Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  928 HFQLRHGNDLLAMDAIQGCDVNLKEQGQLVRQDEFTVRAGRHKACRRVFLFEELLLFSKPRRGPAGVDIFTYKRSFKMAD 1007
Cdd:cd13242      1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1402371426 1008 LGLTECCGESQLRFEIWFRRRKARDLFVLQASDVATKQAWTADISRLLWRQAVHNK 1063
Cdd:cd13242     81 IGLTENVGDSGLKFEIWFRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  446 RSAVDKADALYGQVDEL--LHQLALKSNQRIRALELLQA-----------LEAQEGVLRQIEVWLQEVGWpGVEEPGEPS 512
Cdd:COG4913    221 PDTFEAADALVEHFDDLerAHEALEDAREQIELLEPIRElaeryaaarerLAELEYLRAALRLWFAQRRL-ELLEAELEE 299

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  513 LDTLLQAQGpfQELDLVAQEQVTQGEKLLQplvgLEAAELGSPGKRFLALRSQLTEFSRALAQRRQRLADAEKLFQFFKQ 592
Cdd:COG4913    300 LRAELARLE--AELERLEARLDALREELDE----LEAQIRGNGGDRLEQLEREIERLERELEERERRRARLEALLAALGL 373

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1402371426  593 ASTWTEEG--------RRLLTELEQERPEVVLQR 618
Cdd:COG4913    374 PLPASAEEfaalraeaAALLEALEEELEALEEAL 407

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  928 HFQLRHGNDLLAMDAIQGCDVNLKEQGQLVRQDEFTVRAGRHKACRRVFLFEELLLFSKPRRGPAGVDIFTYKRSFKMAD 1007
Cdd:cd13242      1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1402371426 1008 LGLTECCGESQLRFEIWFRRRKARDLFVLQASDVATKQAWTADISRLLWRQAVHNK 1063
Cdd:cd13242     81 IGLTENVGDSGLKFEIWFRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  765 VLAEMVATEREYVRALDYTIQNYFPELDRPDvpQGLRGQRAHLFGNLEKLRDFHYNFFLRELEACTRHPPRVAHAFLRHR 844
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPL--SESEEEIKTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  845 VQFGMYALYSKNKPRSDALMTNYG------HTFFKEKQQALGDH-LDLASYLLKPIQHMSKYALLLQELARACGGPAQEL 917
Cdd:pfam00621   79 PGFKVYSTYCSNYPKALKLLKKLLkknpkfRAFLEELEANPECRgLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDY 158

                          170
                   ....*....|
gi 1402371426  918 GALQAAQSLV 927
Cdd:pfam00621  159 EDLKKALEAI 168

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426   953 QGQLVRQDEfTVRAGRHKacRRVFLFEELLLFSKPRRGpagVDIFTYKRSFKMADLGLTEC----CGESQLRFEIWFRRR 1028
Cdd:smart00233    4 EGWLYKKSG-GGKKSWKK--RYFVLFNSTLLYYKSKKD---KKSYKPKGSIDLSGCTVREApdpdSSKKPHCFEIKTSDR 77

                            90       100
                    ....*....|....*....|....*..
gi 1402371426  1029 KardLFVLQASDVATKQAWTADISRLL 1055
Cdd:smart00233   78 K---TLLLQAESEEEREKWVEALRKAI 101

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  953 QGQLVRQDEFtVRAGRHKacRRVFLFEELLLFSKPRRGPAGvdiFTYKRSFKMADLGLTECCGESQ----LRFEIWFRRR 1028
Cdd:pfam00169    4 EGWLLKKGGG-KKKSWKK--RYFVLFDGSLLYYKDDKSGKS---KEPKGSISLSGCEVVEVVASDSpkrkFCFELRTGER 77

                           90       100
                   ....*....|....*....|....*..
gi 1402371426 1029 KARDLFVLQASDVATKQAWTADISRLL 1055
Cdd:pfam00169   78 TGKRTYLLQAESEEERKDWIKAIQSAI 104

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426   230 DVEGRAVLLLCAHSpawLHPKS-NSHELLSLLFYL----RGIPRPEVQALGLTVLVDARvCSPSSSLTWGLSR-----LQ 299
Cdd:smart00516   16 DKDGRPVLIERAGR---FDLKSvTLEELLRYLVYVlekiLQEEKKTGGIEGFTVIFDLK-GLSMSNPDLSVLRkilkiLQ 91

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1402371426   300 EASPGSVQQVLLIgkmpeDVPVGLQ--WKQLR-----------------SHQSLLTHIPNVELPTSLGGSL 351
Cdd:smart00516   92 DHYPERLGKVYII-----NPPWFFRvlWKIIKpfldektrekirfvgndSKEELLEYIDKEQLPEELGGTL 157

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  928 HFQLRHGNDLLAMDAIQGCDVNLKEQGQLVRQDEFTVRAGRHKACRRVFLFEELLLFSKPRRGPAGVDIFTYKRSFKMAD 1007
Cdd:cd13242      1 RFQLRHGNDLLAMDSIRGCDVNLKEQGQLLRQDEFLVWQGRKKCLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1402371426 1008 LGLTECCGESQLRFEIWFRRRKARDLFVLQASDVATKQAWTADISRLLWRQAVHNK 1063
Cdd:cd13242     81 IGLTENVGDSGLKFEIWFRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQAIRNR 136

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  765 VLAEMVATEREYVRALDYTIQNYFPELDRPDvpQGLRGQRAHLFGNLEKLRDFHYNFFLRELEACTRHPPRVAHAFLRHR 844
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPL--SESEEEIKTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  845 VQFGMYALYSKNKPRSDALMTNYG------HTFFKEKQQALGDH-LDLASYLLKPIQHMSKYALLLQELARACGGPAQEL 917
Cdd:pfam00621   79 PGFKVYSTYCSNYPKALKLLKKLLkknpkfRAFLEELEANPECRgLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHPDY 158

                          170
                   ....*....|
gi 1402371426  918 GALQAAQSLV 927
Cdd:pfam00621  159 EDLKKALEAI 168

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  943 IQGCDVNLKEQGQLVRQDEFTV------RAGRHKAcRRVFLFEELLLFSKP--RRGPAGVDIFTYKRSFKMADLGLTECC 1014
Cdd:cd13241      4 LQGFDGKITAQGKLLLQGTLLVsepsagLLQKGKE-RRVFLFEQIIIFSEIlgKKTQFSNPGYIYKNHIKVNKMSLEENV 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1402371426 1015 GESQLRFEIWFR-RRKARDLFVLQASDVATKQAWTADISRLLWRQ 1058
Cdd:cd13241     83 DGDPLRFALKSRdPNNPSETFILQAASPEVRQEWVDTINQILDTQ 127

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  942 AIQGCDVNLKEQGQLVRQDEFTV----------RAGRHKACRR-VFLFEELLLFSKPRRGPAGVDIFTYKRSFKMADLGL 1010
Cdd:cd01227      1 AITGYDGNLGDLGKLLMQGSFNVwtehkkghtkKLARFKPMQRhIFLYEKAVLFCKKRGENGEAPSYSYKNSLNTTAVGL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1402371426 1011 TECCGESQLRFEIWFRRRKarDLFVLQASDVATKQAWTADISRLLWRQ 1058
Cdd:cd01227     81 TENVKGDTKKFEIWLNGRE--EVFIIQAPTPEIKAAWVKAIRQVLLSQ 126

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  949 NLKEQGQLVRQDEFTV-------RAGRHKACRRVFLFEELLLFSKPRRgPAGVDIFTY--KRSFKMADLGLTECCGESQL 1019
Cdd:cd13239      8 PLQALGEPIRQGHFTVweeapevKTSSRGHHRHVFLFKNCVVICKPKR-DSRTDTVTYvfKNKMKLSDIDVKDTVEGDDR 86

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1402371426 1020 RFEIWFRRRKARDLFVLQASDVATKQAWTADISRLLWR 1057
Cdd:cd13239     87 SFGLWHEHRGSVRKYTLQARSAIIKSSWLKDLRDLQQR 124

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  446 RSAVDKADALYGQVDEL--LHQLALKSNQRIRALELLQA-----------LEAQEGVLRQIEVWLQEVGWpGVEEPGEPS 512
Cdd:COG4913    221 PDTFEAADALVEHFDDLerAHEALEDAREQIELLEPIRElaeryaaarerLAELEYLRAALRLWFAQRRL-ELLEAELEE 299

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  513 LDTLLQAQGpfQELDLVAQEQVTQGEKLLQplvgLEAAELGSPGKRFLALRSQLTEFSRALAQRRQRLADAEKLFQFFKQ 592
Cdd:COG4913    300 LRAELARLE--AELERLEARLDALREELDE----LEAQIRGNGGDRLEQLEREIERLERELEERERRRARLEALLAALGL 373

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1402371426  593 ASTWTEEG--------RRLLTELEQERPEVVLQR 618
Cdd:COG4913    374 PLPASAEEfaalraeaAALLEALEEELEALEEAL 407

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  953 QGQLVRQDEFTVRAGRHkacRRVFLFEELLLFSKPRRGpagvDIFTYKRSFKMAD-LGLTEC-CGESQLRFEIWFRRRKA 1030
Cdd:cd00821      2 EGYLLKRGGGGLKSWKK---RWFVLFEGVLLYYKSKKD----SSYKPKGSIPLSGiLEVEEVsPKERPHCFELVTPDGRT 74

                           90       100
                   ....*....|....*....|.
gi 1402371426 1031 rdlFVLQASDVATKQAWTADI 1051
Cdd:cd00821     75 ---YYLQADSEEERQEWLKAL 92

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  949 NLKEQGQLVRQDEFTVRAGRHKACRR-VFLFEELLLFSKPRRGPAGVDIFTYKRSFKMADLGLTECCGESQlRFEIWFRR 1027
Cdd:cd13325      2 NIHKLGRLLRHDWFTVTDGEGKAKERyLFLFKSRILITKVRRISEDRSVFILKDIIRLPEVNVKQHPDDER-TFELQPKL 80

                           90       100
                   ....*....|....*....|....*.
gi 1402371426 1028 RKARDLFV-LQASDVATKQAWTADIS 1052
Cdd:cd13325     81 PAFGILPIdFKAHKDEIKDYWLNEIE 106

Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain family. This family includes ECM25 that contains a divergent CRAL-TRIO domain identified by Gallego and colleagues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1402371426  233 GRAVLLLCAHSPAWLHPKSNSHELLslLFYLRGIPRPEVQALGLTVLVDARVCSPSSSLTWGL-----SRLQEASPGSVQ 307
Cdd:pfam13716    1 GRPVLVFISKLLPSRPASLDDLDRL--LFYLLKTLSEKLKGKPFVVVVDHTGVTSENFPSLSFlkkayDLLPRAFKKNLK 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1402371426  308 QVLL-------------IGKMpedVPVGLQWKQLR---SHQSLLTHIPNVELPTSLGGSLSYCH 355
Cdd:pfam13716   79 AVYVvhpstflrtflktLGSL---LGSKKLRKKVHyvsSLSELWEGIDREQLPTELPGVLSYDE 139