FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 572 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 651
Cdd:cd17179     1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                          90       100
                  ....*....|....*....|...
gi 1907123512 652 QQPGKCEGSRTVRLTYKNRLYFS 674
Cdd:cd17179    81 QHPGKCEGTRTVRLTYKNRLYFS 103

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 158 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLATEKHTYYLTADSPNIL 237
Cdd:cd13282     1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                          90
                  ....*....|....*.
gi 1907123512 238 EEWIKVLQSVLRVQAA 253
Cdd:cd13282    81 DEWIRVIQNVLRRQAS 96

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512  575 IPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRkpAQSGFALFTDDPSGrDLEHCLQGNIKICDIISKWEqaskeqqp 654
Cdd:smart00295   2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR--ESEYFGLQFEDPDE-DLRHWLDPAKTLLDQDVKSE-------- 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512  655 gkcegsrTVRLTYKNRLYFSVQARGETDREKTLLLY-QTNDQIINGLFPLNKDLALEMAALLAQVDIGDFERPFSTPAGP 733
Cdd:smart00295  71 -------PLTLYFRVKFYPPDPNQLKEDPTRLNLLYlQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGE 143

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907123512  734 VtnqckanqtlkqVIERFYPKRYREgcsEEQLRQLYQRLSTKWMALRGHSAADCIRIYLTVARKWPFFGAKLF 806
Cdd:smart00295 144 L------------SLKRFLPKQLLD---SRKLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 572 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 651
Cdd:cd17179     1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                          90       100
                  ....*....|....*....|...
gi 1907123512 652 QQPGKCEGSRTVRLTYKNRLYFS 674
Cdd:cd17179    81 QHPGKCEGTRTVRLTYKNRLYFS 103

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 158 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLATEKHTYYLTADSPNIL 237
Cdd:cd13282     1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                          90
                  ....*....|....*.
gi 1907123512 238 EEWIKVLQSVLRVQAA 253
Cdd:cd13282    81 DEWIRVIQNVLRRQAS 96

MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also present in 3 other myosins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 455 AQSALQVCLTHPELQNEICCQLIKQTRRRQlqNQPGPLQGWQLLALCVGLFLPHHPFLWLLQLHLQRNADSR-TEFGKYA 533
Cdd:pfam00784   1 AQNILQKGLKRPELRDEIYCQLIKQTTNNP--KPESLLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDPsREVGKYA 78

                          90       100
                  ....*....|....*....|....*..
gi 1907123512 534 IYCQRCVERTQQNGDREARPSRMEILS 560
Cdd:pfam00784  79 QFCLKRLKRTLKNGGRKYPPSREEIEA 105

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 156 LEKSGYLLKMS-VRVKTWKRRWFVLKGGELLYYKSPSDVI-RKPQGHIELSASCSILRGDNKQT---------VQLATEK 224
Cdd:pfam00169   1 VVKEGWLLKKGgGKKKSWKKRYFVLFDGSLLYYKDDKSGKsKEPKGSISLSGCEVVEVVASDSPkrkfcfelrTGERTGK 80

                          90       100
                  ....*....|....*....|....*
gi 1907123512 225 HTYYLTADSPNILEEWIKVLQSVLR 249
Cdd:pfam00169  81 RTYLLQAESEEERKDWIKAIQSAIR 105

FERM central domain; This domain is the central structural domain of the FERM domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 680 ETDREKTLLLYQTNDQIINGLFPLNKDLALEMAALLAQVDIGDFerpfstpagpvtnQCKANQTLKQVIERFYPKRYreg 759
Cdd:pfam00373   7 QDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDY-------------QPSSHTSEYLSLESFLPKQL--- 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1907123512 760 CSEEQLRQLYQRLSTKWMALRGHSAADCIRIYLTVARKWPFFGAKLF 806
Cdd:pfam00373  71 LRKMKSKELEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 256 LCLQPEGKpavKGLLTK---VKHGYSKRvWCMLVGKVLYYFRNQEDKFPLGQLKLWEAKVEevdrSCDSDEDYetrgCYL 332
Cdd:cd13288     3 TCNSPVDK---EGYLWKkgeRNTSYQKR-WFVLKGNLLFYFEKKGDREPLGVIVLEGCTVE----LAEDAEPY----AFA 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1907123512 333 LSTHytiivhpkdqGP---TYLLIGSKHEK-EAWLYHLTVA 369
Cdd:cd13288    71 IRFD----------GPgarSYVLAAENQEDmESWMKALSRA 101

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 1907123512  267 KGLLTKVKHGYS---KRVWCMLVGKVLYYFRN---QEDKFPLGQLKLWEAKVEEVDRSCDSDEDyetrgcyllsthYTII 340
Cdd:smart00233   4 EGWLYKKSGGGKkswKKRYFVLFNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKP------------HCFE 71

                           90       100
                   ....*....|....*....|....*.
gi 1907123512  341 VHPKDQGPTYLLIGSKHEKEAWLYHL 366
Cdd:smart00233  72 IKTSDRKTLLLQAESEEEREKWVEAL 97

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 572 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 651
Cdd:cd17179     1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                          90       100
                  ....*....|....*....|...
gi 1907123512 652 QQPGKCEGSRTVRLTYKNRLYFS 674
Cdd:cd17179    81 QHPGKCEGTRTVRLTYKNRLYFS 103

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Caenorhabditis elegans max-1 and its homologs PLEKHH1 and PLEKHH2; Caenorhabditis elegans max-1 is expressed and functions in motor neurons. MAX-1 protein plays a possible role in netrin-induced axon repulsion by modulating the UNC-5 receptor signaling pathway. PLEKHH1 is critically required in vascular patterning in vertebrate species through acting upstream of the ephrin pathway. PLEKHH2 is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. It is involved in matrix adhesion and actin dynamics. Members in this family all contain two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 572 PFSIPVHFMNGLYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 651
Cdd:cd17094     1 PISIPVHLPNGTYQVVGFDGSTTVEEFLQTLNLELGIRPPSQSGFALFSDDPIGKDIEHCLQPSVKICDVISKWERASRE 80

                          90       100
                  ....*....|....*....|..
gi 1907123512 652 QQPGKCEGSRTVRLTYKNRLYF 673
Cdd:cd17094    81 AHSGKVDSSRVIRLTYKNRLYF 102

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 158 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLATEKHTYYLTADSPNIL 237
Cdd:cd13282     1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                          90
                  ....*....|....*.
gi 1907123512 238 EEWIKVLQSVLRVQAA 253
Cdd:cd13282    81 DEWIRVIQNVLRRQAS 96

MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also present in 3 other myosins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 455 AQSALQVCLTHPELQNEICCQLIKQTRRRQlqNQPGPLQGWQLLALCVGLFLPHHPFLWLLQLHLQRNADSR-TEFGKYA 533
Cdd:pfam00784   1 AQNILQKGLKRPELRDEIYCQLIKQTTNNP--KPESLLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDPsREVGKYA 78

                          90       100
                  ....*....|....*....|....*..
gi 1907123512 534 IYCQRCVERTQQNGDREARPSRMEILS 560
Cdd:pfam00784  79 QFCLKRLKRTLKNGGRKYPPSREEIEA 105

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 1907123512 158 KSGYLLKMS-VRVKTWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSI---LRGDNKQTVQLATEKH-TYYLTAD 232
Cdd:cd00821     1 KEGYLLKRGgGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVeevSPKERPHCFELVTPDGrTYYLQAD 80

                          90
                  ....*....|..
gi 1907123512 233 SPNILEEWIKVL 244
Cdd:cd00821    81 SEEERQEWLKAL 92

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 151 GKNEPLEKSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSD--VIRK-PQGHIELSASCSILRGDNkqTVQLATEKHTY 227
Cdd:cd13255     1 MISEAVLKAGYLEKKGERRKTWKKRWFVLRPTKLAYYKNDKEyrLLRLiDLTDIHTCTEVQLKKHDN--TFGIVTPARTF 78

                          90
                  ....*....|....*..
gi 1907123512 228 YLTADSPNILEEWIKVL 244
Cdd:cd13255    79 YVQADSKAEMESWISAI 95

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 158 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPsDVIR--KPQGHIELSaSCSILRGD----NKQ-TVQLATEKHTYYLT 230
Cdd:cd13276     1 KAGWLEKQGEFIKTWRRRWFVLKQGKLFWFKEP-DVTPysKPRGVIDLS-KCLTVKSAedatNKEnAFELSTPEETFYFI 78

                          90
                  ....*....|.
gi 1907123512 231 ADSPNILEEWI 241
Cdd:cd13276    79 ADNEKEKEEWI 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 158 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASCSILRGDNKQTV---QLATEKHTYYLTADSP 234
Cdd:cd10573     5 KEGYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDT--KPIRVLDLRECSSVQRDYSQGKVncfCLVFPERTFYMYANTE 82

                          90
                  ....*....|....
gi 1907123512 235 NILEEWIKVLQSVL 248
Cdd:cd10573    83 EEADEWVKLLKWKL 96

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 1907123512 158 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASC----------------SILRGDNKQtvQLA 221
Cdd:cd13263     5 KSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDT--KPQGTIPLPGNKvkevpfnpeepgkflfEIIPGGGGD--RMT 80

                          90       100
                  ....*....|....*....|....*..
gi 1907123512 222 TEKHTYYLTADSPNILEEWIKVLQSVL 248
Cdd:cd13263    81 SNHDSYLLMANSQAEMEEWVKVIRRVI 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 1907123512  156 LEKSGYLLKMS-VRVKTWKRRWFVLKGGELLYYKSPSDV-IRKPQGHIELSaSCSI------LRGDNKQTVQLAT-EKHT 226
Cdd:smart00233   1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLS-GCTVreapdpDSSKKPHCFEIKTsDRKT 79

                           90       100
                   ....*....|....*....|...
gi 1907123512  227 YYLTADSPNILEEWIKVLQSVLR 249
Cdd:smart00233  80 LLLQAESEEEREKWVEALRKAIA 102

FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 802 GAKLFFAKPiapSSLGNNCVWLAVHENGLSILEYTSMRLVTSYMYK--GLMTFGGyQEDFMVVVSTQSKDRpteKLLFAM 879
Cdd:cd00836     1 GVEFFPVKD---KSKKGSPIILGVNPEGISVYDELTGQPLVLFPWPniKKISFSG-AKKFTIVVADEDKQS---KLLFQT 73

                          90       100
                  ....*....|....*....|
gi 1907123512 880 AKHKILEITLLIASYINSFH 899
Cdd:cd00836    74 PSRQAKEIWKLIVGYHRFLL 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 157 EKSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIELS------------ASCSILRGD-NKQTVQ---- 219
Cdd:cd01252     4 DREGWLLKLGGRVKSWKRRWFILTDNCLYYFEYTTD--KEPRGIIPLEnlsvrevedkkkPFCFELYSPsNGQVIKackt 81

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1907123512 220 -----LATEKHT-YYLTADSPNILEEWIKVLQSVL 248
Cdd:cd01252    82 dsdgkVVEGNHTvYRISAASEEERDEWIKSIKASI 116

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 1907123512 158 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIELS--ASCSILRGDNKQTV-QLATEKHTYYLTADSP 234
Cdd:cd13298     8 KSGYLLKRSRKTKNWKKRWVVLRPCQLSYYKDEKE--YKLRRVINLSelLAVAPLKDKKRKNVfGIYTPSKNLHFRATSE 85

                          90
                  ....*....|....*
gi 1907123512 235 NILEEWIKVLQSVLR 249
Cdd:cd13298    86 KDANEWVEALREEFR 100

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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 1907123512 155 PLEKSGYLLKMSVRVKTWKRRWFVLKGGE--LLYYKSPSDVirKPQGHIELSaSCSIL--------RGDNKQTVQLATEK 224
Cdd:cd13260     2 GIDKKGYLLKKGGKNKKWKNLYFVLEGKEqhLYFFDNEKRT--KPKGLIDLS-YCSLYpvhdslfgRPNCFQIVVRALNE 78

                          90       100
                  ....*....|....*....|..
gi 1907123512 225 HT-YYLTADSPNILEEWIKVLQ 245
Cdd:cd13260    79 STiTYLCADTAELAQEWMRALR 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 154 EPLEKSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSAS----------------CSILRGDNKQT 217
Cdd:cd13378     1 EGVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEET--KPQGCISLQGSqvnelppnpeepgkhlFEILPGGAGDR 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1907123512 218 VQLATEKHTYYLTADSPNILEEWIKVLQSVL 248
Cdd:cd13378    79 EKVPMNHEAFLLMANSQSDMEDWVKAIRRVI 109

FERM central domain; This domain is the central structural domain of the FERM domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123512 680 ETDREKTLLLYQTNDQIINGLFPLNKDLALEMAALLAQVDIGDFerpfstpagpvtnQCKANQTLKQVIERFYPKRYreg 759
Cdd:pfam00373   7 QDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDY-------------QPSSHTSEYLSLESFLPKQL--- 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1907123512 760 CSEEQLRQLYQRLSTKWMALRGHSAADCIRIYLTVARKWPFFGAKLF 806
Cdd:pfam00373  71 LRKMKSKELEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also called pleckstrin homology domain containing, family B): evt-1 (also called PLEKHB1) and evt-2 (also called PLEKHB2). evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia. evt-2 is widely expressed in both neural and nonneural tissues. Evectins possess a single N-terminal PH domain and a C-terminal hydrophobic region. evt-1 is thought to function as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. It is a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and a susceptibility gene for multiple sclerosis. evt-2 is essential for retrograde endosomal membrane transport from the plasma membrane (PM) to the Golgi. Two membrane trafficking pathways pass through recycling endosomes: a recycling pathway and a retrograde pathway that links the PM to the Golgi/ER. Its PH domain that is unique in that it specifically recognizes phosphatidylserine (PS), but not polyphosphoinositides. PS is an anionic phospholipid class in eukaryotic biomembranes, is highly enriched in the PM, and plays key roles in various physiological processes such as the coagulation cascade, recruitment and activation of signaling molecules, and clearance of apoptotic cells. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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 1907123512 154 EPLEKSGYLLKMSVRVKTWKRRWFVLKG-GELLYYKSPSDviRKPQGHIELSASCSILR 211
Cdd:cd13265     1 MALVKSGWLLRQSTILKRWKKNWFVLYGdGNLVYYEDETR--REVEGRINMPRECRNIR 57

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 1907123512 158 KSGYLLKMSVRVKTWKRRWFVLKGGELLYYKSPSDviRKPQGHIEL---SASCSILRGDNKQTV-QLATEK-HTYYLTAD 232
Cdd:cd13301     5 KEGYLVKKGHVVNNWKARWFVLKEDGLEYYKKKTD--SSPKGMIPLkgcTITSPCLEYGKRPLVfKLTTAKgQEHFFQAC 82