Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin inside-out signalling. The recruitment of Fermitin proteins and Talin to the membrane mediates the terminal event of integrin signalling, via interaction with integrin beta subunits. Fermatin has FERM domain interrupted with a pleckstrin homology (PH) domain. Fermitin family homologs (Fermt1, 2, and 3, also known as Kindlins) are each encoded by a different gene. In mammalian studies, Fermt1 is generally expressed in epithelial cells, Fermt2 is expressed inmuscle tissues, and Fermt3 is expressed in hematopoietic lineages. Specifically Fermt2 is expressed in smooth and striated muscle tissues in mice and in the somites (a trunk muscle precursor) and neural crest in Xenopus embryos. As such it has been proposed that Fermt2 plays a role in cardiomyocyte and neural crest differentiation. Expression of mammalian Fermt3 is associated with hematopoietic lineages: the anterior ventral blood islands, vitelline veins, and early myeloid cells. In Xenopus embryos this expression, also include the notochord and cement gland. 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 7294024  408 PELSDYLRYLKPQRFTLRGYKRYYFTYRDLHLHLFKNAEDSRRvAPAISINLKGCEVTPDVNLSQGKYAIRLEV-SPDGg 486
Cdd:cd01237   1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNG-APIQQINLKGCEVTPDVNVSQQKFCIKLLVpSPEG- 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 7294024  487 hgiNSEVWVRCENEQQYAKWMAACRLAAKGRSLADSSYESEVDSILSLLQ 536
Cdd:cd01237  79 ---MSEVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFLS 125

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in the kindlin family; The kindlin family is composed of kindlin-1, 2 and 3, which are FERM domain-containing adaptor molecules that interact with the cytoplasmic component of integrins and regulate cell-matrix connections. Kindlins belong to the 4.1- ezrin-ridixin-moesin (FERM) domain containing protein family. They contain F1, F2 and F3 subdomains that typify FERM family members, and these subdomains are preceded by an N-terminal F0 subdomain. Both F0 and F1 domains have similar ubiquitin-like folds. This family corresponds to the F0 domain. In addition, a distinctive feature of kindlins is the insertion of a pleckstrin homology (PH) subdomain into the F2 subdomain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7294024    8 SWNLRIFITDLALEKTMRVRGDQHIGGIMLQLVDPEN-PKDWSDHALWWPARNVWLSRTKLTLDQCGVQADSLLHFTPMH 86
Cdd:cd17095   1 SWELSITVTDLQIERKLRVTGDLHIGGVMLKLVETLGvAQDWSDHALWWPQKRVWLLKTRSTLDQYGVQADAELHFTPMH 80

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 7294024     259 VRALQLRPK---SLVEKARLNV--GWLDSSLSIMEQG-IREYDTLCLRFKYFTFFDLNPKCDQVRINQLYEQAKWSVLNE 332
Cdd:smart00295  30 CRKLGIRESeyfGLQFEDPDEDlrHWLDPAKTLLDQDvKSEPLTLYFRVKFYPPDPNQLKEDPTRLNLLYLQVRNDILEG 109

                           90
                   ....*....|....*....
gi 7294024     333 ELDCTEEESLMFAALQFQV 351
Cdd:smart00295 110 RLPCPEEEALLLAALALQA 128

Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin inside-out signalling. The recruitment of Fermitin proteins and Talin to the membrane mediates the terminal event of integrin signalling, via interaction with integrin beta subunits. Fermatin has FERM domain interrupted with a pleckstrin homology (PH) domain. Fermitin family homologs (Fermt1, 2, and 3, also known as Kindlins) are each encoded by a different gene. In mammalian studies, Fermt1 is generally expressed in epithelial cells, Fermt2 is expressed inmuscle tissues, and Fermt3 is expressed in hematopoietic lineages. Specifically Fermt2 is expressed in smooth and striated muscle tissues in mice and in the somites (a trunk muscle precursor) and neural crest in Xenopus embryos. As such it has been proposed that Fermt2 plays a role in cardiomyocyte and neural crest differentiation. Expression of mammalian Fermt3 is associated with hematopoietic lineages: the anterior ventral blood islands, vitelline veins, and early myeloid cells. In Xenopus embryos this expression, also include the notochord and cement gland. 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 7294024  408 PELSDYLRYLKPQRFTLRGYKRYYFTYRDLHLHLFKNAEDSRRvAPAISINLKGCEVTPDVNLSQGKYAIRLEV-SPDGg 486
Cdd:cd01237   1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNG-APIQQINLKGCEVTPDVNVSQQKFCIKLLVpSPEG- 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 7294024  487 hgiNSEVWVRCENEQQYAKWMAACRLAAKGRSLADSSYESEVDSILSLLQ 536
Cdd:cd01237  79 ---MSEVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFLS 125

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in the kindlin family; The kindlin family is composed of kindlin-1, 2 and 3, which are FERM domain-containing adaptor molecules that interact with the cytoplasmic component of integrins and regulate cell-matrix connections. Kindlins belong to the 4.1- ezrin-ridixin-moesin (FERM) domain containing protein family. They contain F1, F2 and F3 subdomains that typify FERM family members, and these subdomains are preceded by an N-terminal F0 subdomain. Both F0 and F1 domains have similar ubiquitin-like folds. This family corresponds to the F0 domain. In addition, a distinctive feature of kindlins is the insertion of a pleckstrin homology (PH) subdomain into the F2 subdomain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7294024    8 SWNLRIFITDLALEKTMRVRGDQHIGGIMLQLVDPEN-PKDWSDHALWWPARNVWLSRTKLTLDQCGVQADSLLHFTPMH 86
Cdd:cd17095   1 SWELSITVTDLQIERKLRVTGDLHIGGVMLKLVETLGvAQDWSDHALWWPQKRVWLLKTRSTLDQYGVQADAELHFTPMH 80

Kindlin-2 N-terminal domain; This is the N-terminal domain (K2-N) of Kindlin-2 protein present in Homo sapiens. Kindlin-2 is a regulator for heterodimeric integrin adhesion receptors promotes integrin activation. Activation depends on binding of the N-terminal domain to the integrin beta cytoplasmic tail (CT), which disrupts the receptors association with alpha-CT and triggers the conformational transitions in the receptor. K2-N contains a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5)-bisphosphate (PIP2). K2-N is also very similar to the homologous kindlin-1 F0.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7294024      4 VGENSWNLRIFITDLALEKTM----RVRGDQHIGGIMLQLVDP-ENPKDWSDHALWWPARNVWLSRTKLTLDQCGVQADS 78
Cdd:pfam18124   1 YADGSWELKITVTDMSIKKEVeipvRVTGDLHIGGVMLKLVESlDITKDWSDHALWWPQACKWLDKTGQTLDKYGVQADA 80

                  ....*....
gi 7294024     79 LLHFTPMHK 87
Cdd:pfam18124  81 VLLYTPKHK 89

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 7294024    314 DQVRINQLYEQAKWSVLNEELDCTEEESLMFAALQFQVNHHvDHTP 359
Cdd:pfam00373   8 DEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFG-DYQP 52

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 7294024     408 PELSDYLRYLKPQRFtlRGYKRYYFTYRDLHLHLFKNAEDSRRVAPAISINLKGCEVTPDVNLSQGKYAIRLEVSPDGGH 487
Cdd:smart00233   1 VIKEGWLYKKSGGGK--KSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDRK 78

                           90       100
                   ....*....|....*....|....*...
gi 7294024     488 ginsEVWVRCENEQQYAKWMAACRLAAK 515
Cdd:smart00233  79 ----TLLLQAESEEEREKWVEALRKAIA 102

FERM domain B-lobe; 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 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, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                        10        20        30
                ....*....|....*....|....*....|....
gi 7294024  318 INQLYEQAKWSVLNEELDCTEEESLMFAALQFQV 351
Cdd:cd14473   2 RYLLYLQVKRDILEGRLPCSEETAALLAALALQA 35

Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin inside-out signalling. The recruitment of Fermitin proteins and Talin to the membrane mediates the terminal event of integrin signalling, via interaction with integrin beta subunits. Fermatin has FERM domain interrupted with a pleckstrin homology (PH) domain. Fermitin family homologs (Fermt1, 2, and 3, also known as Kindlins) are each encoded by a different gene. In mammalian studies, Fermt1 is generally expressed in epithelial cells, Fermt2 is expressed inmuscle tissues, and Fermt3 is expressed in hematopoietic lineages. Specifically Fermt2 is expressed in smooth and striated muscle tissues in mice and in the somites (a trunk muscle precursor) and neural crest in Xenopus embryos. As such it has been proposed that Fermt2 plays a role in cardiomyocyte and neural crest differentiation. Expression of mammalian Fermt3 is associated with hematopoietic lineages: the anterior ventral blood islands, vitelline veins, and early myeloid cells. In Xenopus embryos this expression, also include the notochord and cement gland. 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 7294024  408 PELSDYLRYLKPQRFTLRGYKRYYFTYRDLHLHLFKNAEDSRRvAPAISINLKGCEVTPDVNLSQGKYAIRLEV-SPDGg 486
Cdd:cd01237   1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNG-APIQQINLKGCEVTPDVNVSQQKFCIKLLVpSPEG- 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 7294024  487 hgiNSEVWVRCENEQQYAKWMAACRLAAKGRSLADSSYESEVDSILSLLQ 536
Cdd:cd01237  79 ---MSEVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFLS 125

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in the kindlin family; The kindlin family is composed of kindlin-1, 2 and 3, which are FERM domain-containing adaptor molecules that interact with the cytoplasmic component of integrins and regulate cell-matrix connections. Kindlins belong to the 4.1- ezrin-ridixin-moesin (FERM) domain containing protein family. They contain F1, F2 and F3 subdomains that typify FERM family members, and these subdomains are preceded by an N-terminal F0 subdomain. Both F0 and F1 domains have similar ubiquitin-like folds. This family corresponds to the F0 domain. In addition, a distinctive feature of kindlins is the insertion of a pleckstrin homology (PH) subdomain into the F2 subdomain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7294024    8 SWNLRIFITDLALEKTMRVRGDQHIGGIMLQLVDPEN-PKDWSDHALWWPARNVWLSRTKLTLDQCGVQADSLLHFTPMH 86
Cdd:cd17095   1 SWELSITVTDLQIERKLRVTGDLHIGGVMLKLVETLGvAQDWSDHALWWPQKRVWLLKTRSTLDQYGVQADAELHFTPMH 80

Kindlin-2 N-terminal domain; This is the N-terminal domain (K2-N) of Kindlin-2 protein present in Homo sapiens. Kindlin-2 is a regulator for heterodimeric integrin adhesion receptors promotes integrin activation. Activation depends on binding of the N-terminal domain to the integrin beta cytoplasmic tail (CT), which disrupts the receptors association with alpha-CT and triggers the conformational transitions in the receptor. K2-N contains a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5)-bisphosphate (PIP2). K2-N is also very similar to the homologous kindlin-1 F0.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7294024      4 VGENSWNLRIFITDLALEKTM----RVRGDQHIGGIMLQLVDP-ENPKDWSDHALWWPARNVWLSRTKLTLDQCGVQADS 78
Cdd:pfam18124   1 YADGSWELKITVTDMSIKKEVeipvRVTGDLHIGGVMLKLVESlDITKDWSDHALWWPQACKWLDKTGQTLDKYGVQADA 80

                  ....*....
gi 7294024     79 LLHFTPMHK 87
Cdd:pfam18124  81 VLLYTPKHK 89

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-1 (KIND1); KIND1, also termed Kindlerin, or Kindler syndrome protein, or fermitin family homolog 1 (FERMT1), or Unc-112-related protein 1 (URP1), is an integrin-interacting protein that has been implicated in cell adhesion, proliferation, polarity, and motility. It is essential for maintaining the structure of cell-matrix adhesion, such as focal adhesions and podosomes. KIND1 is expressed primarily in epithelial cells. Loss or mutations of KIND1 gene may cause the Kindler syndrome (KS), an autosomal recessive skin disorder with an intriguing progressive phenotype comprising skin blistering, photosensitivity, progressive poikiloderma with extensive skin atrophy, and propensity to skin cancer. KIND1 forms a molecular complex with the key transforming growth factor (TGF)-beta/Smad3 signaling components including type I TGFbeta receptor (TbetaRI), Smad3 and Smad anchor for receptor activation (SARA) to control the activation of TGF-beta/Smad3 signaling pathway. KIND1 consists of an atypical FERM domain that is made up of F1, F2 and F3 domains, as well as an N-terminal region, which precedes the FERM domain and has been referred to as the F0 domain. This family corresponds to the F0 domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7294024    8 SWNLRIFIT----DLALEKTMRVRGDQHIGGIMLQLVDPEN-PKDWSDHALWWPARNVWLSRTKLTLDQCGVQADSLLHF 82
Cdd:cd17180   1 SWELSVRVDhqngEEQKEFTLRVSGDLHIGGVMLKLVEQINvAQDWSDYALWWEQKNCWLLKTHWTLDKYGVQADAKLLF 80

                ....
gi 7294024   83 TPMH 86
Cdd:cd17180  81 TPQH 84

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 7294024     259 VRALQLRPK---SLVEKARLNV--GWLDSSLSIMEQG-IREYDTLCLRFKYFTFFDLNPKCDQVRINQLYEQAKWSVLNE 332
Cdd:smart00295  30 CRKLGIRESeyfGLQFEDPDEDlrHWLDPAKTLLDQDvKSEPLTLYFRVKFYPPDPNQLKEDPTRLNLLYLQVRNDILEG 109

                           90
                   ....*....|....*....
gi 7294024     333 ELDCTEEESLMFAALQFQV 351
Cdd:smart00295 110 RLPCPEEEALLLAALALQA 128

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-1 (KIND1); KIND1, also termed Kindlerin, or Kindler syndrome protein, or fermitin family homolog 1 (FERMT1), or Unc-112-related protein 1 (URP1), is an integrin-interacting protein that has been implicated in cell adhesion, proliferation, polarity, and motility. It is essential for maintaining the structure of cell-matrix adhesion, such as focal adhesions and podosomes. KIND1 is expressed primarily in epithelial cells. Loss or mutations of KIND1 gene may cause the Kindler syndrome (KS), an autosomal recessive skin disorder with an intriguing progressive phenotype comprising skin blistering, photosensitivity, progressive poikiloderma with extensive skin atrophy, and propensity to skin cancer. KIND1 forms a molecular complex with the key transforming growth factor (TGF)-beta/Smad3 signaling components including type I TGFbeta receptor (TbetaRI), Smad3 and Smad anchor for receptor activation (SARA) to control the activation of TGF-beta/Smad3 signaling pathway. KIND1 consists of an atypical FERM domain that is made up of F1, F2 and F3 domains, as well as an N-terminal region, which precedes the FERM domain and has been referred to as the F0 domain. This family corresponds to the F1 domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 7294024  265 RPKSLVEKARLNVGWLDSSLSIMEQGIREYDTLCLRFKYF 304
Cdd:cd17183  54 QPRTLLDKAKLNAGWLDSSRSLMEQGIQEDDQLLLRFKYY 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7294024    507 MAACRLAAKGRSLADSSYESEVDSILSLLQMQrpahgvhvnidprsveavdylspkIIRKLSNKAV-QRILEAHANVREL 585
Cdd:pfam00373  38 LAALQLQAEFGDYQPSSHTSEYLSLESFLPKQ------------------------LLRKMKSKELeKRVLEAHKNLRGL 93

                          90       100
                  ....*....|....*....|....
gi 7294024    586 NALDSKLKYIQAWRSLPDFGVSLF 609
Cdd:pfam00373  94 SAEEAKLKYLQIAQSLPTYGVEFF 117

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 7294024     408 PELSDYLRYLKPQRFtlRGYKRYYFTYRDLHLHLFKNAEDSRRVAPAISINLKGCEVTPDVNLSQGKYAIRLEVSPDGGH 487
Cdd:smart00233   1 VIKEGWLYKKSGGGK--KSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSDRK 78

                           90       100
                   ....*....|....*....|....*...
gi 7294024     488 ginsEVWVRCENEQQYAKWMAACRLAAK 515
Cdd:smart00233  79 ----TLLLQAESEEEREKWVEALRKAIA 102

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7294024    408 PELSDYLRYLKPQRFTlrGYKRYYFTYRDLHLHLFKNAEDSRRVAPAISINLKGCEVTPDVNLSQG--KYAIRLEVSPDG 485
Cdd:pfam00169   1 VVKEGWLLKKGGGKKK--SWKKRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVVEVVASDSPkrKFCFELRTGERT 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 7294024    486 GhgiNSEVWVRCENEQQYAKWMAACRLAAK 515
Cdd:pfam00169  79 G---KRTYLLQAESEEERKDWIKAIQSAIR 105

FERM domain B-lobe; 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 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, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                        10        20        30
                ....*....|....*....|....*....|....
gi 7294024  318 INQLYEQAKWSVLNEELDCTEEESLMFAALQFQV 351
Cdd:cd14473   2 RYLLYLQVKRDILEGRLPCSEETAALLAALALQA 35

Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally redundant and important for cell growth with Boi mutants displaying defects in bud formation and in the maintenance of cell polarity.They appear to be linked to Rho-type GTPase, Cdc42 and Rho3. Boi1 and Boi2 display two-hybrid interactions with the GTP-bound ("active") form of Cdc42, while Rho3 can suppress of the lethality caused by deletion of Boi1 and Boi2. These findings suggest that Boi1 and Boi2 are targets of Cdc42 that promote cell growth in a manner that is regulated by Rho3. Boi proteins contain a N-terminal SH3 domain, followed by a SAM (sterile alpha motif) domain, a proline-rich region, which mediates binding to the second SH3 domain of Bem1, and C-terminal PH domain. The PH domain is essential for its function in cell growth and is important for localization to the bud, while the SH3 domain is needed for localization to the neck. 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 7294024  412 DYLRYLKPQRFTLRGYKRYYFTYRDLHLHLFKNAEDSRRVApaiSINLKGCEVTPD--VNLSQGKYAIRLeVSPDGG--H 487
Cdd:cd13316   1 DHSGWMKKRGERYGTWKTRYFVLKGTRLYYLKSENDDKEKG---LIDLTGHRVVPDdsNSPFRGSYGFKL-VPPAVPkvH 76

                        90       100
                ....*....|....*....|..
gi 7294024  488 ginsevWVRCENEQQYAKWMAA 509
Cdd:cd13316  77 ------YFAVDEKEELREWMKA 92

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7294024  416 YLKPQRFTLRGYKRYYFTYRDLHLHLFKNAEDSRrvaPAISINLKGCEV-----TPDvnlSQGKYAirLEVSPDGG---H 487
Cdd:cd13263   8 WLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTK---PQGTIPLPGNKVkevpfNPE---EPGKFL--FEIIPGGGgdrM 79

                        90       100       110
                ....*....|....*....|....*....|..
gi 7294024  488 GINSEVWVRCENEQQ-YAKWMAACRLAAKGRS 518
Cdd:cd13263  80 TSNHDSYLLMANSQAeMEEWVKVIRRVIGSPF 111

Slm1 Pleckstrin homology (PH) domain; Slm1 is a component of the target of rapamycin complex 2 (TORC2) signaling pathway. It plays a role in the regulation of actin organization and is a target of sphingolipid signaling during the heat shock response. Slm1 contains a single PH domain that binds PtdIns(4,5)P2, PtdIns(4)P, and dihydrosphingosine 1-phosphate (DHS-1P). Slm1 possesses two binding sites for anionic lipids. The non-canonical binding site of the PH domain of Slm1 is used for ligand binding, and it is proposed that beta-spectrin, Tiam1 and ArhGAP9 also have this type of phosphoinositide binding site. 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 7294024  424 LRGYKRYYFTY-RDLHLHLFKNAEDSRRVAPAISINLKGCEVTPDVNLSQGKYAIRLEVSPDGGHGINSE-VWV-RCENE 500
Cdd:cd13311  16 LKSYSKGYYVLtPAGYLHEFKSSDRKKDPAPEMSLYLPECKIGAPSNKGSKSHKFILKGKDVGSGKFHRGhEWVfKAESH 95

                        90
                ....*....|....*
gi 7294024  501 QQYAKWMAACRLAAK 515
Cdd:cd13311  96 EEMMAWWEDIKELTK 110