Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and Sec7 domain containing) is an guanine nucleotide exchange factor for ADP ribosylation factor 6 (ARF6), which is involved in membrane recycling. EFA6 has four structurally related polypeptides: EFA6A, EFA6B, EFA6C and EFA6D. It consists of a N-terminal proline rich region (PR), a SEC7 domain, a PH domain, a PR, a coiled-coil region, and a C-terminal PR. The EFA6 PH domain regulates its association with the plasma membrane. EFA6 activates Arf6 through its Sec7 catalytic domain and modulates this activity through its C-terminal domain, which rearranges the actin cytoskeleton in fibroblastic cell lines. 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 49116160  772 DPTVPTYKQGILARKMHQDADGKKTPWGKRGWKMFHTLLRGMVLYFLKqGEDHCLEGesLVGQMVDEPVGVHHSLATPAT 851
Cdd:cd13295    1 DPNAVEYKKGYLMRKCCADPDGKKTPFGKRGWKMFYATLKGLVLYLHK-DEYGCKKA--LRYESLRNAISVHHSLATKAT 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 49116160  852 HYTKKPHVFQLRTADWRLYLFQAPTAKEMSSWIARINLAAATHSAPPFP 900
Cdd:cd13295   78 DYTKKPHVFRLRTADWREYLFQASDTKEMQSWIEAINLVAAAFSAPPLP 126

Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and Sec7 domain containing) is an guanine nucleotide exchange factor for ADP ribosylation factor 6 (ARF6), which is involved in membrane recycling. EFA6 has four structurally related polypeptides: EFA6A, EFA6B, EFA6C and EFA6D. It consists of a N-terminal proline rich region (PR), a SEC7 domain, a PH domain, a PR, a coiled-coil region, and a C-terminal PR. The EFA6 PH domain regulates its association with the plasma membrane. EFA6 activates Arf6 through its Sec7 catalytic domain and modulates this activity through its C-terminal domain, which rearranges the actin cytoskeleton in fibroblastic cell lines. 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 49116160  772 DPTVPTYKQGILARKMHQDADGKKTPWGKRGWKMFHTLLRGMVLYFLKqGEDHCLEGesLVGQMVDEPVGVHHSLATPAT 851
Cdd:cd13295    1 DPNAVEYKKGYLMRKCCADPDGKKTPFGKRGWKMFYATLKGLVLYLHK-DEYGCKKA--LRYESLRNAISVHHSLATKAT 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 49116160  852 HYTKKPHVFQLRTADWRLYLFQAPTAKEMSSWIARINLAAATHSAPPFP 900
Cdd:cd13295   78 DYTKKPHVFRLRTADWREYLFQASDTKEMQSWIEAINLVAAAFSAPPLP 126

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49116160     590 NLASRLYRLEGFRKSEVAAYLQKNNDFSRAVAEEYLSFFQFGGQSLDRALRSFLQALVLSGETQERERILYQFSRRFHHC 669
Cdd:smart00222   39 DVADFLSKNEGLNKKAIGDYLGEHDEFNRLVLHAFVDLFDFSAKDLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCEC 118

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 49116160     670 NPGIF--PSVDSVHTLTCAIMLLNTDLHGQNIGKSMSCQEFITNLNGLRDGGNFPKELLKALYWSIRSEKL 738
Cdd:smart00222  119 NPGVFskANADAAYTLAYSLIMLNTDLHNPNVKKKMTLEDFIKNVRGSNDGEDLPREFLEELYDSIKNNEI 189

ARF guanine nucleotide exchange factor (ARF-GEF); Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49116160   600 GFRKSEVAAYLQKNNDFSRAVAEEYLSFFQFGGQSLDRALRSFLQALVLSGETQERERILYQFSRRFHHCNPGIFPSVDS 679
Cdd:PLN03076  660 GLNKTLIGDYLGEREDLSLKVMHAYVDSFDFQGMEFDEAIRAFLQGFRLPGEAQKIDRIMEKFAERYCKCNPKAFSSADT 739

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 49116160   680 VHTLTCAIMLLNTDLHGQNIGKSMSCQEFITNLNGLRDGGNFPKELLKALYWSIRSEKLEWavdEEDTARPEKAQPS 756
Cdd:PLN03076  740 AYVLAYSVIMLNTDAHNPMVKNKMSADDFIRNNRGIDDGKDLPEEFMRSLYERISKNEIKM---KEDDLVPQQKQSA 813

Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and Sec7 domain containing) is an guanine nucleotide exchange factor for ADP ribosylation factor 6 (ARF6), which is involved in membrane recycling. EFA6 has four structurally related polypeptides: EFA6A, EFA6B, EFA6C and EFA6D. It consists of a N-terminal proline rich region (PR), a SEC7 domain, a PH domain, a PR, a coiled-coil region, and a C-terminal PR. The EFA6 PH domain regulates its association with the plasma membrane. EFA6 activates Arf6 through its Sec7 catalytic domain and modulates this activity through its C-terminal domain, which rearranges the actin cytoskeleton in fibroblastic cell lines. 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 49116160  772 DPTVPTYKQGILARKMHQDADGKKTPWGKRGWKMFHTLLRGMVLYFLKqGEDHCLEGesLVGQMVDEPVGVHHSLATPAT 851
Cdd:cd13295    1 DPNAVEYKKGYLMRKCCADPDGKKTPFGKRGWKMFYATLKGLVLYLHK-DEYGCKKA--LRYESLRNAISVHHSLATKAT 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 49116160  852 HYTKKPHVFQLRTADWRLYLFQAPTAKEMSSWIARINLAAATHSAPPFP 900
Cdd:cd13295   78 DYTKKPHVFRLRTADWREYLFQASDTKEMQSWIEAINLVAAAFSAPPLP 126

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49116160     590 NLASRLYRLEGFRKSEVAAYLQKNNDFSRAVAEEYLSFFQFGGQSLDRALRSFLQALVLSGETQERERILYQFSRRFHHC 669
Cdd:smart00222   39 DVADFLSKNEGLNKKAIGDYLGEHDEFNRLVLHAFVDLFDFSAKDLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCEC 118

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 49116160     670 NPGIF--PSVDSVHTLTCAIMLLNTDLHGQNIGKSMSCQEFITNLNGLRDGGNFPKELLKALYWSIRSEKL 738
Cdd:smart00222  119 NPGVFskANADAAYTLAYSLIMLNTDLHNPNVKKKMTLEDFIKNVRGSNDGEDLPREFLEELYDSIKNNEI 189

ARF guanine nucleotide exchange factor (ARF-GEF); Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49116160   600 GFRKSEVAAYLQKNNDFSRAVAEEYLSFFQFGGQSLDRALRSFLQALVLSGETQERERILYQFSRRFHHCNPGIFPSVDS 679
Cdd:PLN03076  660 GLNKTLIGDYLGEREDLSLKVMHAYVDSFDFQGMEFDEAIRAFLQGFRLPGEAQKIDRIMEKFAERYCKCNPKAFSSADT 739

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 49116160   680 VHTLTCAIMLLNTDLHGQNIGKSMSCQEFITNLNGLRDGGNFPKELLKALYWSIRSEKLEWavdEEDTARPEKAQPS 756
Cdd:PLN03076  740 AYVLAYSVIMLNTDAHNPMVKNKMSADDFIRNNRGIDDGKDLPEEFMRSLYERISKNEIKM---KEDDLVPQQKQSA 813

ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with a RhoGAP domain. These proteins functions as a GTPase-activating protein (GAP) for RHOA and CDC42. ARHGAP21 controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. It is recruited to the Golgi by to GTPase, ARF1, through its PH domain and its helical motif. It is also required for CTNNA1 recruitment to adherens junctions. ARHGAP21 and it related proteins all contains a PH domain and a RhoGAP domain. Some of the members have additional N-terminal domains including PDZ, SH3, and SPEC. The ARHGAP21 PH domain interacts with the GTPbound forms of both ARF1 and ARF6 ARF-binding domain/ArfBD. The members here include: ARHGAP15, ARHGAP21, and ARHGAP23. 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 49116160  778 YKQGILarKMHQDADGKKTPWGKRGWKMFHTLLRGMVLYFLKQgedhclEGESLVGQMVDE----PVGVHHSLATPATHY 853
Cdd:cd01253    1 AREGWL--HYKQIVTDKGKRVSDRSWKQAWAVLRGHSLYLYKD------KREQTPALSIELgseqRISIRGCIVDIAYSY 72

                         90       100       110
                 ....*....|....*....|....*....|....
gi 49116160  854 TKKPHVFQLRTADWRLYLFQAPTAKEMSSWIARI 887
Cdd:cd01253   73 TKRKHVFRLTTSDFSEYLFQAEDRDDMLGWIKAI 106

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49116160    794 KKTPWGKRGWKMFHTLLRGMVLYFLKqgEDHCLEGESLVG-------QMVDepvgvhhslaTPATHYTKKPHVFQLRTAD 866
Cdd:pfam00169    9 KKGGGKKKSWKKRYFVLFDGSLLYYK--DDKSGKSKEPKGsislsgcEVVE----------VVASDSPKRKFCFELRTGE 76

                           90       100
                   ....*....|....*....|....*....
gi 49116160    867 W---RLYLFQAPTAKEMSSWIARINLAAA 892
Cdd:pfam00169   77 RtgkRTYLLQAESEEERKDWIKAIQSAIR 105

T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; Tiam1 activates Rac GTPases to induce membrane ruffling and cell motility while Tiam2 (also called STEF (SIF (still life) and Tiam1 like-exchange factor) contributes to neurite growth. Tiam1/2 are Dbl-family of GEFs that possess a Dbl(DH) domain with a PH domain in tandem. DH-PH domain catalyzes the GDP/GTP exchange reaction in the GTPase cycle and facillitating the switch between inactive GDP-bound and active GTP-bound states. Tiam1/2 possess two PH domains, which are often referred to as PHn and PHc domains. The DH-PH tandem domain is made up of the PHc domain while the PHn is part of a novel N-terminal PHCCEx domain which is made up of the PHn domain, a coiled coil region(CC), and an extra region (Ex). PHCCEx mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. The PH domain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. CC and Ex form a positively charged surface for protein binding. There are 2 motifs in Tiam1/2-interacting proteins that bind to the PHCCEx domain: Motif-I in CD44, ephrinBs, and the NMDA receptor and Motif-II in Par3 and JIP2.Neither of these fall in the PHn 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 49116160  777 TYKQGILARK--MHQDADGKKTPWGKRGWKMFHTLLRGMVLYFLKQGEDHCLEGESLVGQMVDepvgVHHSLATPATHYT 854
Cdd:cd01230    3 VRKAGWLSVKnfLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALF----VEGSIVQAVPEHP 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 49116160  855 KKPHVFQLRTADWRLYLFQAPTAKEMSSWIARINLAAAT 893
Cdd:cd01230   79 KKDFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACAS 117

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 49116160  800 KRG-----WK-MFHTLLRGMVLYFlKQGEDHCLEGE-SLVGQmvdepvgvhhSLATPATHYTKKPHVFQLRTADWRLYLF 872
Cdd:cd13301   11 KKGhvvnnWKaRWFVLKEDGLEYY-KKKTDSSPKGMiPLKGC----------TITSPCLEYGKRPLVFKLTTAKGQEHFF 79

                         90
                 ....*....|....*...
gi 49116160  873 QAPTAKEMSSWIARINLA 890
Cdd:cd13301   80 QACSREERDAWAKDITKA 97

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 49116160  839 PVGVHHSLATpaTHYTKKPHVFQLRTADwRLYLFQAPTAKEMSSWIARINLA 890
Cdd:cd13255   50 DLTDIHTCTE--VQLKKHDNTFGIVTPA-RTFYVQADSKAEMESWISAINLA 98