLLPEDTQPCDSNLLLTTPGGGSMFSM 1865
Cdd:cd11699      1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTSSMLPEDSQVYDSNLLLTTSTGGSMFSM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1866 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1945
Cdd:cd11699     81 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYYD 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1946 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 2025
Cdd:cd11699    161 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKE--YIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2026 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2105
Cdd:cd11699    239 KVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVK 318
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2106 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 2185
Cdd:cd11699    319 KRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 398
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*...
gi 1720354440 2186 VKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11699    399 VKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
761-950 4.13e-99

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176079  Cd Length: 185  Bit Score: 316.57  E-value: 4.13e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  761 YKNQIYVYPKHLKYDSQKCFNKARNITVCIEFKNSDDDGAKPMKCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIEL 840
Cdd:cd08697      1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  841 PTQLHGKHHLLFSFYHITCDInaKANAKKKEALETSVGYAWLPLMK-HDQIASQEYNIPIATTL---PPNYLSIQDPtsa 916
Cdd:cd08697     80 PTQLHEKHHLLFTFYHVSCDI--NKKGKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLpnyPDGYLSIQPH--- 154
                          170       180       190
                   ....*....|....*....|....*....|....
gi 1720354440  917 khgGSDIKWVDGGKPLFKVSTFVVSTVNTQDPHV 950
Cdd:cd08697    155 ---GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
272-392 2.12e-63

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 211.80  E-value: 2.12e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKGNFNST-VNNTVTVRSFKKRYFQLTQLPDNSYIMNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFEL 350
Cdd:cd13267      6 ITKEGYLYKGPENSSdSFISLAMKSFKRRFFHLKQLVDGSYILEFYKDEK-KKEAKGTIFLDSCTGVVQNSKRRKFCFEL 84
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1720354440  351 KMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGPLQGRKS 392
Cdd:cd13267     85 RMQDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
761-949 2.42e-60

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 205.53  E-value: 2.42e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  761 YKNQIYVYPKHLKYDSQKcFNKARNITVCIEFKNSDddgAKPM-KCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIE 839
Cdd:pfam14429    4 YRNDLYVTPKSGNFSKQK-KSSARNIEVTVEVRDSD---GEPLpNCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKIA 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  840 LPTQLHGKHHLLFSFYHITCDinakanaKKKEALETSVGYAWLPLMKHDQ--IASQEYNIPIATT--LPPNYLSIQDPTS 915
Cdd:pfam14429   79 LPAELTPKHHLLFTFYHVSCD-------EKKDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKYdeLPPGYLSLPWSSG 151
                          170       180       190
                   ....*....|....*....|....*....|....
gi 1720354440  916 AKHGGSDIKWVDGGKPLFKVSTFVVSTVNTQDPH 949
Cdd:pfam14429  152 GEKESSALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
1773-1955 2.04e-55

DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs), that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminus and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DHR-2 is a GEF catalytic domain organized into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of alpha helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilizes DHR-2 domain.


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 190.20  E-value: 2.04e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1773 DLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKgywkmekictppllpedtqpcdsnl 1852
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK------------------------- 55
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1853 llttpgGGSMFSMGWPAFLSITPNI-KEEGAMKEDSGMQDTP-YNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVF 1930
Cdd:pfam06920   56 ------GKIPNPLGASAFEKISPNIlREESALKDDSGVCDSPhFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIY 129
                          170       180
                   ....*....|....*....|....*
gi 1720354440 1931 EKQRDFKKLSDLYYDIHRSYLKVAE 1955
Cdd:pfam06920  130 ESRRDYKKLSECHGKLAEAYEKIVE 154
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
135-245 6.21e-44

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 155.51  E-value: 6.21e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  135 PRLLDPLDYETVIEELEKTYRDDPLQDLLFFPSDDFSTATVSWDIRTLYSTVPEEAEHRAESlLVKEACKFYSSQWYVVN 214
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAEKEADP-LVRECIKTYTSDWHVVN 79
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1720354440  215 YKYEQYSGDIRQLPRAE--HKPEKLPSHSFEVD 245
Cdd:pfam11878   80 YKYEDYSGDFRQLPKSKrrERPEKLPKQVFEID 112
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
272-380 2.67e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 70.66  E-value: 2.67e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440   272 VFKSGWLYKgnfnstvNNTVTVRSFKKRYFQLTqlpdNSYIMnFYKDEK--ISKEPKGCIFLDSCT---GVVQNNRLRKY 346
Cdd:smart00233    1 VIKEGWLYK-------KSGGGKKSWKKRYFVLF----NSTLL-YYKSKKdkKSYKPKGSIDLSGCTvreAPDPDSSKKPH 68
                            90       100       110
                    ....*....|....*....|....*....|....
gi 1720354440   347 AFELKMNDLTYFVLAAETESDMDEWIHTLNRILQ 380
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
272-379 4.79e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 64.51  E-value: 4.79e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYK-GNFNSTvnntvtvrSFKKRYFQLTqlpdNSYIMnFYKDEKI--SKEPKGCIFLDSCTGV---VQNNRLRK 345
Cdd:pfam00169    1 VVKEGWLLKkGGGKKK--------SWKKRYFVLF----DGSLL-YYKDDKSgkSKEPKGSISLSGCEVVevvASDSPKRK 67
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1720354440  346 YAFELKMNDLTY---FVLAAETESDMDEWIHTLNRIL 379
Cdd:pfam00169   68 FCFELRTGERTGkrtYLLQAESEEERKDWIKAIQSAI 104
 
Name Accession Description Interval E-value
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
1786-2233 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212572  Cd Length: 446  Bit Score: 960.66  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1786 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTPPLLPEDTQPCDSNLLLTTPGGGSMFSM 1865
Cdd:cd11699      1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTSSMLPEDSQVYDSNLLLTTSTGGSMFSM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1866 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1945
Cdd:cd11699     81 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYYD 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1946 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 2025
Cdd:cd11699    161 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKE--YIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2026 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2105
Cdd:cd11699    239 KVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVK 318
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2106 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 2185
Cdd:cd11699    319 KRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 398
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*...
gi 1720354440 2186 VKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11699    399 VKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
1787-2233 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class D, also called the Zizimin subfamily, includes Dock9, 10 and 11. Class D Docks are specific GEFs for Cdc42. Dock9 plays important roles in spine formation and dendritic growth. Dock10 and Dock11 are preferentially expressed in lymphocytes. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class D DOCKs, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212567  Cd Length: 376  Bit Score: 675.21  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1787 ELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKgywkmekictppllpedtqpcdsnlllttpgggsmfsmg 1866
Cdd:cd11694      1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKRK--------------------------------------- 41
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1867 wpaflsitpnikeegamkedsgmqdtpyneNILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYDI 1946
Cdd:cd11694     42 ------------------------------DLLLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTL 91
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1947 HRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNK 2026
Cdd:cd11694     92 HRAYEKVVEVMESGKRLLGTYYRVAFYGQAFFEEEDGKE--YIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGK 169
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2027 VNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVKK 2106
Cdd:cd11694    170 VNPKDLDPKYAYIQVTHVTPYFDEKELEDRKTEFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKK 249
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2107 RIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQV 2186
Cdd:cd11694    250 RIPVVQREIIELSPIEVAIDEMQSKVKELEELISTEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTVKNYPDDQV 329
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*..
gi 1720354440 2187 KLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11694    330 EDLKDVFRDFIKACGQALELNERLIKEDQREYHEVLKENYRKMVKEL 376
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
1787-2236 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also called Zizimin1, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. It plays important roles in spine formation and dendritic growth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock9, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212571  Cd Length: 415  Bit Score: 652.87  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1787 ELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGywkmekictppllpedtqpcdsnlllttpgggsMFSMG 1866
Cdd:cd11698      1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLTRKG---------------------------------MFRQG 47
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1867 WPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYDI 1946
Cdd:cd11698     48 CTAFRVITPNIDEEASMMEDVGMQDVHFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTL 127
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1947 HRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNK 2026
Cdd:cd11698    128 HRAYSKVTEVMHSGKRLLGTYFRVAFFGQGFFEDEDGKE--YIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGK 205
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2027 VNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVKK 2106
Cdd:cd11698    206 VNPKDLDSKYAYIQVTHVTPYFDEKELQERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKK 285
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2107 RIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQV 2186
Cdd:cd11698    286 RIPVMYQHHTDLNPIEVAIDEMSKKVAELRQLCSSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKV 365
                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2187 KLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSELSAI 2236
Cdd:cd11698    366 KLLKEVFRQFVEACGQALAVNERLIKEDQLEYQEEMKANYREMAKELSEI 415
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
1786-2233 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also called Zizimin2 or activated Cdc42-associated GEF (ACG), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock11 is predominantly expressed in lymphocytes and is found in high levels in germinal center B lymphocytes after T cell dependent antigen immunization. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock11, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212573  Cd Length: 413  Bit Score: 627.02  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1786 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKgywkmekictppllpedtqpcdsnlllttpgggSMFSM 1865
Cdd:cd11700      1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFLHRK---------------------------------KLFPS 47
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1866 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1945
Cdd:cd11700     48 GCAAFKKITPNIDEEGAMKEDIGMMDVHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRT 127
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1946 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 2025
Cdd:cd11700    128 LHGAYAKILEVMHTGKRLLGTFFRVAFYGQGFFEEEDGKE--YIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSN 205
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2026 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2105
Cdd:cd11700    206 KVNQKDLDPKYAHIQVTYVKPYFDDKEMAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVK 285
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2106 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 2185
Cdd:cd11700    286 KRIPVNGEKQTNLKPIDVATDEIKDKTAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKK 365
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*...
gi 1720354440 2186 VKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11700    366 VKELKEMFRKFIQACSIALELNERLIKEDQVEYHEGLKSNFRDMVKEL 413
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
1786-2233 1.21e-115

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class C, also called the Zizimin-related (Zir) subfamily, includes Dock6, 7 and 8. Class C DOCKs have been shown to have GEF activity for both Rac and Cdc42. Dock6 regulates neurite outgrowth. Dock7 plays a critical roles in the early stages of axon formation, neuronal polarity, and myelination. Dock8 regulates T and B cell numbers and functions, and plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Class C Docks, which contains the catalytic GEF activity for Rac and Cdc42.


Pssm-ID: 212568  Cd Length: 368  Bit Score: 372.02  E-value: 1.21e-115
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1786 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALiaeylkrkgywkmekictppllpedtqpcdsnlllttpgggsmfsm 1865
Cdd:cd11695      2 PDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL---------------------------------------------- 35
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1866 GWPAflsitpnikeegamkedsgmqdtpyneniLVEQlymCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1945
Cdd:cd11695     36 GLVG-----------------------------LLEQ---AAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGK 83
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1946 IHRSYLKVAEVVNsEKRLFGRYYRVAFYGqavGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 2025
Cdd:cd11695     84 LQDAFTKIEKQQG-GKRMFGTYFRVGFYG---SKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSN 159
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2026 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2105
Cdd:cd11695    160 PVDTSKLDPDKAYIQITYVEPYFDEYELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVK 239
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2106 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEE-TNAKKYPDN 2184
Cdd:cd11695    240 TRLQVVNREEIVLTPIEVAIEDVQKKTRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDiPLDPKELDR 319
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*....
gi 1720354440 2185 QVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11695    320 HQNKLRLCFKEFSKKCYDALEKNKELIGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
1784-2233 3.11e-105

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also called Zizimin-related 3 (Zir3), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. Dock8 is highly expressed in the immune system and it regulates T and B cell numbers and functions. It plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. Dock8 deficiency is a primary immune deficiency that results in extreme susceptibility to cutaneous viral infections, elevated IgE levels, and eosinophilia. It was originally described as an autosomal recessive form of hyper IgE syndrome (AR-HIES). DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock8, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212574  Cd Length: 422  Bit Score: 344.33  E-value: 3.11e-105
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1784 STPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKrkgywkmekictpplLPEDTqpcdsnlllttpgggSMF 1863
Cdd:cd11701      1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLS---------------MLEDH---------------SYL 50
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1864 SMGWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDF 1936
Cdd:cd11701     51 PVGSVSFQNISSNVLEESAVSDDILSPDEDgvcsgryFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDF 130
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1937 KKLSDLYYDIHRSYLKVAEvvNSEKRLFGRYYRVAFYGQAVGFFEEEEgkeYIYKEPKLTGLSEISQRLLKLYADKFGAD 2016
Cdd:cd11701    131 RKLASTHDKLQKAFDNIIN--KGHKRMFGTYFRVGFYGSKFGDLDEQE---FIYKEPAITKLPEISHRLEGFYGQCFGDD 205
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2017 NVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLT 2096
Cdd:cd11701    206 VVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDDYEMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILT 285
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2097 TSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEET 2176
Cdd:cd11701    286 TMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEI 365
                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1720354440 2177 NAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11701    366 PADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLITADQREYQQELKKNYNKLRENL 422
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
1787-2233 4.99e-104

Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins comprise a family of atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. They are also called the CZH (CED-5, Dock180, and MBC-zizimin homology) family, after the first family members identified. Dock180 was first isolated as a binding partner for the adaptor protein Crk. The Caenorhabditis elegans protein, Ced-5, is essential for cell migration and phagocytosis, while the Drosophila ortholog, Myoblast city (MBC), is necessary for myoblast fusion and dorsal closure. DOCKs are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1 (or Dock180), 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1, and DHR-2 (also called CZH2 or Docker). This alignment model represents the DHR-2 domain of DOCK proteins, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212566 [Multi-domain]  Cd Length: 392  Bit Score: 339.66  E-value: 4.99e-104
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1787 ELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGywkmekictPPLLPEDTQPCDSNlllttpgggsmfsmg 1866
Cdd:cd11684      1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDLKALV---------PALAESLSFPEQTS--------------- 56
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1867 wpaflsitpnikEEgamkedsgmqdtpyneniLVEQLY-MCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1945
Cdd:cd11684     57 ------------FE------------------RKEALYkKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRK 106
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1946 IHRSYLKVAEVvnseKRLFGRYYRVAFYGQAvgFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKfgadnvKIIQDSN 2025
Cdd:cd11684    107 IAKLYEKIAEK----DRLFPTYFRVGFYGKG--FPESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSE 174
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2026 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRK----TDFEMHHNINRFVFETPFTLSGKK-HGGVAEQCKRRTVLTTSHL 2100
Cdd:cd11684    175 EPDDEILDSEGQYIQITSVEPYFDDEDLVSRAapgvRQFYRNNNINTFVYERPFTKGGKKsQNEITDQWKERTILTTEES 254
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2101 FPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLC----TTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEET 2176
Cdd:cd11684    255 FPTILRRSEVVSIEEIELSPIENAIEDIEKKTEELRSLInkyrSGDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSEE 334
                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1720354440 2177 NAKKYP-DNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11684    335 YLSNYPeAEKVKKLKEAFEEFLEILKRGLALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
761-950 4.13e-99

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176079  Cd Length: 185  Bit Score: 316.57  E-value: 4.13e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  761 YKNQIYVYPKHLKYDSQKCFNKARNITVCIEFKNSDDDGAKPMKCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIEL 840
Cdd:cd08697      1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  841 PTQLHGKHHLLFSFYHITCDInaKANAKKKEALETSVGYAWLPLMK-HDQIASQEYNIPIATTL---PPNYLSIQDPtsa 916
Cdd:cd08697     80 PTQLHEKHHLLFTFYHVSCDI--NKKGKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLpnyPDGYLSIQPH--- 154
                          170       180       190
                   ....*....|....*....|....*....|....
gi 1720354440  917 khgGSDIKWVDGGKPLFKVSTFVVSTVNTQDPHV 950
Cdd:cd08697    155 ---GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
1746-2240 2.66e-98

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also called Zizimin-related 2 (Zir2), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. It plays a critical role in the initial specification of axon formation in hippocampal neurons. It affects neuronal polarity by regulating microtubule dynamics. Dock7 also plays a role in controlling myelination by Schwann cells. It may also play important roles in the function and distribution of dermal and follicular melanocytes. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock7, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212576  Cd Length: 473  Bit Score: 326.27  E-value: 2.66e-98
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1746 DLTKRIRTVLMATAQMKEHEKDPEMLVDLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLK 1825
Cdd:cd11703      1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1826 rkgywkmekictpplLPEDTQpcdsnlllttpgggsMFSMGWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENI 1898
Cdd:cd11703     81 ---------------MLEDRK---------------YLPVGCVTFQNISSNVLEESAVSDDVVSPDEEgicsgkyFTEAG 130
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1899 LVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVaeVVNSEKRLFGRYYRVAFYGQAVG 1978
Cdd:cd11703    131 LVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLATIHGKLQEAFSKI--VHQDGKRMFGTYFRVGFYGTKFG 208
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1979 FFEEEEgkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKT 2058
Cdd:cd11703    209 DLDEQE---FVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRIT 285
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2059 DFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQL 2138
Cdd:cd11703    286 YFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFA 365
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2139 CTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEY 2218
Cdd:cd11703    366 THQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEY 445
                          490       500
                   ....*....|....*....|..
gi 1720354440 2219 QEELRSHYKDMLSELSAIMNEQ 2240
Cdd:cd11703    446 QRELERNYHRLKEALQPLINRK 467
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
1785-2226 3.41e-97

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also called Zizimin-related 1 (Zir1), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. It is widely expressed and shows highest expression in the dorsal root ganglion and the brain. It regulates neurite outgrowth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock6, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212575  Cd Length: 423  Bit Score: 321.19  E-value: 3.41e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1785 TPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKrkgywkmekictpplLPEDTQpcdsnlllttpgggsMFS 1864
Cdd:cd11702      1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLS---------------MLEDCR---------------HLP 50
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1865 MGWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFK 1937
Cdd:cd11702     51 VGCVSFQNISSNVLEESAVSDDILSPDEEgicsgkyFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYK 130
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1938 KLSDLYYDIHRSYLKVAEVVNSEKRLFGRYYRVAFYGqavGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADN 2017
Cdd:cd11702    131 KLAVVHGKLQEAFNKITNQSSGWERMFGTYFRVGFYG---CKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEV 207
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2018 VKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTT 2097
Cdd:cd11702    208 VEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDTYELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTT 287
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2098 SHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETn 2177
Cdd:cd11702    288 SHAFPYIKTRINVLHREEIVLIPVEVAIEDMQKKTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEI- 366
                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1720354440 2178 akkyPDNQvKL------LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHY 2226
Cdd:cd11702    367 ----PEDP-KLfrhhnkLRLCFKDFTKRCEDALRKNKALIGPDQKEYHRELERNY 416
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
272-392 2.12e-63

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 211.80  E-value: 2.12e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKGNFNST-VNNTVTVRSFKKRYFQLTQLPDNSYIMNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFEL 350
Cdd:cd13267      6 ITKEGYLYKGPENSSdSFISLAMKSFKRRFFHLKQLVDGSYILEFYKDEK-KKEAKGTIFLDSCTGVVQNSKRRKFCFEL 84
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1720354440  351 KMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGPLQGRKS 392
Cdd:cd13267     85 RMQDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
761-949 2.42e-60

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 205.53  E-value: 2.42e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  761 YKNQIYVYPKHLKYDSQKcFNKARNITVCIEFKNSDddgAKPM-KCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIE 839
Cdd:pfam14429    4 YRNDLYVTPKSGNFSKQK-KSSARNIEVTVEVRDSD---GEPLpNCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKIA 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  840 LPTQLHGKHHLLFSFYHITCDinakanaKKKEALETSVGYAWLPLMKHDQ--IASQEYNIPIATT--LPPNYLSIQDPTS 915
Cdd:pfam14429   79 LPAELTPKHHLLFTFYHVSCD-------EKKDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKYdeLPPGYLSLPWSSG 151
                          170       180       190
                   ....*....|....*....|....*....|....
gi 1720354440  916 AKHGGSDIKWVDGGKPLFKVSTFVVSTVNTQDPH 949
Cdd:pfam14429  152 GEKESSALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
1773-1955 2.04e-55

DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs), that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminus and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DHR-2 is a GEF catalytic domain organized into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of alpha helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilizes DHR-2 domain.


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 190.20  E-value: 2.04e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1773 DLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKgywkmekictppllpedtqpcdsnl 1852
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK------------------------- 55
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1853 llttpgGGSMFSMGWPAFLSITPNI-KEEGAMKEDSGMQDTP-YNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVF 1930
Cdd:pfam06920   56 ------GKIPNPLGASAFEKISPNIlREESALKDDSGVCDSPhFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIY 129
                          170       180
                   ....*....|....*....|....*
gi 1720354440 1931 EKQRDFKKLSDLYYDIHRSYLKVAE 1955
Cdd:pfam06920  130 ESRRDYKKLSECHGKLAEAYEKIVE 154
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
761-950 9.29e-54

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 classes of Dock family proteins. The members here include: Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3. Dock-C members are GEFs for both Rac and Cdc42. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-C members contain a functionally uncharacterized domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176078  Cd Length: 179  Bit Score: 186.40  E-value: 9.29e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  761 YKNQIYVYPKHLKYDSQKcfNKARNITVCIEFKNSDDDGAKPMKCIYGKpGGPLFTSSAYTAVLHHSQNPDFSDEVKIEL 840
Cdd:cd08696      1 YRNLLYVYPQSLNFSNRL--GSARNIAVKVQLMSGEDESQALPVIFKGS-SPEEFLTEAYTAVTYHNKSPDFYDEIKIKL 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  841 PTQLHGKHHLLFSFYHITCdinakANAKKKEALETSVGYAWLPLMKHDQIASQEYNIPIATTLPPNYLSIQDPTSAKHGg 920
Cdd:cd08696     78 PADLTDNHHLLFTFYHISC-----QKKQEGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPG- 151
                          170       180       190
                   ....*....|....*....|....*....|
gi 1720354440  921 sdIKWVDGGKPLFKVSTFVVSTVNTQDPHV 950
Cdd:cd08696    152 --TKWVDNHKGVFSVSVEAVSSVHTQDSYL 179
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
135-245 6.21e-44

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 155.51  E-value: 6.21e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  135 PRLLDPLDYETVIEELEKTYRDDPLQDLLFFPSDDFSTATVSWDIRTLYSTVPEEAEHRAESlLVKEACKFYSSQWYVVN 214
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAEKEADP-LVRECIKTYTSDWHVVN 79
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1720354440  215 YKYEQYSGDIRQLPRAE--HKPEKLPSHSFEVD 245
Cdd:pfam11878   80 YKYEDYSGDFRQLPKSKrrERPEKLPKQVFEID 112
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
2134-2234 1.09e-38

DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe C which form an antiparallel four alpha-helical bundle and contains a loop known as the nucleotide sensor characterized by a conserved valine residue essential for catalytic activity.


Pssm-ID: 466570 [Multi-domain]  Cd Length: 103  Bit Score: 140.42  E-value: 1.09e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2134 ELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKE 2213
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80
                           90       100
                   ....*....|....*....|.
gi 1720354440 2214 DQLEYQEELRSHYKDMLSELS 2234
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLE 101
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
761-950 4.03e-38

C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was first identified as an 180kd proto-oncogene product c-Crk-interacting protein involved in actin cytoskeletal changes. It is now known that it has Rac-specific GEF activity, but lacks the conventional Dbl homology (DH) domain. There are 10 additional related proteins that can be divided into four classes based on sequence similarity and domain organization: Dock-A which includes Dock180/Dock1, Dock2, and Dock5; Dock-B which includes Dock3/MOCA (modifier of cell adhesion) and Dock4; Dock-C which includes Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3; and Dock-D, which includes Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Most of members of classes Dock-A and Dock-B are the GEFs specific for Rac. Those of Dock-D are Cdc42-specific GEFs while those of Dock-C are the GEFs for both. All Dock180-related proteins have two common homology domains: the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker). DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176061  Cd Length: 178  Bit Score: 141.70  E-value: 4.03e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  761 YKNQIYVYPKHLKYDSQKcfNKARNITVCIEFKNSDDDGAKPMKCIYGKpgGPlFTSSAYTAVLHHSQNPDFSDEVKIEL 840
Cdd:cd08679      1 LRNDLYVYPQSGELSKAK--SKGRNIEITVEVRDDDGDIIEPCISAPGS--GS-ELRSEYTSVVYYHKNPVFNDEIKIQL 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  841 PTQLHGKHHLLFSFYHITCDinakanAKKKEALETSVGYAWLPLMKHDQ--IASQEYNIPIAT------TLPPNYLSiqD 912
Cdd:cd08679     76 PADLTPQHHLLFTFYHVSSK------KKQGDKEETPFGYAFLPLMDKDGafIKDGDHTLPVYKydkrpdVGPSGYLS--L 147
                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1720354440  913 PTSAkhggsdiKWVDGGKPLFKVSTFVVSTVNTQDPHV 950
Cdd:cd08679    148 PSTL-------ANGKSSKDTFKIKTRLCSTILTQDKSL 178
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
2024-2099 4.03e-37

DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe B which adopts an unusual architecture of two antiparallel beta sheets disposed in a loosely packed orthogonal arrangement. This lobe changes its position relative to lobe C and the bound GTPase, which suggests that lobe B distinguishes between the switch 1 conformations of Rac1 and Cdc42.


Pssm-ID: 466571 [Multi-domain]  Cd Length: 77  Bit Score: 134.66  E-value: 4.03e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720354440 2024 SNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSH 2099
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEH 76
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
1899-2229 7.47e-17

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. Class A DOCKs are specific GEFs for Rac. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock2 plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class A DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212570  Cd Length: 400  Bit Score: 85.46  E-value: 7.47e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1899 LVEQLYM-CVEFLWKSERYELIADVNKPIIAVFEKQR-DFKKLSDLYYDIHRSYLKVAEVVNSEKRlfgrYYRVAFYGQA 1976
Cdd:cd11697     59 LKEALYYdIIDYFDKGKMWECAISLCKELAEQYENETfDYLQLSELLKRMATFYDNIMKTLRPEPE----YFRVGYYGQG 134
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1977 vgFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKfgadnvkiiQDSNKVNPKDLDPKYA---YIQVTYVTPFFEE--- 2050
Cdd:cd11697    135 --FPSFLRNKVFIYRGKEYERLSDFSARLLNQFPNA---------ELMNTLTPPGDEIKESpgqYLQINKVDPVMDErpr 203
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2051 ---KEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGG-VAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAID 2126
Cdd:cd11697    204 fkgKPVSDQILNYYKVNEVQRFTFSRPFRRGTKDPDNeFANMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIE 283
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2127 EMSRKVSELNQLCTTEEVD----MIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKL--LKEIFRQFADAC 2200
Cdd:cd11697    284 TMEDTNKKIRDLILQHQSDptlpINPLSMLLNGIVDAAVMGGIANYEKAFFTEEYLDEHPEDQELIerLKDLIAEQIPLL 363
                          330       340
                   ....*....|....*....|....*....
gi 1720354440 2201 GQALDVNERLIKEDQLEYQEELRSHYKDM 2229
Cdd:cd11697    364 EAGLKIHKQKAPESLRPLHERMEECFAKM 392
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
272-380 2.67e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 70.66  E-value: 2.67e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440   272 VFKSGWLYKgnfnstvNNTVTVRSFKKRYFQLTqlpdNSYIMnFYKDEK--ISKEPKGCIFLDSCT---GVVQNNRLRKY 346
Cdd:smart00233    1 VIKEGWLYK-------KSGGGKKSWKKRYFVLF----NSTLL-YYKSKKdkKSYKPKGSIDLSGCTvreAPDPDSSKKPH 68
                            90       100       110
                    ....*....|....*....|....*....|....
gi 1720354440   347 AFELKMNDLTYFVLAAETESDMDEWIHTLNRILQ 380
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
1924-2233 3.88e-13

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. Dock3 is a specific GEF for Rac and it regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class B DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212569  Cd Length: 391  Bit Score: 73.63  E-value: 3.88e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1924 KPIIAVFEKQRDFKKLSDlyydIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQ 2003
Cdd:cd11696     81 RELAELYESLYDYAKLSH----ILRMEASFYDNILTQLRPEPEYFRVGFYGKGFPLFLRNKQ--FVYRGLDYERIGAFTQ 154
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2004 RLLKLYAdkfgadNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKE------IEDRKTDFEMHHNINRFVFETPFtl 2077
Cdd:cd11696    155 RLQSEFP------QAHILTKNTPPDDAILQADGQYIQICNVKPVPERRPvlqmvgVPDKVRSFYRVNDVRKFQYDRPI-- 226
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2078 sgkkHGGVAEQCKR-------RTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIR-- 2148
Cdd:cd11696    227 ----HKGPIDKDNEfkslwieRTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQADPTRni 302
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2149 --LQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDN--QVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRS 2224
Cdd:cd11696    303 npFSMRLQGVIDAAVNGGIAKYQEAFFTPEFILSHPEDaeHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRLVE 382

                   ....*....
gi 1720354440 2225 HYKDMLSEL 2233
Cdd:cd11696    383 RFTQMKQSL 391
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
272-378 1.73e-12

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 65.90  E-value: 1.73e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKgnfnSTVNNTVTVRSFKKRYFQL--TQLPDNSYIMNFYKDEKiSKEPKGCIFLDSC----TGVVQNNRLRK 345
Cdd:cd13324      1 VVYEGWLTK----SPPEKKIWRAAWRRRWFVLrsGRLSGGQDVLEYYTDDH-CKKLKGIIDLDQCeqvdAGLTFEKKKFK 75
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1720354440  346 YA--FELKMNDLTYFvLAAETESDMDEWIHTLNRI 378
Cdd:cd13324     76 NQfiFDIRTPKRTYY-LVAETEEEMNKWVRCICQV 109
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
1894-2192 2.25e-12

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It functions upstream of Rac1 to regulate osteoclast function. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock5, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock5, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212581  Cd Length: 400  Bit Score: 71.51  E-value: 2.25e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1894 YNENILVEQLYM-CVEFLWKSERYELIADVNKPIIAVFEKQR-DFKKLSDLYYDIHRSYlkvaEVVNSEKRLFGRYYRVA 1971
Cdd:cd11708     54 YTQQELKERLYQeIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFY----ENIMKAMRPQPEYFAVG 129
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1972 FYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDldpkyaYIQVTYVTPF---- 2047
Cdd:cd11708    130 YYGQGFPSFLRNKI--FIYRGKEYERLEDFSLKLLTQFPNAEKMTSTSPPGDEIKSSTKQ------YVQCFTVKPVmnlp 201
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2048 --FEEKEIEDRKTDFEMHHNINRFVFETPFTlSGKK--HGGVAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEV 2123
Cdd:cd11708    202 shYKDKPVPEQILNYYRANEVQQFQYSRPFR-KGEKdpDNEFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLEN 280
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720354440 2124 AIDEM---SRKVSEL-NQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ--VKLLKEI 2192
Cdd:cd11708    281 AIETMeltNEKISNLvQQHAWDRSLPVHPLSMLLNGIVDPAVMGGFSNYEKAFFTEKYLQEHPEDQekIELLKQL 355
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
1937-2233 4.35e-12

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock3 is a specific GEF for Rac. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock3, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212577  Cd Length: 392  Bit Score: 70.42  E-value: 4.35e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1937 KKLSDLYYDihrsylkvaeVVNSEKRLFGRYYRVAFYGQAVgfFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGad 2016
Cdd:cd11704    100 RKMEAAYYD----------NIMEQQRLEPEFFRVGFYGRKF--PFFLRNKEYVCRGHDYERLEAFQQRMLSEFPQAIA-- 165
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2017 nvkiIQDSNKVNPKDLDPKYAYIQVTYVTPF------FEEKEIEDRKTDFEMHHNINRFVFETPFTLSGK-KHGGVAEQC 2089
Cdd:cd11704    166 ----MQHPNHPDDGILQCDAQYLQIYAVTPIpdnmdvLQMDRVPDRIKSFYRVNNVRKFRYDRPFHKGPKdKENEFKSLW 241
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2090 KRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIR-----LQLKLQGSVSVKVNAG 2164
Cdd:cd11704    242 IERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQYQHKQLHgninlLSMCLNGVIDAAVNGG 321
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720354440 2165 PMAYARAFLEETNAKKYPDNQVKL--LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11704    322 IARYQEAFFDKDYISKHPGDAEKItqLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
274-377 4.56e-12

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 64.95  E-value: 4.56e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYK-GNFNstvnntvtvRSFKKRYFQLTqlpDNsyiMNFYKDEKISKEPKGCIFLDSCTgVVQNNRLRKYAFELKM 352
Cdd:cd13288     10 KEGYLWKkGERN---------TSYQKRWFVLK---GN---LLFYFEKKGDREPLGVIVLEGCT-VELAEDAEPYAFAIRF 73
                           90       100
                   ....*....|....*....|....*...
gi 1720354440  353 NDL---TYfVLAAETESDMDEWIHTLNR 377
Cdd:cd13288     74 DGPgarSY-VLAAENQEDMESWMKALSR 100
PH pfam00169
PH domain; PH stands for pleckstrin homology.
272-379 4.79e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 64.51  E-value: 4.79e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYK-GNFNSTvnntvtvrSFKKRYFQLTqlpdNSYIMnFYKDEKI--SKEPKGCIFLDSCTGV---VQNNRLRK 345
Cdd:pfam00169    1 VVKEGWLLKkGGGKKK--------SWKKRYFVLF----DGSLL-YYKDDKSgkSKEPKGSISLSGCEVVevvASDSPKRK 67
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1720354440  346 YAFELKMNDLTY---FVLAAETESDMDEWIHTLNRIL 379
Cdd:pfam00169   68 FCFELRTGERTGkrtYLLQAESEEERKDWIKAIQSAI 104
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
1879-2229 9.90e-12

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock2, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock2, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212579  Cd Length: 421  Bit Score: 69.63  E-value: 9.90e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1879 EEGAMKEDSGMQDTPYNENILVEQLY-MCVEFLWKSERYELIADVNKPIIAVFEKQ-RDFKKLSDLYYDIHRSYLKVAEV 1956
Cdd:cd11706     57 EQCASQVMQTGQQHPQTQRQLKETLYeTIIGYFDKGKMWEEAISLCKELAEQYEMEiFDYELLSQNLIQQAKFYESIMKI 136
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1957 VnsekRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYAdkfgadNVKIIQDSNKVNPKDLDPKY 2036
Cdd:cd11706    137 L----RPKPDYFAVGYYGQGFPSFLRNKV--FIYRGKEYERREDFQMQLMSQFP------NAEKLNTTSAPGDDIKNSPG 204
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2037 AYIQVTYVTPFFEE------KEIEDRKTDFEMHHNINRFVFETPFtlsgkKHGGV------AEQCKRRTVLTTSHLFPYV 2104
Cdd:cd11706    205 QYIQCFTVQPVLEEhprlknKPVPDQIINFYKSNYVQRFHYSRPV-----RKGPVdpenefASMWIERTTFVTAYKLPGI 279
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2105 KKRIQVISQSSTELNPIEVAIDEMSRK----VSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKK 2180
Cdd:cd11706    280 LRWFEVTHMSQTTISPLENAIETMSTTnekiLMMINQYQSDESLPINPLSMLLNGIVDPAVMGGFAKYEKAFFTEEYVRD 359
                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1720354440 2181 YPDNQVKL--LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDM 2229
Cdd:cd11706    360 HPEDQDKLtrLKDLIAWQIPLLGAGIKIHGKRVTDDLRPFHERMEECFKQL 410
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
272-375 3.08e-11

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241535  Cd Length: 115  Bit Score: 62.46  E-value: 3.08e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKgnfnSTVNNTVTVRSFKKRYFQLTQLP-DNSYIMNFYKDEKISKEpKGCIFLDSCTGVVQ-------NNRL 343
Cdd:cd13384      3 VVYEGWLTK----SPPEKRIWRAKWRRRYFVLRQSEiPGQYFLEYYTDRTCRKL-KGSIDLDQCEQVDAgltfetkNKLK 77
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1720354440  344 RKYAFELKMNDLTYFvLAAETESDMDEWIHTL 375
Cdd:cd13384     78 DQHIFDIRTPKRTYY-LVADTEDEMNKWVNCI 108
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
1930-2233 6.47e-11

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. It may also regulate spine morphology and synapse formation. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock4, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212578  Cd Length: 391  Bit Score: 66.59  E-value: 6.47e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1930 FEKQRDFKKLSDLYYDIHRSYLKVAEvvnsEKRLFGRYYRVAFYGQAVgfFEEEEGKEYIYKEPKLTGLSEISQRLLKLY 2009
Cdd:cd11705     87 YESYYDYRNLSKMRMMEASLYDKIMD----QQRLEPEFFRVGFYGKKF--PFFLRNKEFVCRGHDYERLEAFQQRMLNEF 160
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2010 ADKFGadnvkiIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDR-------KTDFEMHHnINRFVFETPFTLSGK-K 2081
Cdd:cd11705    161 PHAIA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRdgvpdniKSFYKVNH-IWRFRYDRPFHKGTKdK 233
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2082 HGGVAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQL---CTTEEVDMIR-LQLKLQGSV 2157
Cdd:cd11705    234 ENEFKSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLisqCQTRQMQNINpLTMCLNGVI 313
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720354440 2158 SVKVNAGPMAYARAFLEETNAKKYPDNQVKL--LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2233
Cdd:cd11705    314 DAAVNGGVSRYQEAFFVKEYILNHPEDGDKItrLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
274-375 3.47e-10

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 58.71  E-value: 3.47e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYKgnfnstvNNTVTVRSFKKRYFQLtqlpDNSYIMNFYKDEKISKEPKGCIFLDSCTGVVQNNRL-RKYAFELKM 352
Cdd:cd00821      1 KEGYLLK-------RGGGGLKSWKKRWFVL----FEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPKeRPHCFELVT 69
                           90       100
                   ....*....|....*....|...
gi 1720354440  353 NDLTYFVLAAETESDMDEWIHTL 375
Cdd:cd00821     70 PDGRTYYLQADSEEERQEWLKAL 92
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
1899-2190 4.00e-10

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also called Dock180, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. In the nervous system, it mediates attractive responses to netrin-1 and thus, plays a role in axon outgrowth and pathfinding. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock1, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock1, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212580  Cd Length: 400  Bit Score: 64.29  E-value: 4.00e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1899 LVEQLYM-CVEFLWKSERYELIADVNKPIIAVFEKQR-DFKKLSDLYYDIHRSYLKVAEVVNSEKRlfgrYYRVAFYGQA 1976
Cdd:cd11707     59 LKDQLYQeIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIVKVIRPKPD----YFAVGYYGQG 134
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 1977 VGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADkfgADNVKiiqdsnKVNPKDLDPKYA---YIQVTYVTPF------ 2047
Cdd:cd11707    135 FPTFLRNKM--FIYRGKEYERREDFEARLLTQFPN---AEKMK------TTSPPGDDIKNSsgqYIQCFTVKPLlelppk 203
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440 2048 FEEKEIEDRKTDFEMHHNINRFVFETPFTlSGKKH--GGVAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAI 2125
Cdd:cd11707    204 FQNKPVSEQIVSFYRVNEVQRFQYSRPVR-KGEKDpdNEFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAI 282
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720354440 2126 DEMSRKVSELNQLCTTEEVD----MIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLK 2190
Cdd:cd11707    283 ETMQLTNEKINNMVQQHLNDpnlpINPLSMLLNGIVDPAVMGGFANYEKAFFTEKYMQEHPEDHEKIEK 351
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
272-379 5.48e-10

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 58.93  E-value: 5.48e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYK-GNFnstvnntvtVRSFKKRYFQLtqlpdNSYIMNFYKDEKISKePKGCIFLDSCT-GVVQNNRLR--KYA 347
Cdd:cd13263      3 PIKSGWLKKqGSI---------VKNWQQRWFVL-----RGDQLYYYKDEDDTK-PQGTIPLPGNKvKEVPFNPEEpgKFL 67
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1720354440  348 FEL---------KMNDLTYfVLAAETESDMDEWIHTLNRIL 379
Cdd:cd13263     68 FEIipggggdrmTSNHDSY-LLMANSQAEMEEWVKVIRRVI 107
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
272-376 6.80e-09

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 55.36  E-value: 6.80e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKgnfnstVNNTvTVRSFKKRYFQLTQlpdnsYIMNFYKDEKiSKEPKGCIFLDSCT---GVVQNNRLRKYAF 348
Cdd:cd13248      7 VVMSGWLHK------QGGS-GLKNWRKRWFVLKD-----NCLYYYKDPE-EEKALGSILLPSYTispAPPSDEISRKFAF 73
                           90       100
                   ....*....|....*....|....*...
gi 1720354440  349 ELKMNDLTYFVLAAETESDMDEWIHTLN 376
Cdd:cd13248     74 KAEHANMRTYYFAADTAEEMEQWMNAMS 101
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
274-378 2.07e-08

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 54.01  E-value: 2.07e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYKGNFNStvnNTVTVRSFKKRYFQLTqlpDNsyIMNFYKDEKISKEPKGCIFLDSCTGVVQNNrLRKYAFELKMN 353
Cdd:cd13296      1 KSGWLTKKGGGS---STLSRRNWKSRWFVLR---DT--VLKYYENDQEGEKLLGTIDIRSAKEIVDND-PKENRLSITTE 71
                           90       100
                   ....*....|....*....|....*
gi 1720354440  354 DLTYFvLAAETESDMDEWIHTLNRI 378
Cdd:cd13296     72 ERTYH-LVAESPEDASQWVNVLTRV 95
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
274-382 3.39e-08

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 53.48  E-value: 3.39e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYK-GNFnstvnntvtVRSFKKRYFQLTQlpdnSYIMNFyKDEKI--SKEPKGCIFLDSCTGV--VQNNRLRKYAF 348
Cdd:cd13276      1 KAGWLEKqGEF---------IKTWRRRWFVLKQ----GKLFWF-KEPDVtpYSKPRGVIDLSKCLTVksAEDATNKENAF 66
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1720354440  349 ELKMNDLTYFvLAAETESDMDEWIHTLNR-ILQIS 382
Cdd:cd13276     67 ELSTPEETFY-FIADNEKEKEEWIGAIGRaIVKHS 100
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
274-380 6.79e-08

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 52.59  E-value: 6.79e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYKGNFNSTvnntvtvRSFKKRYFQLtqlpDNSYIMnfYKDEKISKEPKGCIFLDSC-------TGVVQN-NRLRK 345
Cdd:cd01251      4 KEGYLEKTGPKQT-------DGFRKRWFTL----DDRRLM--YFKDPLDAFPKGEIFIGSKeegysvrEGLPPGiKGHWG 70
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1720354440  346 YAFELKMNDLTyFVLAAETESDMDEWIHTLNRILQ 380
Cdd:cd01251     71 FGFTLVTPDRT-FLLSAETEEERREWITAIQKVLE 104
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
274-380 9.55e-08

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269954  Cd Length: 119  Bit Score: 52.70  E-value: 9.55e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYK--GNfnstvnntvtVRSFKKRYFQLTqlpDNSYimnFYKDEKISKEPKGCIFLDSCTGVVQNNRLRKYAFEL- 350
Cdd:cd01252      5 REGWLLKlgGR----------VKSWKRRWFILT---DNCL---YYFEYTTDKEPRGIIPLENLSVREVEDKKKPFCFELy 68
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1720354440  351 --------------------KMNDLTYFvLAAETESDMDEWIHTLNRILQ 380
Cdd:cd01252     69 spsngqvikacktdsdgkvvEGNHTVYR-ISAASEEERDEWIKSIKASIS 117
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
274-380 1.26e-07

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 51.53  E-value: 1.26e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYK-GNfnstvnntvTVRSFKKRYFQLtqlpDNSYIMnFYKDEK-ISKEPKGCIFLDSCTGVVQNNRLRkyAFELK 351
Cdd:cd13282      1 KAGYLTKlGG---------KVKTWKRRWFVL----KNGELF-YYKSPNdVIRKPQGQIALDGSCEIARAEGAQ--TFEIV 64
                           90       100
                   ....*....|....*....|....*....
gi 1720354440  352 MNDLTYFvLAAETESDMDEWIHTLNRILQ 380
Cdd:cd13282     65 TEKRTYY-LTADSENDLDEWIRVIQNVLR 92
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
274-375 3.48e-07

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 50.08  E-value: 3.48e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYKgnfNSTVNNTvtvRSFKKRYFQLtqlpDNSYIMnFYKDEKiSKEPKGCIFLDSCTGV--VQNNRlrkyaFELK 351
Cdd:cd13253      2 KSGYLDK---QGGQGNN---KGFQKRWVVF----DGLSLR-YFDSEK-DAYSKRIIPLSAISTVraVGDNK-----FELV 64
                           90       100
                   ....*....|....*....|....
gi 1720354440  352 MNDLTyFVLAAETESDMDEWIHTL 375
Cdd:cd13253     65 TTNRT-FVFRAESDDERNLWCSTL 87
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
272-376 8.04e-07

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 49.55  E-value: 8.04e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKgnfnstvnNTVTVRSFKKRYFQL--TQLpdnSYimnfYKDEKISKePKGCIFLDSCTGV-VQNNRLRKYAF 348
Cdd:cd13298      6 VLKSGYLLK--------RSRKTKNWKKRWVVLrpCQL---SY----YKDEKEYK-LRRVINLSELLAVaPLKDKKRKNVF 69
                           90       100
                   ....*....|....*....|....*...
gi 1720354440  349 ELKMNDLTYFvLAAETESDMDEWIHTLN 376
Cdd:cd13298     70 GIYTPSKNLH-FRATSEKDANEWVEALR 96
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
274-376 2.75e-06

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 47.70  E-value: 2.75e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYKGNFnstvnntvTVRSFKKRYFQLTQlpdnsYIMNFYKDeKISKEPKGCIFLDSCTGVVQNNRLRK-YAFELKM 352
Cdd:cd10573      5 KEGYLTKLGG--------IVKNWKTRWFVLRR-----NELKYFKT-RGDTKPIRVLDLRECSSVQRDYSQGKvNCFCLVF 70
                           90       100
                   ....*....|....*....|....
gi 1720354440  353 NDLTYFvLAAETESDMDEWIHTLN 376
Cdd:cd10573     71 PERTFY-MYANTEEEADEWVKLLK 93
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
274-387 3.03e-06

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270094  Cd Length: 104  Bit Score: 47.71  E-value: 3.03e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYK-GNFNStvnntvtvrSFKKRYFQLTqlpDNSyiMNFYKDEKI--SKEPKGCIFLDSCTGVVQNNRLRKYAFEL 350
Cdd:cd13275      1 KKGWLMKqGSRQG---------EWSKHWFVLR---GAA--LKYYRDPSAeeAGELDGVIDLSSCTEVTELPVSRNYGFQV 66
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1720354440  351 KMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGPL 387
Cdd:cd13275     67 KTWDGKVYVLSAMTSGIRTNWIQALRKAAGLPSPPAL 103
PH_Gab1_Gab2 cd01266
Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily ...
272-383 3.80e-06

Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1 and Gab2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241297  Cd Length: 123  Bit Score: 48.02  E-value: 3.80e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKgnfnSTVNNTVTVRSFKKRYF-----QLTQLPDnsyIMNFYKDEKiSKEPKGCIFLDSC----TGVVQNNR 342
Cdd:cd01266      4 VVCSGWLRK----SPPEKKLRRYAWKKRWFvlrsgRLSGDPD---VLEYYKNDH-AKKPIRVIDLNLCeqvdAGLTFNKK 75
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1720354440  343 --LRKYAFELKMNDLTYFvLAAETESDMDEWIHTLNRILQISP 383
Cdd:cd01266     76 elENSYIFDIKTIDRIFY-LVAETEEDMNKWVRNICDICGFNP 117
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
272-375 3.16e-05

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 44.97  E-value: 3.16e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKgnfnstvnntvtVRSFKKRYFQL-TQLPDNSYIMNFYKDEK---ISKEPKGCIFLDSCTGVvqNNRL---R 344
Cdd:cd01257      3 VRKSGYLKK------------LKTMRKRYFVLrAESHGGPARLEYYENEKkfrRNAEPKRVIPLSSCFNI--NKRAdakH 68
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1720354440  345 KYAFELKMNDlTYFVLAAETESDMDEWIHTL 375
Cdd:cd01257     69 KHLIALYTKD-ECFGLVAESEEEQDEWYQAL 98
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
274-377 5.21e-05

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 45.30  E-value: 5.21e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYK----GNFNSTVNntvtvrsFKKRYFQLTqlpdNSYImNFYKDEKISK-EPKGCIFLDSCTGV--VQNNRL--R 344
Cdd:cd01238      1 LEGLLVKrsqgKKRFGPVN-------YKERWFVLT----KSSL-SYYEGDGEKRgKEKGSIDLSKVRCVeeVKDEAFfeR 68
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1720354440  345 KYAFELKMNDLTYFVLAAETESDmDEWIHTLNR 377
Cdd:cd01238     69 KYPFQVVYDDYTLYVFAPSEEDR-DEWIAALRK 100
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
272-377 1.27e-04

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 43.55  E-value: 1.27e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKGNFNSTvnntvTVRSFKKRYFQLTQlpdnsYIMNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFELK 351
Cdd:cd13308      9 VIHSGTLTKKGGSQK-----TLQNWQLRYVIIHQ-----GCVYYYKNDQ-SAKPKGVFSLNGYNRRAAEERTSKLKFVFK 77
                           90       100       110
                   ....*....|....*....|....*....|
gi 1720354440  352 M----NDLTYFVLAAETESDMDEWIHTLNR 377
Cdd:cd13308     78 IihlsPDHRTWYFAAKSEDEMSEWMEYIRR 107
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
272-379 2.41e-04

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241529  Cd Length: 116  Bit Score: 42.63  E-value: 2.41e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKgnfnstvnNTVTVRSFKKRYFQLTQlpDNSYimnFYKDEKISKePKGCIFLDSctgvVQNNRLR------- 344
Cdd:cd13378      3 VLKAGWLKK--------QRSIMKNWQQRWFVLRG--DQLF---YYKDEEETK-PQGCISLQG----SQVNELPpnpeepg 64
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1720354440  345 KYAFEL-----------KMNDLTyFVLAAETESDMDEWIHTLNRIL 379
Cdd:cd13378     65 KHLFEIlpggagdrekvPMNHEA-FLLMANSQSDMEDWVKAIRRVI 109
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
292-376 6.77e-04

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269975  Cd Length: 106  Bit Score: 41.06  E-value: 6.77e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  292 TVRSFKKRYFQLTQLpdnsyIMNFYKDEKISKEPKGC-----IFLDSCTG-VVQNNRLRKYAFELKMNDLTYFVLAAETE 365
Cdd:cd10571     19 SNRSWKNVYTVLRGQ-----ELSFYKDQKAAKSGITYaaeppLNLYNAVCeVASDYTKKKHVFRLKLSDGAEFLFQAKDE 93
                           90
                   ....*....|.
gi 1720354440  366 SDMDEWIHTLN 376
Cdd:cd10571     94 EEMNQWVKKIS 104
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
272-397 1.37e-03

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270099  Cd Length: 139  Bit Score: 41.15  E-value: 1.37e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKGNFNSTVNNtvtvrsFKKRYFQLTQ-----LPDnSYIMNFYKDEKISKEPKGCIFLDSCTGVVQNNRLRKY 346
Cdd:cd13281     12 VQLHGILWKKPFGHQSAK------WSKRFFIIKEgfllyYSE-SEKKDFEKTRHFNIHPKGVIPLGGCSIEAVEDPGKPY 84
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1720354440  347 AFELKMNDLT-YFVLAAETESDMDEWIHTLNRILQISpegplqgRKSAELAE 397
Cdd:cd13281     85 AISISHSDFKgNIILAADSEFEQEKWLDMLRESGKIT-------WKNAQLGE 129
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
272-379 1.56e-03

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) like other RhoGAPs are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241530  Cd Length: 114  Bit Score: 40.34  E-value: 1.56e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYK-GNFnstvnntvtVRSFKKRYFQLTQlpDNSYimnFYKDEKISKePKGCIFLdsctgvvQNNRLR------ 344
Cdd:cd13379      3 VIKCGWLRKqGGF---------VKTWHTRWFVLKG--DQLY---YFKDEDETK-PLGTIFL-------PGNRVTehpcne 60
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1720354440  345 ----KYAFE---------LKMNDLTYFVLAAeTESDMDEWIHTLNRIL 379
Cdd:cd13379     61 eepgKFLFEvvpggdrerMTANHETYLLMAS-TQNDMEDWVKSIRRVI 107
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
274-377 2.49e-03

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 39.12  E-value: 2.49e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  274 KSGWLYKGNFNStvnntvtVRSFKKRYFQLtqlpDNSyiMNFYKdeKISKEpkgciflDSCTGVVQNNRL---------- 343
Cdd:cd13250      1 KEGYLFKRSSNA-------FKTWKRRWFSL----QNG--QLYYQ--KRDKK-------DEPTVMVEDLRLctvkptedsd 58
                           90       100       110
                   ....*....|....*....|....*....|....
gi 1720354440  344 RKYAFELKMNDLTYfVLAAETESDMDEWIHTLNR 377
Cdd:cd13250     59 RRFCFEVISPTKSY-MLQAESEEDRQAWIQAIQS 91
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
272-376 2.79e-03

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 39.65  E-value: 2.79e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYK-GNfnstvnntvTVRSFKKRYFQLTqlpDNSyiMNFYKDEKiSKEPKGCIFLDSCTGV----VQNNRLRKY 346
Cdd:cd13271      8 VIKSGYCVKqGA---------VRKNWKRRFFILD---DNT--ISYYKSET-DKEPLRTIPLREVLKVheclVKSLLMRDN 72
                           90       100       110
                   ....*....|....*....|....*....|
gi 1720354440  347 AFELKMNDLTYFVlAAETESDMDEWIHTLN 376
Cdd:cd13271     73 LFEIITTSRTFYI-QADSPEEMHSWIKAIS 101
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
783-947 3.02e-03

C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 classes of Dock family proteins. The members here include: Dock3/MOCA (modifier of cell adhesion) and Dock4. Most of these members have been shown to be GEFs specific for Rac, although Dock4 has also been shown to interact indirectly with the Ras family GTPase Rap1, probably through Rap regulatory proteins. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-B members contain a SH3 domain upstream of the C2 domain and a proline-rich region downstream. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176077  Cd Length: 189  Bit Score: 41.21  E-value: 3.02e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  783 ARNITVCIEFknSDDDGAKPMKCIYGKPGGPLftSSAY-TAVLHHSQNPDFSDEVKIELPTQLHGKHHLLFSFYHitCDI 861
Cdd:cd08695     22 AKNIEVTMVV--LDADGQVLKDCISLGSGEPP--CSEYrSFVLYHNNSPRWNETIKLPIPIDKFRGSHLRFEFRH--CST 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  862 NAKANAKKkealetsVGYAWLPLMKHD----QIASQE---YNIPIATTL--PPNYLSIqdPTSAKHGGSdikWVDGGKPL 932
Cdd:cd08695     96 KDKGEKKL-------FGFSFVPLMREDgttlPDGSHElyvYKCDENATFldPALYLGL--PCSKEDFQG---CPNSPSPL 163
                          170       180
                   ....*....|....*....|...
gi 1720354440  933 FK--------VSTFVVSTVNTQD 947
Cdd:cd08695    164 FSrsskesfwIRTLLCSTKLTQN 186
PH1_TAPP1_2 cd13270
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, N-terminal ...
294-383 4.20e-03

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, N-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain binds PtdIns(3,4)P2. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270089  Cd Length: 118  Bit Score: 39.41  E-value: 4.20e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  294 RSFKKRYFQLTQlpdNSYIMNFYKDEK----ISKEPKGCIFLDSCTGVVQNNRLR---KYAFELKMNDLTYFvLAAETES 366
Cdd:cd13270     23 GKFLRRYFILDT---AANLLLYYMDNPqnlpVGAAPVGSLNLTYISKVSDATKQRpkaEFCFVINALSRRYF-LQANDQQ 98
                           90
                   ....*....|....*..
gi 1720354440  367 DMDEWIHTLNRILQISP 383
Cdd:cd13270     99 DLVEWVEALNNASKITV 115
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
272-385 6.14e-03

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 38.43  E-value: 6.14e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720354440  272 VFKSGWLYKGNFnstvnntvTVRSFKKRYFQLtqlpdNSYIMNFYKDEKIsKEPKGCIFLDSCTGV--VQNNRLRKYAFE 349
Cdd:cd13273      8 VIKKGYLWKKGH--------LLPTWTERWFVL-----KPNSLSYYKSEDL-KEKKGEIALDSNCCVesLPDREGKKCRFL 73
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1720354440  350 LKMNDLTYFVLAAETESDMdEWIHTLNRILQISPEG 385
Cdd:cd13273     74 VKTPDKTYELSASDHKTRQ-EWIAAIQTAIRLSQEG 108
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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