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 116686114 370 PKLADNLKLFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQGEPLEKLNLRGCEVVPDVNVAGRKFGIKLLIPVADGMN 449
Cdd:cd01237    1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNGAPIQQINLKGCEVTPDVNVSQQKFCIKLLVPSPEGMS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 116686114 450 EMYLRCDHENQYAQWMAACMLASKGKTMADSSYQPEVLNILSFL 493
Cdd:cd01237   81 EVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFL 124

FERM domain C-lobe of the Fermitin family; 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. 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). This cd is not included in the C-lobe hierarchy based on its position in the tree. One thing to note is that unlike the other members of the C-lobe hierarchy it contains 2 FERM M domains which might also reflect a difference in its evolutionary history. 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 116686114 564 EFGLTYYLVRFKGSKKDDILGVSYNRLIKIDAATGIPVTTWRFTNIKQWNVNWETRQVVIEFdQNVFTAFTCLSADCKIV 643
Cdd:cd13205    1 EFGITYFIVRFRGSKKEELLGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNWEIREVIIQF-EDENIAFACLSADCKIV 79

                         90
                 ....*....|..
gi 116686114 644 HEYIGGYIFLST 655
Cdd:cd13205   80 HEFIGGYIFLSM 91

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 116686114   250 WLDSSRSLMEQGIQ-EDEQLLLRFKYYSFFDLNPKYDAVRINQLYEQARWAILLEEIDCTEEEMLIFAALQYHISKLSLS 328
Cdd:smart00295  55 WLDPAKTLLDQDVKsEPLTLYFRVKFYPPDPNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYD 134

                           90
                   ....*....|....*
gi 116686114   329 AETQDFAGESEVDEI 343
Cdd:smart00295 135 EELHDLRGELSLKRF 149

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 116686114 370 PKLADNLKLFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQGEPLEKLNLRGCEVVPDVNVAGRKFGIKLLIPVADGMN 449
Cdd:cd01237    1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNGAPIQQINLKGCEVTPDVNVSQQKFCIKLLVPSPEGMS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 116686114 450 EMYLRCDHENQYAQWMAACMLASKGKTMADSSYQPEVLNILSFL 493
Cdd:cd01237   81 EVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFL 124

FERM domain C-lobe of the Fermitin family; 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. 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). This cd is not included in the C-lobe hierarchy based on its position in the tree. One thing to note is that unlike the other members of the C-lobe hierarchy it contains 2 FERM M domains which might also reflect a difference in its evolutionary history. 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 116686114 564 EFGLTYYLVRFKGSKKDDILGVSYNRLIKIDAATGIPVTTWRFTNIKQWNVNWETRQVVIEFdQNVFTAFTCLSADCKIV 643
Cdd:cd13205    1 EFGITYFIVRFRGSKKEELLGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNWEIREVIIQF-EDENIAFACLSADCKIV 79

                         90
                 ....*....|..
gi 116686114 644 HEYIGGYIFLST 655
Cdd:cd13205   80 HEFIGGYIFLSM 91

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 116686114   11 SWELVVRVDHPNEEQQKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:pfam18124   5 SWELKITVTDMSIKKEVEIPVRVTGDLHIGGVMLKLVESLDITKDWSDHALWWPQACKWLDKTGQTLDKYGVQADAVLLY 84

                  ....*
gi 116686114   91 TPQHK 95
Cdd:pfam18124  85 TPKHK 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116686114  453 LRCDHENqyAQWMAACMLASKGKTMADSSYQPEVLNILSFLRMKNRNSasqvasslenmdmnpecfvsprcakrHKSKQL 532
Cdd:pfam00373  28 LPCSEEE--ALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRK--------------------------MKSKEL 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 116686114  533 AARILEAHQNVAQMPLVEAKLRFIQAWQSLPEFGLTYY 570
Cdd:pfam00373  80 EKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116686114  378 LFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQG-EPLEKLNLRGCEVVPDVNVA--GRKFGIKLLIPVADGMNEMYLR 454
Cdd:pfam00169   7 LLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSGKSkEPKGSISLSGCEVVEVVASDspKRKFCFELRTGERTGKRTYLLQ 86

                          90
                  ....*....|....*....
gi 116686114  455 CDHENQYAQWMAACMLASK 473
Cdd:pfam00169  87 AESEEERKDWIKAIQSAIR 105

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 116686114 370 PKLADNLKLFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQGEPLEKLNLRGCEVVPDVNVAGRKFGIKLLIPVADGMN 449
Cdd:cd01237    1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNGAPIQQINLKGCEVTPDVNVSQQKFCIKLLVPSPEGMS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 116686114 450 EMYLRCDHENQYAQWMAACMLASKGKTMADSSYQPEVLNILSFL 493
Cdd:cd01237   81 EVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFL 124

FERM domain C-lobe of the Fermitin family; 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. 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). This cd is not included in the C-lobe hierarchy based on its position in the tree. One thing to note is that unlike the other members of the C-lobe hierarchy it contains 2 FERM M domains which might also reflect a difference in its evolutionary history. 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 116686114 564 EFGLTYYLVRFKGSKKDDILGVSYNRLIKIDAATGIPVTTWRFTNIKQWNVNWETRQVVIEFdQNVFTAFTCLSADCKIV 643
Cdd:cd13205    1 EFGITYFIVRFRGSKKEELLGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNWEIREVIIQF-EDENIAFACLSADCKIV 79

                         90
                 ....*....|..
gi 116686114 644 HEYIGGYIFLST 655
Cdd:cd13205   80 HEFIGGYIFLSM 91

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 116686114  11 SWELVVRVdhpnEEQQKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:cd17095    1 SWELSITV----TDLQIERKLRVTGDLHIGGVMLKLVETLGVAQDWSDHALWWPQKRVWLLKTRSTLDQYGVQADAELHF 76

                 ....
gi 116686114  91 TPQH 94
Cdd:cd17095   77 TPMH 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 116686114   11 SWELVVRVDHPNEEQQKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:pfam18124   5 SWELKITVTDMSIKKEVEIPVRVTGDLHIGGVMLKLVESLDITKDWSDHALWWPQACKWLDKTGQTLDKYGVQADAVLLY 84

                  ....*
gi 116686114   91 TPQHK 95
Cdd:pfam18124  85 TPKHK 89

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 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 F1 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 116686114  95 KMLRLRLPNLKMVRLRVSFSAVVFKAVSDICKILNIRRSEELSLLKPSgdyfkkkkkkdknnkepiiedilnlessptas 174
Cdd:cd17096    1 KTLRIQLPDLQYLDLRVDFSVKVFNAVVDLCKELGIRHPEELSLLRPP-------------------------------- 48

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116686114 175 gssvspglysktmtpiydpingtpasstmtwfsdsplteqncsilafsqppqspealadMYQPRSLVDKAKLNAGWLDSS 254
Cdd:cd17096   49 -----------------------------------------------------------LYRPKSLVDKARLNSGWLDSS 69

                        170       180
                 ....*....|....*....|.
gi 116686114 255 RSLMEQGIQEDEQLLLRFKYY 275
Cdd:cd17096   70 RSLMEQGVRENDTLLLRFKYY 90

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-3 (KIND3); KIND3, also termed fermitin family homolog 3 (FERMT3), or MIG2-like protein, or Unc-112-related protein 2, is an adaptor protein that expressed primarily in hematopoietic cells. It plays a central role in cell adhesion in hematopoietic cells, and also promotes integrin activation, clustering and outside-in signaling. KIND3, together with talin-1, contributes essentially to the activation of beta2-integrins in neutrophils. In addition, KIND3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells. Mutations in the KIND3 gene cause leukocyte adhesion deficiency type III (LAD III), which is characterized by high susceptibility to infections, spontaneous and episodic bleedings, and osteopetrosis. KIND3 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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116686114  95 KMLRLRLPNLKMVRLRVSFSAVVFKAVSDICKILNIRRSEELSLLKPsgdyfkkkkkkdknnkepiiedilnlessptas 174
Cdd:cd17185    1 KPVILSLPNRRSLRIRACFSSPVFRAVAGICRVLSIRHPEELSLLRA--------------------------------- 47

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116686114 175 gssvspglysktmtpiydpingtpasstmtwfsdsplteqncsilafsqppqspealADMYQPRSLVDKAKLNAGWLDSS 254
Cdd:cd17185   48 ---------------------------------------------------------PKLYRPSSVTDKTQIHSRWLDSS 70

                        170       180
                 ....*....|....*....|.
gi 116686114 255 RSLMEQGIQEDEQLLLRFKYY 275
Cdd:cd17185   71 RSLMQQGVQEGDRLWLRFKYY 91

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 116686114 566 GLTYYLVRFKGSKK-DDILGVSYNRLIKIDAATGIPVTTWRFTNIKQWNVNW-ETRQVVIEF-DQNVFTAFTCLSADCKI 642
Cdd:cd00836    1 GVEFFPVKDKSKKGsPIILGVNPEGISVYDELTGQPLVLFPWPNIKKISFSGaKKFTIVVADeDKQSKLLFQTPSRQAKE 80

                         90
                 ....*....|.
gi 116686114 643 VHEYIGGYIFL 653
Cdd:cd00836   81 IWKLIVGYHRF 91

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116686114  279 DLNPKY-DAVRINQLYEQARWAILLEEIDCTEEEMLIFAALQYHISKLSlsaeTQDFAGESEVDEIEAAL 347
Cdd:pfam00373   1 DLELLLqDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGD----YQPSSHTSEYLSLESFL 66

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 116686114   378 LFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQG-EPLEKLNLRGCEVVPDVN--VAGRKFGIKLLIPvadGMNEMYLR 454
Cdd:smart00233   7 LYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSyKPKGSIDLSGCTVREAPDpdSSKKPHCFEIKTS---DRKTLLLQ 83

                           90
                   ....*....|....*....
gi 116686114   455 CDHENQYAQWMAACMLASK 473
Cdd:smart00233  84 AESEEEREKWVEALRKAIA 102

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain and F1 sub-domain, found in FERM (Four.1/Ezrin/Radixin/Moesin) family proteins; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain is present at the N-terminus of a large and diverse group of proteins that mediate linkage of the cytoskeleton to the plasma membrane. FERM-containing proteins are ubiquitous components of the cytocortex and are involved in cell transport, cell structure and signaling functions. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N), which is structurally similar to ubiquitin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116686114  14 LVVRVDHPNeeqQKDVTLRVSGDLHVGGVMLKLVEQINIsQDWSDFALWWEQ---KHCWLLKtHWTLDKYGVQ-ADAKLL 89
Cdd:cd01765    1 ISCRVRLLD---GTELTLEVSKKATGQELFDKVCEKLNL-LEKDYFGLFYEDndgQKHWLDL-DKKISKQLKRsGPYQFY 75

                 ....*
gi 116686114  90 FTPQH 94
Cdd:cd01765   76 FRVKF 80

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Talin and similar proteins; Talin is a cytoskeletal protein that activates integrins and couples them to cytoskeletal actin. Talin consists of an N-terminal head and a C-terminal rod. The talin head harbors a FERM (Band 4.1, ezrin, radixin, moesin) domain made up of F1, F2 and F3 domains, as well as an N-terminal region that precedes the FERM domain and has been referred to as the F0 domain. Both F0 and F1 domains have similar ubiquitin-like folds. This family corresponds to the F0 domain that is joined to the F1 domain in a novel fixed orientation by an extensive charged interface. It is required for maximal integrin-activation, by interacting with other FA components; no binding partner has yet been found for it.

                         10        20
                 ....*....|....*....|....*.
gi 116686114 249 GWLDSSRSLMEQGIQEDEQLLLRFKY 274
Cdd:cd17090   86 NWLDHDQTLREQGVDEDETLLLRRKF 111

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Talin-1 (TLN1); TLN1 is a cytoskeletal protein that plays a pivotal role in regulating the activity of the integrin family of cell adhesion proteins by coupling them to F-actin. It functions as a focal adhesion protein involved in the attachment of the bacterium. It binds to multiple adhesion molecules, including integrins, vinculin, focal adhesion kinase (FAK), and actin. TLN1 also plays an essential role in integrin activation. TLN1 interacts with the hepatitis B virus (HBV) accessory protein X (HBx), which induces the degradation of TLN1. It also acts as an adaptor protein that regulates leukocyte function-associated antigen-1 (LFA-1) affinity. In addition, TLN1 is required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions. TLN1 consists of an N-terminal head and a C-terminal rod. The talin head harbors a FERM (Band 4.1, ezrin, radixin, moesin) domain made up of F1, F2 and F3 domains, as well as an N-terminal region that precedes the FERM domain and has been referred to as the F0 domain. Both F0 and F1 domains have similar ubiquitin-like folds. This family corresponds to the F1 domain.

                         10        20
                 ....*....|....*....|....*
gi 116686114 250 WLDSSRSLMEQGIQEDEQLLLRFKY 274
Cdd:cd17173   88 WLDHGRTLREQGVEEHETLLLRRKF 112