Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are 3 members of the AFAP family of adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. AFAP1 is a cSrc binding partner and actin cross-linking protein. AFAP1L1 is thought to play a similar role to AFAP1 in terms of being an actin cross-linking protein, but it preferentially binds to cortactin and not cSrc, thereby playing a role in invadosome formation. AFAP1L2 is a cSrc binding protein, but does not bind to actin filaments. AFAP1L2 acts as an intermediary between the RET/PTC kinase and PI-3kinase pathway in the thyroid. The AFAPs share a similar structure of a SH3 binding motif, 3 SH2 binding motifs, 2 PH domains, a coiled-coil region corresponding to the AFAP1 leucine zipper, and an actin binding domain. The amino terminal PH1 domain of AFAP1 has been known to function in intra-molecular regulation of AFAP1. In addition, the PH1 domain is a binding partner for PKCa and phospholipids. This cd is the first PH domain of AFAP. 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 226437595 210 SEEASMHLVRECRICAFLLRKKRFGQWAKQLTVIREDQLLCYKSSKDRQPHLRLALDTCSIIYVPKDSRHKRHELRFTQG 289
Cdd:cd13306    1 SEEASMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSVIYVPKDGRRKKHELKFTPP 80

                         90       100
                 ....*....|....*....|....*..
gi 226437595 290 ATEVLVLALQSREQAEEWLKVIREVSK 316
Cdd:cd13306   81 GAEALVLAVQSKEQAEQWLKVIREVSS 107

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 226437595  635 TIRTELIALRQEKRELKEAIRSSPGAKLKALEEAVATLEAQCRAKEERRIDLELKLVAVKERLQQSLAG 703
Cdd:COG4913   313 RLEARLDALREELDELEAQIRGNGGDRLEQLEREIERLERELEERERRRARLEALLAALGLPLPASAEE 381

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are 3 members of the AFAP family of adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. AFAP1 is a cSrc binding partner and actin cross-linking protein. AFAP1L1 is thought to play a similar role to AFAP1 in terms of being an actin cross-linking protein, but it preferentially binds to cortactin and not cSrc, thereby playing a role in invadosome formation. AFAP1L2 is a cSrc binding protein, but does not bind to actin filaments. AFAP1L2 acts as an intermediary between the RET/PTC kinase and PI-3kinase pathway in the thyroid. The AFAPs share a similar structure of a SH3 binding motif, 3 SH2 binding motifs, 2 PH domains, a coiled-coil region corresponding to the AFAP1 leucine zipper, and an actin binding domain. The amino terminal PH1 domain of AFAP1 has been known to function in intra-molecular regulation of AFAP1. In addition, the PH1 domain is a binding partner for PKCa and phospholipids. This cd is the first PH domain of AFAP. 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 226437595 210 SEEASMHLVRECRICAFLLRKKRFGQWAKQLTVIREDQLLCYKSSKDRQPHLRLALDTCSIIYVPKDSRHKRHELRFTQG 289
Cdd:cd13306    1 SEEASMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSVIYVPKDGRRKKHELKFTPP 80

                         90       100
                 ....*....|....*....|....*..
gi 226437595 290 ATEVLVLALQSREQAEEWLKVIREVSK 316
Cdd:cd13306   81 GAEALVLAVQSKEQAEQWLKVIREVSS 107

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 226437595   419 VPCCGYLNVLV---NQGWKERWCRLKCNTLYFHKDHMDLR--THVNAIALQGCEV---APGFGPRHPFAFRILRNRQEVA 490
Cdd:smart00233   1 VIKEGWLYKKSgggKKSWKKRYFVLFNSTLLYYKSKKDKKsyKPKGSIDLSGCTVreaPDPDSSKKPHCFEIKTSDRKTL 80

                           90
                   ....*....|....
gi 226437595   491 ILEASCSEDMGRWL 504
Cdd:smart00233  81 LLQAESEEEREKWV 94

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226437595  421 CCGYLNVLVNQ---GWKERWCRLKCNTLYFHKDHMDLRTH--VNAIALQGCEVAPGFGPR---HPFAFRIL---RNRQEV 489
Cdd:pfam00169   3 KEGWLLKKGGGkkkSWKKRYFVLFDGSLLYYKDDKSGKSKepKGSISLSGCEVVEVVASDspkRKFCFELRtgeRTGKRT 82

                          90
                  ....*....|....*
gi 226437595  490 AILEASCSEDMGRWL 504
Cdd:pfam00169  83 YLLQAESEEERKDWI 97

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 226437595  635 TIRTELIALRQEKRELKEAIRSSPGAKLKALEEAVATLEAQCRAKEERRIDLELKLVAVKERLQQSLAG 703
Cdd:COG4913   313 RLEARLDALREELDELEAQIRGNGGDRLEQLEREIERLERELEERERRRARLEALLAALGLPLPASAEE 381

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 1; There are 3 members of the AFAP family of adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. AFAP1 is a cSrc binding partner and actin cross-linking protein. AFAP1L1 is thought to play a similar role to AFAP1 in terms of being an actin cross-linking protein, but it preferentially binds to cortactin and not cSrc, thereby playing a role in invadosome formation. AFAP1L2 is a cSrc binding protein, but does not bind to actin filaments. AFAP1L2 acts as an intermediary between the RET/PTC kinase and PI-3kinase pathway in the thyroid. The AFAPs share a similar structure of a SH3 binding motif, 3 SH2 binding motifs, 2 PH domains, a coiled-coil region corresponding to the AFAP1 leucine zipper, and an actin binding domain. The amino terminal PH1 domain of AFAP1 has been known to function in intra-molecular regulation of AFAP1. In addition, the PH1 domain is a binding partner for PKCa and phospholipids. This cd is the first PH domain of AFAP. 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 226437595 210 SEEASMHLVRECRICAFLLRKKRFGQWAKQLTVIREDQLLCYKSSKDRQPHLRLALDTCSIIYVPKDSRHKRHELRFTQG 289
Cdd:cd13306    1 SEEASMELVKDARICAFLLRKKRFGQWAKQLCVIKDNRLLCYKSSKDQQPQLELPLLGCSVIYVPKDGRRKKHELKFTPP 80

                         90       100
                 ....*....|....*....|....*..
gi 226437595 290 ATEVLVLALQSREQAEEWLKVIREVSK 316
Cdd:cd13306   81 GAEALVLAVQSKEQAEQWLKVIREVSS 107

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 226437595   419 VPCCGYLNVLV---NQGWKERWCRLKCNTLYFHKDHMDLR--THVNAIALQGCEV---APGFGPRHPFAFRILRNRQEVA 490
Cdd:smart00233   1 VIKEGWLYKKSgggKKSWKKRYFVLFNSTLLYYKSKKDKKsyKPKGSIDLSGCTVreaPDPDSSKKPHCFEIKTSDRKTL 80

                           90
                   ....*....|....
gi 226437595   491 ILEASCSEDMGRWL 504
Cdd:smart00233  81 LLQAESEEEREKWV 94

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 226437595 421 CCGYLNVLVNQ---GWKERWCRLKCNTLYFHKDHMDLR-THVNAIALQG-CEVAPGFGPRHPFAFRILRNRQEVAILEAS 495
Cdd:cd00821    1 KEGYLLKRGGGglkSWKKRWFVLFEGVLLYYKSKKDSSyKPKGSIPLSGiLEVEEVSPKERPHCFELVTPDGRTYYLQAD 80

                         90
                 ....*....|..
gi 226437595 496 CSEDMGRWLGLL 507
Cdd:cd00821   81 SEEERQEWLKAL 92

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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 226437595 430 NQGWKERWCRLKCNTLYFHK--DHMDLRTHVNAIALQGCEVAPGFGPRHPFAFRI--LRNRQEVAILEASCSEDMGRWLG 505
Cdd:cd13258   33 SEVFKERWFKLKGNLLFYFRtnEFGDCSEPIGAIVLENCRVQMEEITEKPFAFSIvfNDEPEKKYIFSCRSEEQCEQWIE 112

                 ..
gi 226437595 506 LL 507
Cdd:cd13258  113 AL 114

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from insects, spiders, mollusks, and nematodes. 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 226437595 421 CCGYL-----NVLVNQGWKERWCRLKCNTLYFHKDHMDLRTHVnAIALQG--CEVAPGFGPRhPFAFRILRNrQEVAILE 493
Cdd:cd13326    1 YQGWLyqrrrKGKGGGKWAKRWFVLKGSNLYGFRSQESTKADC-VIFLPGftVSPAPEVKSR-KYAFKVYHT-GTVFYFA 77

                         90
                 ....*....|....
gi 226437595 494 ASCSEDMGRWLGLL 507
Cdd:cd13326   78 AESQEDMKKWLDLL 91

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226437595 225 AFLLRK-KRFGQWAKQLTVIREDQLLCYKSSKDRQPHLRLALD---TCSIIyvpKDSRHKRHELRFTQgaTEVLVLALQS 300
Cdd:cd13298   10 GYLLKRsRKTKNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSellAVAPL---KDKKRKNVFGIYTP--SKNLHFRATS 84

                         90
                 ....*....|....*
gi 226437595 301 REQAEEWLKVIREVS 315
Cdd:cd13298   85 EKDANEWVEALREEF 99

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226437595 417 EEVPCCGYLNvlvNQG-----WKERWCRLKCNTLYFHKDHMDLRtHVNAIALQGCEVAP-GFGPRHP--FAFRIL----- 483
Cdd:cd13263    1 ERPIKSGWLK---KQGsivknWQQRWFVLRGDQLYYYKDEDDTK-PQGTIPLPGNKVKEvPFNPEEPgkFLFEIIpgggg 76

                         90       100       110
                 ....*....|....*....|....*....|....
gi 226437595 484 ---RNRQEVAILEASCSEDMGRWLGLLLVEMGSR 514
Cdd:cd13263   77 drmTSNHDSYLLMANSQAEMEEWVKVIRRVIGSP 110

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; There are 3 members of the AFAP family of adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. AFAP1 is a cSrc binding partner and actin cross-linking protein. AFAP1L1 is thought to play a similar role to AFAP1 in terms of being an actin cross-linking protein, but it preferentially binds to cortactin and not cSrc, thereby playing a role in invadosome formation. AFAP1L2 is a cSrc binding protein, but does not bind to actin filaments. AFAP1L2 acts as an intermediary between the RET/PTC kinase and PI-3kinase pathway in the thyroid. The AFAPs share a similar structure of a SH3 binding motif, 3 SH2 binding motifs, 2 PH domains, a coiled-coil region corresponding to the AFAP1 leucine zipper, and an actin binding domain. This cd is the second PH domain of AFAP. 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 226437595 234 GQWAKQLTVIREDQLLCYKS-SKDRQPHLRLALDTCSIIYVPkDSRHKrHELRFTQGATEVLVLALQSREQAEEWLKVIR 312
Cdd:cd13307   14 QQWRSRWCCVKDGQLHFYQDrNKTKSPQQSLPLHGCEVVPGP-DPKHP-YSFRILRNGEEVAALEASSSEDMGRWLGVLL 91

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. 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 226437595 422 CGYLNVLVNQG-----WKERW---CRLKCnTLYFHKDHMDlRTHVNAIALQGC--EVAPgfgPRHPFAFRIlRNRQEVAI 491
Cdd:cd01265    3 CGYLNKLETRGlglkgWKRRWfvlDESKC-QLYYYRSPQD-ATPLGSIDLSGAafSYDP---EAEPGQFEI-HTPGRVHI 76

                         90
                 ....*....|...
gi 226437595 492 LEASCSEDMGRWL 504
Cdd:cd01265   77 LKASTRQAMLYWL 89