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Conserved domains on  [gi|158508506|ref|NP_035214|]
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phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma isoform 2 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
33-386 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. It's biological function remains unknown. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


:

Pssm-ID: 270721  Cd Length: 354  Bit Score: 703.57  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  33 NEELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKI 112
Cdd:cd05177    1 NKEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 113 TFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG 192
Cdd:cd05177   81 SFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 193 LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGG 272
Cdd:cd05177  161 LIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGS 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 273 IKRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQ 352
Cdd:cd05177  241 IKRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQ 320
                        330       340       350
                 ....*....|....*....|....*....|....
gi 158508506 353 DTDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 386
Cdd:cd05177  321 DTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
415-515 1.54e-64

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


:

Pssm-ID: 132806  Cd Length: 101  Bit Score: 207.84  E-value: 1.54e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 415 RVTILGFSKTHSNLYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSDHKRIRDLSHYVEQ 494
Cdd:cd06896    1 RATILGFSKKSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSDHKRVRDLNHYLEQ 80
                         90       100
                 ....*....|....*....|.
gi 158508506 495 VLRGSYEVANSDCVLSFFLSE 515
Cdd:cd06896   81 LLSGSREVANSDCVLSFFLSE 101
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
537-649 2.32e-40

C2 domain; 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.


The actual alignment was detected with superfamily member cd08381:

Pssm-ID: 417471 [Multi-domain]  Cd Length: 122  Bit Score: 143.20  E-value: 2.32e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 537 SPKVQLLMTYEDSRLTILVKHLKNIHLPDGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDE--VLGLQG 614
Cdd:cd08381    1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGlpVEDLQQ 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 158508506 615 HVLMLIVKSKTVFVgaVNIQLCSVPLN---------EEKWYPLG 649
Cdd:cd08381   81 RVLQVSVWSHDSLV--ENEFLGGVCIPlkkldlsqeTEKWYPLG 122
 
Name Accession Description Interval E-value
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
33-386 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. It's biological function remains unknown. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270721  Cd Length: 354  Bit Score: 703.57  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  33 NEELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKI 112
Cdd:cd05177    1 NKEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 113 TFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG 192
Cdd:cd05177   81 SFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 193 LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGG 272
Cdd:cd05177  161 LIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGS 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 273 IKRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQ 352
Cdd:cd05177  241 IKRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQ 320
                        330       340       350
                 ....*....|....*....|....*....|....
gi 158508506 353 DTDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 386
Cdd:cd05177  321 DTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
126-340 2.25e-73

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 236.04  E-value: 2.25e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   126 VIFKAGDDLRQDMLALQIIQVMDNAWLQE----GLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHS---------- 191
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   192 ---------------GLIGPLKENTIKKWFSQHN-HLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHM 255
Cdd:smart00146  81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFpDPSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   256 FHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEggknTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPE 335
Cdd:smart00146 161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMGD----SGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235

                   ....*
gi 158508506   336 LRGIE 340
Cdd:smart00146 236 WRSGK 240
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
415-515 1.54e-64

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132806  Cd Length: 101  Bit Score: 207.84  E-value: 1.54e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 415 RVTILGFSKTHSNLYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSDHKRIRDLSHYVEQ 494
Cdd:cd06896    1 RATILGFSKKSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSDHKRVRDLNHYLEQ 80
                         90       100
                 ....*....|....*....|.
gi 158508506 495 VLRGSYEVANSDCVLSFFLSE 515
Cdd:cd06896   81 LLSGSREVANSDCVLSFFLSE 101
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
124-337 7.00e-60

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 200.63  E-value: 7.00e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  124 ISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMI-TYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG---------- 192
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpptamv 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  193 ------------------LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIML-TKSG 253
Cdd:pfam00454  82 kilhsalnypklklefesRISLPPKVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  254 HMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEggknTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGL 333
Cdd:pfam00454 162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGP----SGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADGL 236

                  ....
gi 158508506  334 PELR 337
Cdd:pfam00454 237 PDWS 240
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
537-649 2.32e-40

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 143.20  E-value: 2.32e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 537 SPKVQLLMTYEDSRLTILVKHLKNIHLPDGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDE--VLGLQG 614
Cdd:cd08381    1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGlpVEDLQQ 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 158508506 615 HVLMLIVKSKTVFVgaVNIQLCSVPLN---------EEKWYPLG 649
Cdd:cd08381   81 RVLQVSVWSHDSLV--ENEFLGGVCIPlkkldlsqeTEKWYPLG 122
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
84-368 3.14e-40

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 158.79  E-value: 3.14e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   84 LPLNPALCIKGIDRDACSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGL----DMQ 159
Cdd:COG5032  1759 LLDKPFVLIERFEPEVSVVKSHLQRPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLW 1836
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  160 MITYGCLSTGRAQGFIEMVPDAVTLAKIHL---------------------HSGLIGPLK---------ENTIKKWFSQH 209
Cdd:COG5032  1837 IRPYKVIPLSPGSGIIEWVPNSDTLHSILReyhkrknisidqekklaarldNLKLLLKDEfftkatlksPPVLYDWFSES 1916
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  210 NHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTK-SGHMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEY 288
Cdd:COG5032  1917 FPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVE 1995
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  289 FIteGGKNTQHFqdFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQDTDLeatshFTKKIKE 368
Cdd:COG5032  1996 AM--GVSGVEGS--FRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLPCFREIQNNEIVNVLER-----FRLKLSE 2066
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
421-512 1.15e-16

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 75.84  E-value: 1.15e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   421 FSKTHSNLYLMEVTCSDN-RRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSD-----HKRIRDLSHYVEQ 494
Cdd:smart00312   7 IGDGKHYYYVIEIETKTGlEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNFseefiEKRRRGLEKYLQS 86
                           90
                   ....*....|....*...
gi 158508506   495 VLRGSYEVANSDCVLSFF 512
Cdd:smart00312  87 LLNHPELINHSEVVLEFL 104
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
433-515 9.70e-14

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 395635  Cd Length: 84  Bit Score: 66.89  E-value: 9.70e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  433 VTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHW-WHLPFTDSD-HKRIRDLSHYVEQVLRGSyEVANSDCVLS 510
Cdd:pfam00787   1 LPTFDLEEWSVRRRYSDFVELHKQLLRKFPSLIIPPLPPKvWFGRYNEEFiEKRRKGLEQYLQRLLQHP-ELRNSEVLLE 79

                  ....*
gi 158508506  511 FFLSE 515
Cdd:pfam00787  80 FLESD 84
C2 pfam00168
C2 domain;
550-648 2.60e-09

C2 domain;


Pssm-ID: 395116 [Multi-domain]  Cd Length: 104  Bit Score: 55.01  E-value: 2.60e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  550 RLTILVKHLKNIHLPDGSVPS-AHVEIYLLphpSEVRRKKTKCVPKCTDPTYNEIVVYdEVLGLQGHVLMLIVK-----S 623
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDLNGKSdPYVKVSLL---DGKQKKKTKVVKNTLNPVWNETFTF-SVPDPENQVLEIEVYdydrfG 77
                          90       100
                  ....*....|....*....|....*..
gi 158508506  624 KTVFVGAVNIQLCSVPLNE--EKWYPL 648
Cdd:pfam00168  78 RDDFLGEVRIPLSELLLGEglDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
550-645 1.68e-07

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 49.79  E-value: 1.68e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   550 RLTILVKHLKNI-HLPDGSVPSAHVEIYLLPHPSEVrrKKTKCVPKCTDPTYNEIVVYDeVLGLQGHVLMLIVKSKTV-- 626
Cdd:smart00239   1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGDPKEK--KKTKVVKNTLNPVWNETFEFE-VPPPELAELEIEVYDKDRfg 77
                           90       100
                   ....*....|....*....|..
gi 158508506   627 ---FVGAVNIQLCSVPLNEEKW 645
Cdd:smart00239  78 rddFIGQVTIPLSDLLLGGRHE 99
 
Name Accession Description Interval E-value
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
33-386 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. It's biological function remains unknown. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270721  Cd Length: 354  Bit Score: 703.57  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  33 NEELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKI 112
Cdd:cd05177    1 NKEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 113 TFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG 192
Cdd:cd05177   81 SFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 193 LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGG 272
Cdd:cd05177  161 LIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGS 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 273 IKRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQ 352
Cdd:cd05177  241 IKRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQ 320
                        330       340       350
                 ....*....|....*....|....*....|....
gi 158508506 353 DTDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 386
Cdd:cd05177  321 DTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
34-386 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. They are activated by a variety of stimuli including chemokines, cytokines, lysophosphatidic acid (LPA), insulin, and tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270710  Cd Length: 352  Bit Score: 573.08  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  34 EELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKtCHLPLNPALCIKGIDRDACSYFTSNASPLKIT 113
Cdd:cd05166    2 EEFLKQHVLVQALTSIAEKVKSAKDSARENALRRELEQLASFLLENS-FRLPLDPALEVTGVDVRSCSYFNSNALPLKLV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 114 FINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSGL 193
Cdd:cd05166   81 FRNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETLREIQTEHGL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 194 IGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 273
Cdd:cd05166  161 TGSFKDRPLADWLQKHNPSELEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFLGDAQMFGNF 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 274 KRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELrGIEDLKYVHNNLRPQD 353
Cdd:cd05166  241 KRDRVPFVLTSDMAYVINGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGV-TQDDLRYVQDALLPEL 319
                        330       340       350
                 ....*....|....*....|....*....|...
gi 158508506 354 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 386
Cdd:cd05166  320 TDAEATAHFTRMIEESLSSKFTQLNFFIHNLAQ 352
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
34-370 5.48e-160

Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class II PI3Ks comprise three catalytic isoforms that do not associate with any regulatory subunits. They selectively use PtdIns as a susbtrate to produce PtsIns(3)P. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270624  Cd Length: 334  Bit Score: 462.81  E-value: 5.48e-160
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  34 EELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFfkdiKTCHLPLNPALCIKGIDRDACSYFTSNASPLKIT 113
Cdd:cd00891    2 EELLKQVKVLDELKEIAKKIKEEPSEERKEVLEKLLQKLELP----KKFTLPLDPRMEVKGLIVEKCKVMDSKKLPLWLV 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 114 FINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG- 192
Cdd:cd00891   78 FKNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQKKYGg 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 193 LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGG 272
Cdd:cd00891  158 FGAAFKDTPISNWLKKHNPTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGNFKKKFG 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 273 IKRDRAPFIFTSEMEYFIteGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQ 352
Cdd:cd00891  238 IKRERAPFVFTPEMAYVM--GGEDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYLRDALQLD 315
                        330
                 ....*....|....*...
gi 158508506 353 DTDLEATSHFTKKIKESL 370
Cdd:cd00891  316 LSDEEAAEHFRKLIHESL 333
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
34-386 6.68e-160

Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270720  Cd Length: 353  Bit Score: 463.30  E-value: 6.68e-160
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  34 EELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKtCHLPLNPALCIKGIDRDACSYFTSNASPLKIT 113
Cdd:cd05176    2 EELEKQTRLVQLLGRVAEKVRQASGSARQVALQDGMERVQSFFQKNK-CRLPLSPSLVAKELNIKACSFFSSNAVPLKVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 114 FINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSGL 193
Cdd:cd05176   81 LVNADPLGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVEYGV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 194 IGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 273
Cdd:cd05176  161 TGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSF 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 274 KRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQD 353
Cdd:cd05176  241 KRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQT 320
                        330       340       350
                 ....*....|....*....|....*....|...
gi 158508506 354 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 386
Cdd:cd05176  321 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
34-386 4.72e-148

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 433.27  E-value: 4.72e-148
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  34 EELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKIT 113
Cdd:cd00895    2 EEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKLS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 114 FINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSGL 193
Cdd:cd00895   82 FQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHGV 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 194 IGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 273
Cdd:cd00895  162 TGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNI 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 274 KRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQD 353
Cdd:cd00895  242 KRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQD 321
                        330       340       350
                 ....*....|....*....|....*....|...
gi 158508506 354 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 386
Cdd:cd00895  322 TEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
34-386 1.77e-121

Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. In vitro, they can also phosphorylate the substrates PtdIns and PtdIns(4)P. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270709  Cd Length: 363  Bit Score: 365.42  E-value: 1.77e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  34 EELSKEQKLVKLLgdigeKVKSASDPQRKDVLKKEIgSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKIT 113
Cdd:cd05165    9 EALNKLKKLSDIL-----KEKKKSKEKVKKLLKECL-KQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRPLWLV 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 114 FINANPM---GKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLH 190
Cdd:cd05165   83 FENADPLalsGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIANIQKK 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 191 SGL--IGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQ 268
Cdd:cd05165  163 KGKvaTLAFNKDSLHKWLKEKNKTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHFLGNFK 242
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 269 TFGGIKRDRAPFIFTSEMEYFITEGGK--NTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVH 346
Cdd:cd05165  243 KKFGIKRERVPFVLTHDFVYVIARGQDntKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKDIEYLR 322
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|.
gi 158508506 347 NNLRPQDTDLEATSHFTKKIKESL-ECFPVKLNNLIHTLAQ 386
Cdd:cd05165  323 KTLALDKTEEEALKYFRKKFNEALkGSWTTKVNWFFHNVKH 363
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
34-386 1.28e-93

Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class III PI3Ks, also called Vps34 (vacuolar protein sorting 34), contain an N-terminal lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They phosphorylate only the substrate PtdIns. They interact with a regulatory subunit, Vps15, to form a membrane-associated complex. Class III PI3Ks are involved in protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signaling, and phagocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 292.90  E-value: 1.28e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  34 EELSKEQKLVKLLGDIGEKVKSASDPQRKDV--LKKEIGSLEEF-FKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPL 110
Cdd:cd00896    2 EALKRQQEFVDRLRSLMKEVKNEKGSRDKKIerLRELLSDSELGlLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMPL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 111 KITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIhLH 190
Cdd:cd00896   82 KLTFKTLD--GGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI-LK 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 191 sgligplKENTIKKWFSQHNHLKED----YEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGh 266
Cdd:cd00896  159 -------KYGSILNFLRKHNPDESGpygiKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILG- 230
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 267 aqtfggikRD----RAPFIFTSEMEYFIteGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIED- 341
Cdd:cd00896  231 --------RDpkpfPPPMKLCKEMVEAM--GGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEPDk 300
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*..
gi 158508506 342 -LKYVHNNLRPQDTDLEATSHFTKKIKESL-ECFPVkLNNLIHTLAQ 386
Cdd:cd00896  301 aVLKVQEKFRLDLSDEEAEQYFQNLIDESVnALFPA-VVETIHKIAQ 346
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
33-386 2.87e-89

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270718  Cd Length: 366  Bit Score: 282.32  E-value: 2.87e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  33 NEELSKEQKLVKLLGDIGEKvksASDPQRKDVLKKEIGSlEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKI 112
Cdd:cd05174   11 GEALSKMKALNDFVKVSSQK---ATKPQTKEMMHVCMKQ-ETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSKMKPLWI 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 113 TFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHL--- 189
Cdd:cd05174   87 MYSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIANIQLnks 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 190 HSGLIGPLKENTIKKWFSQHNHlKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQT 269
Cdd:cd05174  167 NMAATAAFNKDALLNWLKSKNP-GDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKT 245
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 270 FGGIKRDRAPFIFTSEMEYFITEG-GKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNN 348
Cdd:cd05174  246 KFGINRERVPFILTYDFVHVIQQGkTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQYLKDS 325
                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 158508506 349 LRPQDTDLEATSHFTKKIKESL-ECFPVKLNNLIHTLAQ 386
Cdd:cd05174  326 LALGKTEEEALKHFRVKFNEALrESWKTKVNWLAHNVSK 364
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
83-386 1.01e-86

Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kbeta can be activated by G-protein-coupled receptors. Deletion of PI3Kbeta in mice results in early lethality at around day three of development. PI3Kbeta plays an important role in regulating sustained integrin activation and stable platelet agrregation, especially under conditions of high shear stress. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270717 [Multi-domain]  Cd Length: 362  Bit Score: 275.30  E-value: 1.01e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  83 HLPLNPALCIKGIDRDACSYFTSNASPLKITFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMIT 162
Cdd:cd05173   54 QSPLNPSIILSELNVEKCKYMDSKMKPLWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVP 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 163 YGCLSTGRAQGFIEMVPDAVTLAKIHLHSGLI---GPLKENTIKKWFSQHNhLKEDYEKALRNFFYSCAGWCVVTFILGV 239
Cdd:cd05173  134 YGCLATGDRSGLIEVVSSAETIADIQLNSSNVaaaAAFNKDALLNWLKEYN-SGDDLERAIEEFTLSCAGYCVATYVLGI 212
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 240 CDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGIKRDRAPFIFTSEMEYFITEGGK-NTQHFQDFVELCCRAYNIVRKHS 318
Cdd:cd05173  213 GDRHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQYCEDAYLILRKNG 292
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 158508506 319 QLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQDTDLEATSHFTKKIKESL-ECFPVKLNNLIHTLAQ 386
Cdd:cd05173  293 NLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFRQKFDEALrESWTTKVNWMAHTVRK 361
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
34-367 7.16e-81

Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kgamma signaling controls diverse immune and vascular functions including cell recruitment, mast cell activation, platelet aggregation, and smooth muscle contractility. It associates with one of two regulatory subunits, p101 and p84, and is activated by G-protein-coupled receptors (GPCRs) by direct binding to their betagamma subunits. It contains an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270627  Cd Length: 367  Bit Score: 260.18  E-value: 7.16e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  34 EELSKEQKLVKLLGDIGEKVKSASdPQRKDVLKKEIGSLEEFFKDIKTCHLP------LNPALCIKGIDRDACSYFTSNA 107
Cdd:cd00894    2 HDFTQQVQVIEMLQKVTLDIKSLS-AEKYDVSSQVISQLKQKLENLQNSQLPesfrvpYDPGLRAGALVIEKCKVMASKK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 108 SPLKITFINANPMG---KNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTL 184
Cdd:cd00894   81 KPLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 185 AKIHLHS-GLIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKF 263
Cdd:cd00894  161 AKIQQSTvGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 264 LGHAQTFGGIKRDRAPFIFTSEMEYFI-TEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDL 342
Cdd:cd00894  241 LGNYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320
                        330       340
                 ....*....|....*....|....*
gi 158508506 343 KYVHNNLRPQDTDLEATSHFTKKIK 367
Cdd:cd00894  321 EYIRDALTVGKSEEDAKKHFLDQIE 345
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
32-386 3.55e-74

Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kalpha plays an important role in insulin signaling. It also mediates physiologic heart growth and provides protection from stress. Activating mutations of PI3Kalpha is associated with diverse forms of cancer at high frequency. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270719  Cd Length: 370  Bit Score: 243.04  E-value: 3.55e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  32 LNEELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIgSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLK 111
Cdd:cd05175    8 LSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQM-RRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLW 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 112 ITFINANPMG----KNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKI 187
Cdd:cd05175   87 LNWENPDIMSellfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQI 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 188 HLHSGLIGPLKEN--TIKKWFSQHNHlKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLG 265
Cdd:cd05175  167 QCKGGLKGALQFNshTLHQWLKDKNK-GEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLD 245
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 266 HAQTFGGIKRDRAPFIFTSEMEYFITEGGK---NTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDL 342
Cdd:cd05175  246 HKKKKFGYKRERVPFVLTQDFLIVISKGAQectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDI 325
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*
gi 158508506 343 KYVHNNLRPQDTDLEATSHFTKKIKESLE-CFPVKLNNLIHTLAQ 386
Cdd:cd05175  326 AYIRKTLALDKTEQEALEYFMKQMNDAHHgGWTTKMDWIFHTIKQ 370
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
126-340 2.25e-73

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 236.04  E-value: 2.25e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   126 VIFKAGDDLRQDMLALQIIQVMDNAWLQE----GLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHS---------- 191
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   192 ---------------GLIGPLKENTIKKWFSQHN-HLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHM 255
Cdd:smart00146  81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFpDPSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   256 FHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEggknTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPE 335
Cdd:smart00146 161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMGD----SGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235

                   ....*
gi 158508506   336 LRGIE 340
Cdd:smart00146 236 WRSGK 240
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
122-371 1.13e-65

Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIalpha is a 220 kDa protein found in the plasma membrane and the endoplasmic reticulum (ER). The role of PI4KIIIalpha in the ER remains unclear. In the plasma membrane, it provides PtdIns(4)P, which is then converted by PI5Ks to PtdIns(4,5)P2, an important signaling molecule. Vertebrate PI4KIIIalpha is also part of a signaling complex associated with P2X7 ion channels. The yeast homolog, Stt4p, is also important in regulating the conversion of phosphatidylserine to phosphatidylethanolamine at the ER and Golgi interface. Mammalian PI4KIIIalpha is highly expressed in the nervous system. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270711  Cd Length: 307  Bit Score: 218.23  E-value: 1.13e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 122 KNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKihlhsglIGPLKENT 201
Cdd:cd05167   48 VWQAAIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNSKSRDQ-------IGRETDNG 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 202 IKKWFSQH--NHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGkFLGHAQTFGGIKRDRAP 279
Cdd:cd05167  121 LYEYFLSKygDESTPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FIFEISPGGNLGFESAP 199
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 280 FIFTSEMEYFItEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRG--IEDLKyvhNNLRPQDTDLE 357
Cdd:cd05167  200 FKLTKEMVDLM-GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFRGqtIKNLR---ERFALEMSERE 275
                        250
                 ....*....|....
gi 158508506 358 ATSHFTKKIKESLE 371
Cdd:cd05167  276 AANFMIKLIADSYL 289
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
415-515 1.54e-64

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132806  Cd Length: 101  Bit Score: 207.84  E-value: 1.54e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 415 RVTILGFSKTHSNLYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSDHKRIRDLSHYVEQ 494
Cdd:cd06896    1 RATILGFSKKSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSDHKRVRDLNHYLEQ 80
                         90       100
                 ....*....|....*....|.
gi 158508506 495 VLRGSYEVANSDCVLSFFLSE 515
Cdd:cd06896   81 LLSGSREVANSDCVLSFFLSE 101
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
110-370 9.47e-63

Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. There are two types of PI4Ks, types II and III. Type II PI4Ks lack the characteristic catalytic kinase domain present in PI3Ks and type III PI4Ks, and are excluded from this family. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270626 [Multi-domain]  Cd Length: 286  Bit Score: 209.81  E-value: 9.47e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 110 LKITFINANPMG-KNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIH 188
Cdd:cd00893   13 IREKSPYGNLKGwKLVSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLK 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 189 LHSGLIGplKENTIKKWFsQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQ 268
Cdd:cd00893   93 KKLDSFN--KFVSLSDFF-DDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHP 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 269 tfGGIKRDRAPFIFTSemEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNN 348
Cdd:cd00893  170 --GFYGFEGAPFKLSS--EYIEVLGGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQR 245
                        250       260
                 ....*....|....*....|..
gi 158508506 349 LRPQDTDLEATSHFTKKIKESL 370
Cdd:cd00893  246 FNPELTEGELEVYVLSLINKSL 267
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
124-337 7.00e-60

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 200.63  E-value: 7.00e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  124 ISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMI-TYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG---------- 192
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpptamv 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  193 ------------------LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIML-TKSG 253
Cdd:pfam00454  82 kilhsalnypklklefesRISLPPKVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  254 HMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEggknTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGL 333
Cdd:pfam00454 162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGP----SGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADGL 236

                  ....
gi 158508506  334 PELR 337
Cdd:pfam00454 237 PDWS 240
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
124-370 1.03e-53

Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIbeta (also called Pik1p in yeast) is a 110 kDa protein that is localized to the Golgi and the nucleus. It is required for maintaining the structural integrity of the Golgi complex (GC), and is a key regulator of protein transport from the GC to the plasma membrane. PI4KIIIbeta also functions in the genesis, transport, and exocytosis of synaptic vesicles. The Drosophila PI4KIIIbeta is essential for cytokinesis during spermatogenesis. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270712 [Multi-domain]  Cd Length: 292  Bit Score: 185.76  E-value: 1.03e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 124 ISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSGLIGPLKENTIK 203
Cdd:cd05168   31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTSLLDYFER 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 204 KwFSQHNhlKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQtfGGIKRDRAPFIFT 283
Cdd:cd05168  111 T-FGDPN--SERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSP--GGLGFETAPFKLT 185
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 284 SEMEYFIteGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAG-LPELRG-----IEDLKyvhNNLRPQDTDLE 357
Cdd:cd05168  186 QEYVEVM--GGLESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGggeftIEQLR---ERFKLNLTEEE 260
                        250
                 ....*....|...
gi 158508506 358 ATSHFTKKIKESL 370
Cdd:cd05168  261 CAQFVDSLIDKSL 273
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
537-649 2.32e-40

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 143.20  E-value: 2.32e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 537 SPKVQLLMTYEDSRLTILVKHLKNIHLPDGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDE--VLGLQG 614
Cdd:cd08381    1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGlpVEDLQQ 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 158508506 615 HVLMLIVKSKTVFVgaVNIQLCSVPLN---------EEKWYPLG 649
Cdd:cd08381   81 RVLQVSVWSHDSLV--ENEFLGGVCIPlkkldlsqeTEKWYPLG 122
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
84-368 3.14e-40

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 158.79  E-value: 3.14e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   84 LPLNPALCIKGIDRDACSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGL----DMQ 159
Cdd:COG5032  1759 LLDKPFVLIERFEPEVSVVKSHLQRPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLW 1836
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  160 MITYGCLSTGRAQGFIEMVPDAVTLAKIHL---------------------HSGLIGPLK---------ENTIKKWFSQH 209
Cdd:COG5032  1837 IRPYKVIPLSPGSGIIEWVPNSDTLHSILReyhkrknisidqekklaarldNLKLLLKDEfftkatlksPPVLYDWFSES 1916
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  210 NHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTK-SGHMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEY 288
Cdd:COG5032  1917 FPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVE 1995
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  289 FIteGGKNTQHFqdFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQDTDLeatshFTKKIKE 368
Cdd:COG5032  1996 AM--GVSGVEGS--FRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLPCFREIQNNEIVNVLER-----FRLKLSE 2066
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
95-329 7.13e-39

Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family include PI3K, phosphoinositide 4-kinase (PI4K), PI3K-related protein kinases (PIKKs), and TRansformation/tRanscription domain-Associated Protein (TRAPP). PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives, while PI4K catalyze the phosphorylation of the 4-hydroxyl of PtdIns. PIKKs are protein kinases that catalyze the phosphorylation of serine/threonine residues, especially those that are followed by a glutamine. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI4Ks produce PtdIns(4)P, the major precursor to important signaling phosphoinositides. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PI3K-like catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270621 [Multi-domain]  Cd Length: 216  Bit Score: 142.47  E-value: 7.13e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  95 IDRDACSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGF 174
Cdd:cd00142    3 LDVGILKVIHSKQRPKKITLIGAD--GKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 175 IEMVPDAVTLAkihlhsgligplkenTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGH 254
Cdd:cd00142   81 IEIVKDAQTIE---------------DLLKSLWRKSPSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEPSGN 145
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 158508506 255 MFHIDFGKFLGHAQTFggIKRDRAPFIFTSEMEYFITEGGkntqHFQDFVELCCRAYNIVRKHSQLILSLLEMML 329
Cdd:cd00142  146 IFHIDFGFIFSGRKLA--EGVETVPFRLTPMLENAMGTAG----VNGPFQISMVKIMEILREHADLIVPILEHSL 214
PX_PI3K_C2 cd06883
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The ...
416-515 8.61e-29

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.


Pssm-ID: 132793  Cd Length: 109  Bit Score: 110.52  E-value: 8.61e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 416 VTILGFSKTHS----NLYLMEVTCSD-NRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFT---DSDHKRIRD 487
Cdd:cd06883    2 VSVFGFQKRYSpekyYIYVVKVTRENqTEPSFVFRTFEEFQELHNKLSLLFPSLKLPSFPARVVLGRShikQVAERRKIE 81
                         90       100
                 ....*....|....*....|....*...
gi 158508506 488 LSHYVEQVLRGSYEVANSDCVLSFFLSE 515
Cdd:cd06883   82 LNSYLKSLFNASPEVAESDLVYTFFHPL 109
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
92-330 2.03e-20

Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members include ATM (Ataxia telangiectasia mutated), ATR (Ataxia telangiectasia and Rad3-related), TOR (Target of rapamycin), SMG-1 (Suppressor of morphogenetic effect on genitalia-1), and DNA-PK (DNA-dependent protein kinase). PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). They show strong preference for phosphorylating serine/threonine residues followed by a glutamine and are also referred to as (S/T)-Q-directed kinases. They all contain a FATC (FRAP, ATM and TRRAP, C-terminal) domain. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PIKK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270708 [Multi-domain]  Cd Length: 222  Bit Score: 90.41  E-value: 2.03e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  92 IKGIDrDACSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMdNAWLQ-----EGLDMQMITYGCL 166
Cdd:cd05164    1 IASFD-PRVRILASLQKPKKITILGSD--GKEYPFLVKGDDDLRKDERVMQLFQLL-NTLLEkdketRKRNLTIRTYSVV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 167 STGRAQGFIEMVPDAVTLakihlhsgligplkENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDN 246
Cdd:cd05164   77 PLSSQSGLIEWVDNTTTL--------------KPVLKKWFNETFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLEN 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 247 IML-TKSGHMFHIDFGKFLGHAQTFGgiKRDRAPFIFTSEMEYFITEGGKNTQhFQDFVELCCRAYnivRKHSQLILSLL 325
Cdd:cd05164  143 ILIdTKTGEVVHIDFGMIFNKGKTLP--VPEIVPFRLTRNIINGMGPTGVEGL-FRKSCEQVLRVF---RKHKDKLITFL 216

                 ....*
gi 158508506 326 EMMLH 330
Cdd:cd05164  217 DTFLY 221
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
109-330 8.30e-18

Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA double strand breaks (DSBs) caused by radiation. It is activated at the site of a DSB and phosphorylates key substrates that trigger pathways that regulate DNA repair and cell cycle checkpoints at the G1/S, S phase, and G2/M transition. Patients with the human genetic disorder Ataxia telangiectasia (A-T), caused by truncating mutations in ATM, show genome instability, increased cancer risk, immunodeficiency, compromised mobility, and neurodegeneration. A-T displays clinical heterogeneity, which is correlated to the degree of retained ATM activity. ATM contains a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATM catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270715  Cd Length: 282  Bit Score: 84.13  E-value: 8.30e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 109 PLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMdNAWLQEGL-----DMQMITYGCLSTGRAQGFIEMVPDAVT 183
Cdd:cd05171   17 PKIITCIGSD--GKKYKQLVKGGDDLRQDAVMEQVFELV-NQLLKRDKetrkrKLRIRTYKVVPLSPRSGVLEFVENTIP 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 184 LAKI----HLHSGL-----IGPLKENTIKKWFSQHNHLKED-----YEK-------ALRNFFY----------------- 225
Cdd:cd05171   94 LGEYlvgaSSKSGAharyrPKDWTASTCRKKMREKAKASAEerlkvFDEicknfkpVFRHFFLekfpdpsdwferrlayt 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 226 -SCAGWCVVTFILGVCDRHNDNIML-TKSGHMFHIDFGkflghaQTFGGIKR----DRAPFIFTSE----MEYFITEGgk 295
Cdd:cd05171  174 rSVATSSIVGYILGLGDRHLNNILIdQKTGELVHIDLG------IAFEQGKLlpipETVPFRLTRDivdgMGITGVEG-- 245
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 158508506 296 ntqhfqDFVELCCRAYNIVRKHSQLILSLLEMMLH 330
Cdd:cd05171  246 ------VFRRCCEETLRVLRENKEALLTILEVLLY 274
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
421-512 1.15e-16

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 75.84  E-value: 1.15e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   421 FSKTHSNLYLMEVTCSDN-RRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSD-----HKRIRDLSHYVEQ 494
Cdd:smart00312   7 IGDGKHYYYVIEIETKTGlEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNFseefiEKRRRGLEKYLQS 86
                           90
                   ....*....|....*...
gi 158508506   495 VLRGSYEVANSDCVLSFF 512
Cdd:smart00312  87 LLNHPELINHSEVVLEFL 104
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
103-326 6.88e-16

Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, containing the Ku70/80 subunit, and a catalytic subunit, which contains a NUC194 domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is part of a multi-component system involved in non-homologous end joining (NHEJ), a process of repairing double strand breaks (DSBs) by joining together two free DNA ends of little homology. DNA-PK functions as a molecular sensor for DNA damage that enhances the signal via phosphorylation of downstream targets. It may also act as a protein scaffold that aids the localization of DNA repair proteins to the site of DNA damage. DNA-PK also plays a role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. DNA-PK is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The DNA-PK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 77.23  E-value: 6.88e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 103 FTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQE----GLDMQMITYGCLSTGRAQGFIEMV 178
Cdd:cd05172   11 LSSKRRPKRITIRGSD--EKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLIEWV 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 179 PDAVTLAKIhlhsgligpLKENTIKKWFSQHNHLKEDYeKALR-NFFYSCAGWCVVTFILGVCDRHNDNIML-TKSGHMF 256
Cdd:cd05172   89 DNTTPLKEI---------LENDLLRRALLSLASSPEAF-LALRsNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLI 158
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 257 HIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEGGKNTQHFQDFVeLCCRAYnivRKHSQLILSLLE 326
Cdd:cd05172  159 GIDFGHAFGSATQFLPIP-ELVPFRLTRQLLNLLQPLDARGLLRSDMV-HVLRAL---RAGRDLLLATMD 223
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
92-330 2.66e-15

Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to as Mei-41 (Drosophila), Esr1/Mec1p (Saccharomyces cerevisiae), Rad3 (Schizosaccharomyces pombe), and FRAP-related protein (human). ATR contains a UME domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. Together with its downstream effector kinase, Chk1, ATR plays a central role in regulating the replication checkpoint. ATR stabilizes replication forks by promoting the association of DNA polymerases with the fork. Preventing fork collapse is essential in preserving genomic integrity. ATR also plays a role in normal cell growth and in response to DNA damage. ATR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270625 [Multi-domain]  Cd Length: 237  Bit Score: 75.62  E-value: 2.66e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  92 IKGIDRDAcSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQ----EGLDMQMITYGCLS 167
Cdd:cd00892    1 ISGFEDEV-EIMPSLQKPKKITLVGSD--GKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpesRRRNLHIRTYAVIP 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 168 TGRAQGFIEMVPDAVTLAKIhlhsglIGPLKENTIKKWFsqHNHLKEDYE--KALRNFFYSCAGWCVVTFILGVCDRHND 245
Cdd:cd00892   78 LNEECGIIEWVPNTVTLRSI------LSTLYPPVLHEWF--LKNFPDPTAwyEARNNYTRSTAVMSMVGYILGLGDRHGE 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 246 NIML-TKSGHMFHIDFGKFLGHAQTFGgiKRDRAPFIFTSEMeyfI-------TEGGkntqhfqdFVELCCRAYNIVRKH 317
Cdd:cd00892  150 NILFdSTTGDVVHVDFDCLFDKGLTLE--VPERVPFRLTQNM---VdamgvtgVEGT--------FRRTCEVTLRVLREN 216
                        250
                 ....*....|...
gi 158508506 318 SQLILSLLEMMLH 330
Cdd:cd00892  217 RETLMSVLETFVH 229
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
433-515 9.70e-14

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 395635  Cd Length: 84  Bit Score: 66.89  E-value: 9.70e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  433 VTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHW-WHLPFTDSD-HKRIRDLSHYVEQVLRGSyEVANSDCVLS 510
Cdd:pfam00787   1 LPTFDLEEWSVRRRYSDFVELHKQLLRKFPSLIIPPLPPKvWFGRYNEEFiEKRRKGLEQYLQRLLQHP-ELRNSEVLLE 79

                  ....*
gi 158508506  511 FFLSE 515
Cdd:pfam00787  80 FLESD 84
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
539-648 1.74e-13

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). 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. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 67.27  E-value: 1.74e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 539 KVQLLMTYEDSRLTILVKHLKNIHLP---DGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDEVLG--LQ 613
Cdd:cd04031    4 RIQIQLWYDKVTSQLIVTVLQARDLPprdDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRetLK 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 158508506 614 GHVLMLIV----KSKT-VFVGAVNIQLCSVPLNEE-KWYPL 648
Cdd:cd04031   84 ERTLEVTVwdydRDGEnDFLGEVVIDLADALLDDEpHWYPL 124
PX_domain cd06093
The Phox Homology domain, a phosphoinositide binding module; The PX domain is a ...
416-512 3.08e-11

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.


Pssm-ID: 132768  Cd Length: 106  Bit Score: 60.45  E-value: 3.08e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 416 VTILGFSKTHSN-----LYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSD--HKRIRDL 488
Cdd:cd06093    2 VSIPDYEKVKDGgkkyvVYIIEVTTQGGEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEfiEERRKQL 81
                         90       100
                 ....*....|....*....|....
gi 158508506 489 SHYVEQVLRgSYEVANSDCVLSFF 512
Cdd:cd06093   82 EQYLQSLLN-HPELRNSEELKEFL 104
C2 pfam00168
C2 domain;
550-648 2.60e-09

C2 domain;


Pssm-ID: 395116 [Multi-domain]  Cd Length: 104  Bit Score: 55.01  E-value: 2.60e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506  550 RLTILVKHLKNIHLPDGSVPS-AHVEIYLLphpSEVRRKKTKCVPKCTDPTYNEIVVYdEVLGLQGHVLMLIVK-----S 623
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDLNGKSdPYVKVSLL---DGKQKKKTKVVKNTLNPVWNETFTF-SVPDPENQVLEIEVYdydrfG 77
                          90       100
                  ....*....|....*....|....*..
gi 158508506  624 KTVFVGAVNIQLCSVPLNE--EKWYPL 648
Cdd:pfam00168  78 RDDFLGEVRIPLSELLLGEglDGWYPL 104
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
103-330 2.85e-08

Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic domain, and a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. It is also called FRAP (FK506 binding protein 12-rapamycin associated protein). TOR is a central component of the eukaryotic growth regulatory network. It controls the expression of many genes transcribed by all three RNA polymerases. It associates with other proteins to form two distinct complexes, TORC1 and TORC2. TORC1 is involved in diverse growth-related functions including protein synthesis, nutrient use and transport, autophagy and stress responses. TORC2 is involved in organizing cytoskeletal structures. TOR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The TOR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270713 [Multi-domain]  Cd Length: 279  Bit Score: 55.57  E-value: 2.85e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 103 FTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQ----IIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMV 178
Cdd:cd05169   11 ITSKQRPRKLTIVGSD--GKEYKFLLKGHEDLRLDERVMQlfglVNTLLKNDSETSRRNLSIQRYSVIPLSPNSGLIGWV 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 179 PDAVTLAKI-----HLHSglIGPLKEN-TIKKWFSQHNHL-----KEDYEKALR-------------------------- 221
Cdd:cd05169   89 PGCDTLHSLirdyrEKRK--IPLNIEHrLMLQMAPDYDNLtliqkVEVFEYALEntpgddlrrvlwlkspsseawlerrt 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 222 NFFYSCAGWCVVTFILGVCDRHNDNIML-TKSGHMFHIDFG----------KFlghaqtfggikRDRAPF----IFTSEM 286
Cdd:cd05169  167 NFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamhreKF-----------PEKVPFrltrMLVNAM 235
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 158508506 287 EYFITEGgkntqhfqDFVELCCRAYNIVRKHSQLILSLLEMMLH 330
Cdd:cd05169  236 EVSGVEG--------TFRSTCEDVMRVLRENKDSLMAVLEAFVH 271
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
550-645 1.68e-07

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 49.79  E-value: 1.68e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506   550 RLTILVKHLKNI-HLPDGSVPSAHVEIYLLPHPSEVrrKKTKCVPKCTDPTYNEIVVYDeVLGLQGHVLMLIVKSKTV-- 626
Cdd:smart00239   1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGDPKEK--KKTKVVKNTLNPVWNETFEFE-VPPPELAELEIEVYDKDRfg 77
                           90       100
                   ....*....|....*....|..
gi 158508506   627 ---FVGAVNIQLCSVPLNEEKW 645
Cdd:smart00239  78 rddFIGQVTIPLSDLLLGGRHE 99
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
121-261 4.41e-07

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 49.36  E-value: 4.41e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 121 GKNISVIFKAGDDlRQDMLALQIIQVMDNawLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVtlakihlhSGliGPLKEN 200
Cdd:cd13968   16 CTTIGVAVKIGDD-VNNEEGEDLESEMDI--LRRLKGLELNIPKVLVTEDVDGPNILLMELV--------KG--GTLIAY 82
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 158508506 201 TIKKwfsqhnhlkEDYEKALRNFFYSCAGWCVVTFILGVC--DRHNDNIMLTKSGHMFHIDFG 261
Cdd:cd13968   83 TQEE---------ELDEKDVESIMYQLAECMRLLHSFHLIhrDLNNDNILLSEDGNVKLIDFG 136
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
538-641 5.79e-07

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 49.12  E-value: 5.79e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 538 PKVQLLMTY--EDSRLTILVKHLKNIHLPDGSV-PSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYD-EVLGLQ 613
Cdd:cd00276    1 GELLLSLSYlpTAERLTVVVLKARNLPPSDGKGlSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDvPAEQLE 80
                         90       100
                 ....*....|....*....|....*...
gi 158508506 614 GHVLMLIVKSKTVFVGAVNIQLCSVPLN 641
Cdd:cd00276   81 EVSLVITVVDKDSVGRNEVIGQVVLGPD 108
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
109-330 6.35e-07

Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical role in the mRNA surveillance mechanism known as non-sense mediated mRNA decay (NMD). NMD protects the cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) generated by genome mutations and by errors during transcription and splicing. SMG-1 phosphorylates Upf1, another central component of NMD, at the C-terminus upon recognition of PTCs. The phosphorylation/dephosphorylation cycle of Upf1 is essential for promoting NMD. In addition to its catalytic domain, SMG-1 contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. SMG-1 is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The SMG-1 catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270714  Cd Length: 304  Bit Score: 51.49  E-value: 6.35e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 109 PLKITFINANpmGKNISVIFKAGDDLRQD---MLALQIIQVM---DNAwlQEGLDMQMITYGCLSTGRAQGFIEMVPDAV 182
Cdd:cd05170   17 PKKLVFLGSD--GKRYPYLFKGLEDLHLDeriMQFLSIVNAMlasDNE--HRRRRYRARHYSVTPLGPRSGLIQWVDGAT 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 183 TLAKIH-------------------------------LHSGLIGPLKENTIKK--------------------------- 204
Cdd:cd05170   93 PLFSLYkrwqqrraaaqaqknqdsgstpppvprpselFYNKLKPALKAAGIRKstsrrewplevlrqvleelvaetprdl 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 205 -----WFSQHNhLKEDYEKaLRNFFYSCAGWCVVTFILGVCDRHNDNIMLT-KSGHMFHIDF------GKFLghaqtfgg 272
Cdd:cd05170  173 larelWCSSPS-SAEWWRV-TQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL-------- 242
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 158508506 273 ikR--DRAPFIFTSEMEYFI----TEGgkntqhfqDFVELCCRAYNIVRKHSQLILSLLEMMLH 330
Cdd:cd05170  243 --RvpEKVPFRLTQNIEHALgptgVEG--------TFRLSCEQVLKILRKGRETLLTLLEAFVY 296
PX_SNX27 cd06886
The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; The PX domain is a ...
440-495 7.71e-07

The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX27 contains an N-terminal PDZ domain followed by a PX domain and a Ras-Associated (RA) domain. It binds G protein-gated potassium (Kir3) channels, which play a role in neuronal excitability control, through its PDZ domain. SNX27 downregulates Kir3 channels by promoting their movement in the endosome, reducing surface expression and increasing degradation. SNX27 also associates with 5-hydroxytryptamine type 4 receptor (5-HT4R), cytohesin associated scaffolding protein (CASP), and diacylglycerol kinase zeta, and may play a role in their intracellular trafficking and endocytic recycling. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome.


Pssm-ID: 132796  Cd Length: 106  Bit Score: 47.79  E-value: 7.71e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 158508506 440 RSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWhlPFTDSDHK---RIRDLSHYVEQV 495
Cdd:cd06886   31 RQLCSRRYREFANLHQNLKKEFPDFQFPKLPGKW--PFSLSEQQldaRRRGLEQYLEKV 87
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
526-609 2.11e-06

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 48.09  E-value: 2.11e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 526 FVDPGENSLDKSPKVqllmtyEDSRLTILVKHLKNihLP----DGSVPSaHVEIYLLPHPSEVRRKKTKCVPKCTDPTYN 601
Cdd:cd04020   10 YVPPESEGALKSKKP------STGELHVWVKEAKN--LPalksGGTSDS-FVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                 ....*...
gi 158508506 602 EIVVYDEV 609
Cdd:cd04020   81 HTFVYDGV 88
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
572-648 3.90e-06

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. 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. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 46.27  E-value: 3.90e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 572 HVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYD-EVLGLQGHVLMLIV-----KSKTVFVGAVNIQLCSVPLNEEK- 644
Cdd:cd08393   40 YVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKvEREELPTRVLNLSVwhrdsLGRNSFLGEVEVDLGSWDWSNTQp 119

                 ....*
gi 158508506 645 -WYPL 648
Cdd:cd08393  120 tWYPL 124
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
539-652 5.31e-06

C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). 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. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175994 [Multi-domain]  Cd Length: 146  Bit Score: 46.61  E-value: 5.31e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 539 KVQLLMTYEDSRLTILVKHLKN-IHLPDGSVPSA-HVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDEvlGLQGHV 616
Cdd:cd04028   19 DIQLGLYDKKGQLEVEVIRARGlVQKPGSKVLPApYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDV--SPTGKT 96
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 158508506 617 LMLIV------KSKTVFVGAVNIQLCSVPLNEE--KWYPLGNSI 652
Cdd:cd04028   97 LQVIVwgdygrMDKKVFMGVAQILLDDLDLSNLviGWYKLFPTS 140
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
539-648 5.40e-06

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 46.11  E-value: 5.40e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 539 KVQLLMTY--EDSRLTILVKHLKNIHLPDGS-VPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDEVLG-LQG 614
Cdd:cd04030    4 RIQLTIRYssQRQKLIVTVHKCRNLPPCDSSdIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEeLKR 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 158508506 615 HVLMLIVKSK-------TVFVGAVNIQLCSVPLNE--EKWYPL 648
Cdd:cd04030   84 RTLDVAVKNSksflsreKKLLGQVLIDLSDLDLSKgfTQWYDL 126
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
551-648 9.72e-06

C2 domain; 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: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 44.75  E-value: 9.72e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 551 LTILVKHLKNIHLPD-GSVPSAHVEIYLLPHpsevRRKKTKCVPKCTDPTYNEIVVYdEVLGLQGHVLMLIVK-----SK 624
Cdd:cd00030    1 LRVTVIEARNLPAKDlNGKSDPYVKVSLGGK----QKFKTKVVKNTLNPVWNETFEF-PVLDPESDTLTVEVWdkdrfSK 75
                         90       100
                 ....*....|....*....|....*..
gi 158508506 625 TVFVGAVNIQLCSV---PLNEEKWYPL 648
Cdd:cd00030   76 DDFLGEVEIPLSELldsGKEGELWLPL 102
PX_NoxO1 cd06889
The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain ...
426-513 1.08e-05

The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1, a homolog of the p47phox subunit of phagocytic NADPH oxidase, is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of NoxO1 preferentially binds phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2], PI5P, and PI4P.


Pssm-ID: 132799  Cd Length: 121  Bit Score: 45.07  E-value: 1.08e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 426 SNLYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQF---------SSLALPEFPHWWHLPF----TDSDHKRIRDLSHYV 492
Cdd:cd06889   19 HKTYMFSVLWSDGSELFVYRSLEEFRKLHKQLKEKFpveagllrsSDRVLPKFKDAPSLGSlkgsTSRSLARLKLLETYC 98
                         90       100
                 ....*....|....*....|.
gi 158508506 493 EQVLRGSYEVANSDCVLSFFL 513
Cdd:cd06889   99 QELLRLDEKVSRSPEVIQFFA 119
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
444-512 2.44e-05

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132823  Cd Length: 109  Bit Score: 43.76  E-value: 2.44e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 158508506 444 KKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSD---HKRIRDLSHYVEQVLRGSYEVANSDCVLSFF 512
Cdd:cd07290   35 QRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEavaERRKEELNGYIWHLIHAPPEVAECDLVYTFF 106
PX_PI3K_C2_alpha cd07289
The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II ...
445-512 5.70e-05

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132822  Cd Length: 109  Bit Score: 42.61  E-value: 5.70e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 158508506 445 KSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFT---DSDHKRIRDLSHYVEQVLRGSYEVANSDCVLSFF 512
Cdd:cd07289   36 RTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRThikDVAAKRKVELNSYIQSLMNSSTEVAECDLVYTFF 106
PX_SNX17_31 cd06885
The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain ...
447-514 1.49e-04

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.


Pssm-ID: 132795  Cd Length: 104  Bit Score: 41.16  E-value: 1.49e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 158508506 447 FEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSDHKRIRD-LSHYVeQVLRGSYEVANSDCVLSFFLS 514
Cdd:cd06885   35 YSQLHGLNEQLKKEFGNRKLPPFPPKKLLPLTPAQLEERRLqLEKYL-QAVVQDPRIANSDIFNSFLLN 102
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
539-607 2.29e-04

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 41.48  E-value: 2.29e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 158508506 539 KVQLLMTYEDSRLTILVKHLKNihL----PDG-SVPsaHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYD 607
Cdd:cd04026    3 RIYLKISVKDNKLTVEVREAKN--LipmdPNGlSDP--YVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFD 72
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
540-648 2.49e-04

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 41.09  E-value: 2.49e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 540 VQLLMTYED--SRLTILVKHLKNIHLPDGS--VPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVY----DEvlg 611
Cdd:cd08521    3 IEFSLSYNYktGSLEVHIKECRNLAYADEKkkRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYhiskSQ--- 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 158508506 612 LQGHVLMLIV-----KSKTVFVGAVNIQLCSVPLN--EEKWYPL 648
Cdd:cd08521   80 LETRTLQLSVwhhdrFGRNTFLGEVEIPLDSWDLDsqQSEWYPL 123
C2B_Synaptotagmin-15 cd08409
C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking ...
540-602 4.78e-04

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176054  Cd Length: 137  Bit Score: 40.78  E-value: 4.78e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 158508506 540 VQLLMTYED--SRLTILVKHLKNIHLPDGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNE 602
Cdd:cd08409    4 IQISLTYNPtlNRLTVVVLRARGLRQLDHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNE 68
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
573-646 7.99e-04

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 39.57  E-value: 7.99e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 573 VEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDEVLG--LQGHVLMLIV----KSKTVFVGAVNIQLCSVPLNEEKWY 646
Cdd:cd04035   40 VKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYGITEedIQRKTLRLLVldedRFGNDFLGETRIPLKKLKPNQTKQF 119
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
550-607 1.16e-03

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 39.72  E-value: 1.16e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 158508506 550 RLTILVkhLKNIHLP--DGSVPS-AHVEIYLLPHPSEVRRKKTKcVPKCT-DPTYNEIVVYD 607
Cdd:cd08404   16 RLTVVV--LKARHLPkmDVSGLAdPYVKVNLYYGKKRISKKKTH-VKKCTlNPVFNESFVFD 74
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
537-648 1.40e-03

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 38.96  E-value: 1.40e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 537 SPKVQLLMTYEDSR--LTILVKHLKNIHLPDGS--VPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYD----- 607
Cdd:cd04029    1 SGEILFSLSYDYKTqsLNVHVKECRNLAYGDEAkkRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSishsq 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 158508506 608 -EVLGLQGHVLMLIVKSKTVFVGAVNIQLCSVPLN--EEKWYPL 648
Cdd:cd04029   81 lETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDsqHEECLPL 124
PX_Bem1p cd06890
The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a ...
429-512 2.01e-03

The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of Bem1p specifically binds phosphatidylinositol-4-phosphate (PI4P).


Pssm-ID: 132800  Cd Length: 112  Bit Score: 38.42  E-value: 2.01e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 429 YLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLA--------LPEFPhwwhLPFTDSD-----HKRIRDLSHYVEQV 495
Cdd:cd06890   17 YRVRATLSDGKTRYLCRYYQDFYKLHIALLDLFPAEAgrnsskriLPYLP----GPVTDVVndsisLKRLNDLNEYLNEL 92
                         90
                 ....*....|....*..
gi 158508506 496 LRGSYEVANSDCVLSFF 512
Cdd:cd06890   93 INLPAYIQTSEVVRDFF 109
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
546-645 3.07e-03

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 38.01  E-value: 3.07e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 546 YEDSRLTILVKHLKNIHLPDGSVPSAH----VEIYLLPhpSEVRRKKTKCVPKCTDPTYNEIVVYD-EVLGLQGHVLMLI 620
Cdd:cd08390    9 YDLEEEQLTVSLIKARNLPPRTKDVAHcdpfVKVCLLP--DERRSLQSKVKRKTQNPNFDETFVFQvSFKELQRRTLRLS 86
                         90       100       110
                 ....*....|....*....|....*....|
gi 158508506 621 V-----KSKTVFVGAVniqlcSVPLNEEKW 645
Cdd:cd08390   87 VydvdrFSRHCIIGHV-----LFPLKDLDL 111
C2_RGS-like cd08685
C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of ...
539-648 9.33e-03

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. 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: 176067 [Multi-domain]  Cd Length: 119  Bit Score: 36.66  E-value: 9.33e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158508506 539 KVQLLMTYEDSRLTILVKHLKNIHLPDGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDEVLGLQGHVLM 618
Cdd:cd08685    2 QLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRLL 81
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 158508506 619 LIVKSK------TVFVGAVNIQLCSVPLNEE--KWYPL 648
Cdd:cd08685   82 VTVWNKlsksrdSGLLGCMSFGVKSIVNQKEisGWYYL 119
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.19
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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