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Conserved domains on  [gi|1370480670|ref|XP_024307703|]
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fermitin family homolog 1 isoform X1 [Homo sapiens]

Protein Classification

FERM_F0_KIND1 and PH_fermitin domain-containing protein( domain architecture ID 13019957)

protein containing domains FERM_F0_KIND1, FERM_F1_KIND1, PH_fermitin, and FERM_C_fermitin

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_fermitin cd01237
Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin ...
370-493 4.53e-73

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.


:

Pssm-ID: 269943  Cd Length: 125  Bit Score: 231.51  E-value: 4.53e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 370 PKLADNLKLFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQGEPLEKLNLRGCEVVPDVNVAGRKFGIKLLIPVADGMN 449
Cdd:cd01237     1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNGAPIQQINLKGCEVTPDVNVSQQKFCIKLLVPSPEGMS 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1370480670 450 EMYLRCDHENQYAQWMAACMLASKGKTMADSSYQPEVLNILSFL 493
Cdd:cd01237    81 EVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFL 124
FERM_F0_KIND1 cd17180
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-1 (KIND1) ...
11-94 1.86e-58

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.


:

Pssm-ID: 340700  Cd Length: 84  Bit Score: 191.60  E-value: 1.86e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  11 SWELVVRVDHPNEEQQKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:cd17180     1 SWELSVRVDHQNGEEQKEFTLRVSGDLHIGGVMLKLVEQINVAQDWSDYALWWEQKNCWLLKTHWTLDKYGVQADAKLLF 80

                  ....
gi 1370480670  91 TPQH 94
Cdd:cd17180    81 TPQH 84
FERM_C_fermitin cd13205
FERM domain C-lobe of the Fermitin family; Fermitin functions as a mediator of integrin ...
564-655 5.68e-54

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.


:

Pssm-ID: 270026  Cd Length: 91  Bit Score: 179.46  E-value: 5.68e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 564 EFGLTYYLVRFKGSKKDDILGVSYNRLIKIDAATGIPVTTWRFTNIKQWNVNWETRQVVIEFdQNVFTAFTCLSADCKIV 643
Cdd:cd13205     1 EFGITYFIVRFRGSKKEELLGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNWEIREVIIQF-EDENIAFACLSADCKIV 79
                          90
                  ....*....|..
gi 1370480670 644 HEYIGGYIFLST 655
Cdd:cd13205    80 HEFIGGYIFLSM 91
FERM_F1_KIND1 cd17183
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-1 (KIND1) ...
95-275 4.07e-44

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.


:

Pssm-ID: 340703  Cd Length: 93  Bit Score: 153.07  E-value: 4.07e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  95 KMLRLRLPNLKMVRLRVSFSAVVFKAVSDICKILNIRRSEELSLLKPSgdyfkkkkkkdknnkepiiedilnlessptas 174
Cdd:cd17183     1 KLLRLQLPNMKTVRLKVSFSAVVFKAVSDICKTLNIRRSEELSLLKPS-------------------------------- 48
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 175 gssvspglysktmtpiydpingtpasstmtwfsdsplteqncsilafsqppqspeaLADMYQPRSLVDKAKLNAGWLDSS 254
Cdd:cd17183    49 --------------------------------------------------------LAKMYQPRTLLDKAKLNAGWLDSS 72
                         170       180
                  ....*....|....*....|.
gi 1370480670 255 RSLMEQGIQEDEQLLLRFKYY 275
Cdd:cd17183    73 RSLMEQGIQEDDQLLLRFKYY 93
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
250-343 2.19e-19

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.


:

Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 86.97  E-value: 2.19e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  250 WLDSSRSLMEQGIQ-EDEQLLLRFKYYSFFDLNPKYDAVRINQLYEQARWAILLEEIDCTEEEMLIFAALQYHISKLSLS 328
Cdd:smart00295  55 WLDPAKTLLDQDVKsEPLTLYFRVKFYPPDPNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYD 134
                           90
                   ....*....|....*
gi 1370480670  329 AETQDFAGESEVDEI 343
Cdd:smart00295 135 EELHDLRGELSLKRF 149
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
453-570 6.72e-15

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


:

Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 71.15  E-value: 6.72e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 453 LRCDHENqyAQWMAACMLASKGKTMADSSYQPEVLNILSFLRMKNRNSasqvasslenmdmnpecfvsprcakrHKSKQL 532
Cdd:pfam00373  28 LPCSEEE--ALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRK--------------------------MKSKEL 79
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1370480670 533 AARILEAHQNVAQMPLVEAKLRFIQAWQSLPEFGLTYY 570
Cdd:pfam00373  80 EKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
 
Name Accession Description Interval E-value
PH_fermitin cd01237
Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin ...
370-493 4.53e-73

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.


Pssm-ID: 269943  Cd Length: 125  Bit Score: 231.51  E-value: 4.53e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 370 PKLADNLKLFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQGEPLEKLNLRGCEVVPDVNVAGRKFGIKLLIPVADGMN 449
Cdd:cd01237     1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNGAPIQQINLKGCEVTPDVNVSQQKFCIKLLVPSPEGMS 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1370480670 450 EMYLRCDHENQYAQWMAACMLASKGKTMADSSYQPEVLNILSFL 493
Cdd:cd01237    81 EVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFL 124
FERM_F0_KIND1 cd17180
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-1 (KIND1) ...
11-94 1.86e-58

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.


Pssm-ID: 340700  Cd Length: 84  Bit Score: 191.60  E-value: 1.86e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  11 SWELVVRVDHPNEEQQKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:cd17180     1 SWELSVRVDHQNGEEQKEFTLRVSGDLHIGGVMLKLVEQINVAQDWSDYALWWEQKNCWLLKTHWTLDKYGVQADAKLLF 80

                  ....
gi 1370480670  91 TPQH 94
Cdd:cd17180    81 TPQH 84
FERM_C_fermitin cd13205
FERM domain C-lobe of the Fermitin family; Fermitin functions as a mediator of integrin ...
564-655 5.68e-54

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.


Pssm-ID: 270026  Cd Length: 91  Bit Score: 179.46  E-value: 5.68e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 564 EFGLTYYLVRFKGSKKDDILGVSYNRLIKIDAATGIPVTTWRFTNIKQWNVNWETRQVVIEFdQNVFTAFTCLSADCKIV 643
Cdd:cd13205     1 EFGITYFIVRFRGSKKEELLGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNWEIREVIIQF-EDENIAFACLSADCKIV 79
                          90
                  ....*....|..
gi 1370480670 644 HEYIGGYIFLST 655
Cdd:cd13205    80 HEFIGGYIFLSM 91
FERM_F1_KIND1 cd17183
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-1 (KIND1) ...
95-275 4.07e-44

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.


Pssm-ID: 340703  Cd Length: 93  Bit Score: 153.07  E-value: 4.07e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  95 KMLRLRLPNLKMVRLRVSFSAVVFKAVSDICKILNIRRSEELSLLKPSgdyfkkkkkkdknnkepiiedilnlessptas 174
Cdd:cd17183     1 KLLRLQLPNMKTVRLKVSFSAVVFKAVSDICKTLNIRRSEELSLLKPS-------------------------------- 48
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 175 gssvspglysktmtpiydpingtpasstmtwfsdsplteqncsilafsqppqspeaLADMYQPRSLVDKAKLNAGWLDSS 254
Cdd:cd17183    49 --------------------------------------------------------LAKMYQPRTLLDKAKLNAGWLDSS 72
                         170       180
                  ....*....|....*....|.
gi 1370480670 255 RSLMEQGIQEDEQLLLRFKYY 275
Cdd:cd17183    73 RSLMEQGIQEDDQLLLRFKYY 93
Kindlin_2_N pfam18124
Kindlin-2 N-terminal domain; This is the N-terminal domain (K2-N) of Kindlin-2 protein present ...
11-95 3.25e-39

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.


Pssm-ID: 465660  Cd Length: 89  Bit Score: 139.31  E-value: 3.25e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  11 SWELVVRVDHPNEEQQKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:pfam18124   5 SWELKITVTDMSIKKEVEIPVRVTGDLHIGGVMLKLVESLDITKDWSDHALWWPQACKWLDKTGQTLDKYGVQADAVLLY 84

                  ....*
gi 1370480670  91 TPQHK 95
Cdd:pfam18124  85 TPKHK 89
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
250-343 2.19e-19

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.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 86.97  E-value: 2.19e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  250 WLDSSRSLMEQGIQ-EDEQLLLRFKYYSFFDLNPKYDAVRINQLYEQARWAILLEEIDCTEEEMLIFAALQYHISKLSLS 328
Cdd:smart00295  55 WLDPAKTLLDQDVKsEPLTLYFRVKFYPPDPNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYD 134
                           90
                   ....*....|....*
gi 1370480670  329 AETQDFAGESEVDEI 343
Cdd:smart00295 135 EELHDLRGELSLKRF 149
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
453-570 6.72e-15

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


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 71.15  E-value: 6.72e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 453 LRCDHENqyAQWMAACMLASKGKTMADSSYQPEVLNILSFLRMKNRNSasqvasslenmdmnpecfvsprcakrHKSKQL 532
Cdd:pfam00373  28 LPCSEEE--ALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRK--------------------------MKSKEL 79
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1370480670 533 AARILEAHQNVAQMPLVEAKLRFIQAWQSLPEFGLTYY 570
Cdd:pfam00373  80 EKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
279-347 9.49e-12

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


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 62.29  E-value: 9.49e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 279 DLNPKY-DAVRINQLYEQARWAILLEEIDCTEEEMLIFAALQYHISKLSlsaeTQDFAGESEVDEIEAAL 347
Cdd:pfam00373   1 DLELLLqDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGD----YQPSSHTSEYLSLESFL 66
PH pfam00169
PH domain; PH stands for pleckstrin homology.
378-473 1.83e-11

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 61.04  E-value: 1.83e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 378 LFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQG-EPLEKLNLRGCEVVPDVNVA--GRKFGIKLLIPVADGMNEMYLR 454
Cdd:pfam00169   7 LLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSGKSkEPKGSISLSGCEVVEVVASDspKRKFCFELRTGERTGKRTYLLQ 86
                          90
                  ....*....|....*....
gi 1370480670 455 CDHENQYAQWMAACMLASK 473
Cdd:pfam00169  87 AESEEERKDWIKAIQSAIR 105
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
378-473 2.06e-08

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.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 52.55  E-value: 2.06e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  378 LFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQG-EPLEKLNLRGCEVVPDVN--VAGRKFGIKLLIPvadGMNEMYLR 454
Cdd:smart00233   7 LYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSyKPKGSIDLSGCTVREAPDpdSSKKPHCFEIKTS---DRKTLLLQ 83
                           90
                   ....*....|....*....
gi 1370480670  455 CDHENQYAQWMAACMLASK 473
Cdd:smart00233  84 AESEEEREKWVEALRKAIA 102
 
Name Accession Description Interval E-value
PH_fermitin cd01237
Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin ...
370-493 4.53e-73

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.


Pssm-ID: 269943  Cd Length: 125  Bit Score: 231.51  E-value: 4.53e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 370 PKLADNLKLFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQGEPLEKLNLRGCEVVPDVNVAGRKFGIKLLIPVADGMN 449
Cdd:cd01237     1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNGAPIQQINLKGCEVTPDVNVSQQKFCIKLLVPSPEGMS 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1370480670 450 EMYLRCDHENQYAQWMAACMLASKGKTMADSSYQPEVLNILSFL 493
Cdd:cd01237    81 EVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFL 124
FERM_F0_KIND1 cd17180
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-1 (KIND1) ...
11-94 1.86e-58

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.


Pssm-ID: 340700  Cd Length: 84  Bit Score: 191.60  E-value: 1.86e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  11 SWELVVRVDHPNEEQQKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:cd17180     1 SWELSVRVDHQNGEEQKEFTLRVSGDLHIGGVMLKLVEQINVAQDWSDYALWWEQKNCWLLKTHWTLDKYGVQADAKLLF 80

                  ....
gi 1370480670  91 TPQH 94
Cdd:cd17180    81 TPQH 84
FERM_C_fermitin cd13205
FERM domain C-lobe of the Fermitin family; Fermitin functions as a mediator of integrin ...
564-655 5.68e-54

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.


Pssm-ID: 270026  Cd Length: 91  Bit Score: 179.46  E-value: 5.68e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 564 EFGLTYYLVRFKGSKKDDILGVSYNRLIKIDAATGIPVTTWRFTNIKQWNVNWETRQVVIEFdQNVFTAFTCLSADCKIV 643
Cdd:cd13205     1 EFGITYFIVRFRGSKKEELLGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNWEIREVIIQF-EDENIAFACLSADCKIV 79
                          90
                  ....*....|..
gi 1370480670 644 HEYIGGYIFLST 655
Cdd:cd13205    80 HEFIGGYIFLSM 91
FERM_F1_KIND1 cd17183
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-1 (KIND1) ...
95-275 4.07e-44

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.


Pssm-ID: 340703  Cd Length: 93  Bit Score: 153.07  E-value: 4.07e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  95 KMLRLRLPNLKMVRLRVSFSAVVFKAVSDICKILNIRRSEELSLLKPSgdyfkkkkkkdknnkepiiedilnlessptas 174
Cdd:cd17183     1 KLLRLQLPNMKTVRLKVSFSAVVFKAVSDICKTLNIRRSEELSLLKPS-------------------------------- 48
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 175 gssvspglysktmtpiydpingtpasstmtwfsdsplteqncsilafsqppqspeaLADMYQPRSLVDKAKLNAGWLDSS 254
Cdd:cd17183    49 --------------------------------------------------------LAKMYQPRTLLDKAKLNAGWLDSS 72
                         170       180
                  ....*....|....*....|.
gi 1370480670 255 RSLMEQGIQEDEQLLLRFKYY 275
Cdd:cd17183    73 RSLMEQGIQEDDQLLLRFKYY 93
FERM_F0_kindlins cd17095
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in the kindlin ...
11-94 1.02e-43

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.


Pssm-ID: 340615  Cd Length: 80  Bit Score: 151.30  E-value: 1.02e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  11 SWELVVRVdhpnEEQQKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:cd17095     1 SWELSITV----TDLQIERKLRVTGDLHIGGVMLKLVETLGVAQDWSDHALWWPQKRVWLLKTRSTLDQYGVQADAELHF 76

                  ....
gi 1370480670  91 TPQH 94
Cdd:cd17095    77 TPMH 80
FERM_F0_KIND3 cd17182
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-3 (KIND3) ...
11-94 6.04e-41

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 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 F0 domain.


Pssm-ID: 340702  Cd Length: 83  Bit Score: 143.86  E-value: 6.04e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  11 SWELVVRVDHPNEEQQKdVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:cd17182     1 SWELRVTVEELGPEAEP-VTLRVTGDTHIGGVILKIVEKIMIKQDWSDHALWWEQKRQWLLKTNWTLDKYGVLADARLVF 79

                  ....
gi 1370480670  91 TPQH 94
Cdd:cd17182    80 TPQH 83
Kindlin_2_N pfam18124
Kindlin-2 N-terminal domain; This is the N-terminal domain (K2-N) of Kindlin-2 protein present ...
11-95 3.25e-39

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.


Pssm-ID: 465660  Cd Length: 89  Bit Score: 139.31  E-value: 3.25e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  11 SWELVVRVDHPNEEQQKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:pfam18124   5 SWELKITVTDMSIKKEVEIPVRVTGDLHIGGVMLKLVESLDITKDWSDHALWWPQACKWLDKTGQTLDKYGVQADAVLLY 84

                  ....*
gi 1370480670  91 TPQHK 95
Cdd:pfam18124  85 TPKHK 89
FERM_F0_KIND2 cd17181
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-2 (KIND2) ...
11-94 1.75e-37

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-2 (KIND2); KIND2, also termed fermitin family homolog 2 (FERMT2), or mitogen-inducible gene 2 protein (MIG-2), or Pleckstrin homology (PH) domain-containing family C member 1, is an adaptor protein that is widely distributed and is particularly abundant in adherent cells. It binds to the integrin beta cytoplasmic tail to promote integrin activation. It promotes carcinogenesis through regulation of cell-cell and cell-extracellular matrix adhesion. In additon, KIND2 plays an important role in cardiac development. KIND2 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.


Pssm-ID: 340701  Cd Length: 80  Bit Score: 134.04  E-value: 1.75e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  11 SWELVVRVDHPNeeqqKDVTLRVSGDLHVGGVMLKLVEQINISQDWSDFALWWEQKHCWLLKTHWTLDKYGVQADAKLLF 90
Cdd:cd17181     1 TWELNVHVTDLN----RDVTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKKTWLLKTHWTLDKYGIQADAKLQF 76

                  ....
gi 1370480670  91 TPQH 94
Cdd:cd17181    77 TPQH 80
FERM_F1_kindlins cd17096
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the kindlin ...
95-275 2.91e-36

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.


Pssm-ID: 340616  Cd Length: 90  Bit Score: 130.86  E-value: 2.91e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  95 KMLRLRLPNLKMVRLRVSFSAVVFKAVSDICKILNIRRSEELSLLKPSgdyfkkkkkkdknnkepiiedilnlessptas 174
Cdd:cd17096     1 KTLRIQLPDLQYLDLRVDFSVKVFNAVVDLCKELGIRHPEELSLLRPP-------------------------------- 48
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 175 gssvspglysktmtpiydpingtpasstmtwfsdsplteqncsilafsqppqspealadMYQPRSLVDKAKLNAGWLDSS 254
Cdd:cd17096    49 -----------------------------------------------------------LYRPKSLVDKARLNSGWLDSS 69
                         170       180
                  ....*....|....*....|.
gi 1370480670 255 RSLMEQGIQEDEQLLLRFKYY 275
Cdd:cd17096    70 RSLMEQGVRENDTLLLRFKYY 90
FERM_F1_KIND2 cd17184
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-2 (KIND2) ...
95-275 1.38e-30

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-2 (KIND2); KIND2, also termed fermitin family homolog 2 (FERMT2), or mitogen-inducible gene 2 protein (MIG-2), or Pleckstrin homology (PH) domain-containing family C member 1, is an adaptor protein that is widely distributed and is particularly abundant in adherent cells. It binds to the integrin beta cytoplasmic tail to promote integrin activation. It promotes carcinogenesis through regulation of cell-cell and cell-extracellular matrix adhesion. KIND2 also plays an important role in cardiac development. KIND2 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.


Pssm-ID: 340704  Cd Length: 101  Bit Score: 115.50  E-value: 1.38e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  95 KMLRLRLPNLKMVRLRVSFSAVVFKAVSDICKILNIRRSEELSLLKPSGDyfkkkkkkdknnkepiiedilnlessptas 174
Cdd:cd17184     1 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLRKPRD------------------------------ 50
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 175 gssvspglysktmtpiydpingtpasstmtwfsdsplteqncsilafsqpPQSPEALADMYQPRSLVDKAKLNAGWLDSS 254
Cdd:cd17184    51 --------------------------------------------------PTKKKKLAKMYKPQSLLDKAKINQGWLDSS 80
                         170       180
                  ....*....|....*....|.
gi 1370480670 255 RSLMEQGIQEDEQLLLRFKYY 275
Cdd:cd17184    81 RSLMEQDVKENEALLLRFKYY 101
FERM_F1_KIND3 cd17185
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-3 (KIND3) ...
95-275 3.88e-23

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.


Pssm-ID: 340705  Cd Length: 91  Bit Score: 93.78  E-value: 3.88e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  95 KMLRLRLPNLKMVRLRVSFSAVVFKAVSDICKILNIRRSEELSLLKPsgdyfkkkkkkdknnkepiiedilnlessptas 174
Cdd:cd17185     1 KPVILSLPNRRSLRIRACFSSPVFRAVAGICRVLSIRHPEELSLLRA--------------------------------- 47
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 175 gssvspglysktmtpiydpingtpasstmtwfsdsplteqncsilafsqppqspealADMYQPRSLVDKAKLNAGWLDSS 254
Cdd:cd17185    48 ---------------------------------------------------------PKLYRPSSVTDKTQIHSRWLDSS 70
                         170       180
                  ....*....|....*....|.
gi 1370480670 255 RSLMEQGIQEDEQLLLRFKYY 275
Cdd:cd17185    71 RSLMQQGVQEGDRLWLRFKYY 91
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
250-343 2.19e-19

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.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 86.97  E-value: 2.19e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  250 WLDSSRSLMEQGIQ-EDEQLLLRFKYYSFFDLNPKYDAVRINQLYEQARWAILLEEIDCTEEEMLIFAALQYHISKLSLS 328
Cdd:smart00295  55 WLDPAKTLLDQDVKsEPLTLYFRVKFYPPDPNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYD 134
                           90
                   ....*....|....*
gi 1370480670  329 AETQDFAGESEVDEI 343
Cdd:smart00295 135 EELHDLRGELSLKRF 149
FERM_C-lobe cd00836
FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N ...
566-653 2.73e-15

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.


Pssm-ID: 275389  Cd Length: 93  Bit Score: 71.64  E-value: 2.73e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 566 GLTYYLVRFKGSKK-DDILGVSYNRLIKIDAATGIPVTTWRFTNIKQWNVNW-ETRQVVIEF-DQNVFTAFTCLSADCKI 642
Cdd:cd00836     1 GVEFFPVKDKSKKGsPIILGVNPEGISVYDELTGQPLVLFPWPNIKKISFSGaKKFTIVVADeDKQSKLLFQTPSRQAKE 80
                          90
                  ....*....|.
gi 1370480670 643 VHEYIGGYIFL 653
Cdd:cd00836    81 IWKLIVGYHRF 91
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
453-570 6.72e-15

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


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 71.15  E-value: 6.72e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 453 LRCDHENqyAQWMAACMLASKGKTMADSSYQPEVLNILSFLRMKNRNSasqvasslenmdmnpecfvsprcakrHKSKQL 532
Cdd:pfam00373  28 LPCSEEE--ALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRK--------------------------MKSKEL 79
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1370480670 533 AARILEAHQNVAQMPLVEAKLRFIQAWQSLPEFGLTYY 570
Cdd:pfam00373  80 EKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
279-347 9.49e-12

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


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 62.29  E-value: 9.49e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 279 DLNPKY-DAVRINQLYEQARWAILLEEIDCTEEEMLIFAALQYHISKLSlsaeTQDFAGESEVDEIEAAL 347
Cdd:pfam00373   1 DLELLLqDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGD----YQPSSHTSEYLSLESFL 66
PH pfam00169
PH domain; PH stands for pleckstrin homology.
378-473 1.83e-11

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 61.04  E-value: 1.83e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 378 LFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQG-EPLEKLNLRGCEVVPDVNVA--GRKFGIKLLIPVADGMNEMYLR 454
Cdd:pfam00169   7 LLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSGKSkEPKGSISLSGCEVVEVVASDspKRKFCFELRTGERTGKRTYLLQ 86
                          90
                  ....*....|....*....
gi 1370480670 455 CDHENQYAQWMAACMLASK 473
Cdd:pfam00169  87 AESEEERKDWIKAIQSAIR 105
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
378-473 2.06e-08

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.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 52.55  E-value: 2.06e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  378 LFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQG-EPLEKLNLRGCEVVPDVN--VAGRKFGIKLLIPvadGMNEMYLR 454
Cdd:smart00233   7 LYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSyKPKGSIDLSGCTVREAPDpdSSKKPHCFEIKTS---DRKTLLLQ 83
                           90
                   ....*....|....*....
gi 1370480670  455 CDHENQYAQWMAACMLASK 473
Cdd:smart00233  84 AESEEEREKWVEALRKAIA 102
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
378-468 1.43e-07

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.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 49.85  E-value: 1.43e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 378 LFRPKKLLPKAFKQYWFIFKDTSIAYFKNKELEQGEPLEKLNLRGCEVVPDVNVAGRKFGIKLLIPvadGMNEMYLRCDH 457
Cdd:cd00821     5 LLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTP---DGRTYYLQADS 81
                          90
                  ....*....|.
gi 1370480670 458 ENQYAQWMAAC 468
Cdd:cd00821    82 EEERQEWLKAL 92
FERM_F0_F1 cd01765
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain and F1 sub-domain, found ...
14-94 1.65e-06

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.


Pssm-ID: 340464  Cd Length: 80  Bit Score: 46.43  E-value: 1.65e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670  14 LVVRVDHPNeeqQKDVTLRVSGDLHVGGVMLKLVEQINIsQDWSDFALWWEQ---KHCWLLKtHWTLDKYGVQ-ADAKLL 89
Cdd:cd01765     1 ISCRVRLLD---GTELTLEVSKKATGQELFDKVCEKLNL-LEKDYFGLFYEDndgQKHWLDL-DKKISKQLKRsGPYQFY 75

                  ....*
gi 1370480670  90 FTPQH 94
Cdd:cd01765    76 FRVKF 80
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
390-472 1.68e-05

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.


Pssm-ID: 270126  Cd Length: 97  Bit Score: 43.90  E-value: 1.68e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 390 KQYWFIFKDTSIAYFKNKELEQGEPLEKLNLRGCEVVPDVNVAGRKFGIKLLIPvaDGMNEMYLRCDHENQYAQWMAACM 469
Cdd:cd13316    17 KTRYFVLKGTRLYYLKSENDDKEKGLIDLTGHRVVPDDSNSPFRGSYGFKLVPP--AVPKVHYFAVDEKEELREWMKALM 94

                  ...
gi 1370480670 470 LAS 472
Cdd:cd13316    95 KAT 97
FERM_F1_TLN cd17090
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Talin and ...
249-274 1.14e-04

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.


Pssm-ID: 340610  Cd Length: 111  Bit Score: 41.94  E-value: 1.14e-04
                          10        20
                  ....*....|....*....|....*.
gi 1370480670 249 GWLDSSRSLMEQGIQEDEQLLLRFKY 274
Cdd:cd17090    86 NWLDHDQTLREQGVDEDETLLLRRKF 111
FERM_F1_TLN2 cd17174
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Talin-2 (TLN2); ...
243-274 5.19e-04

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Talin-2 (TLN2); TLN2 is a cytoskeletal protein that plays an important role in cell adhesion and recycling of synaptic vesicles. TLN2 is required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions. TLN2 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.


Pssm-ID: 340694  Cd Length: 112  Bit Score: 40.02  E-value: 5.19e-04
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1370480670 243 KAKLNA----GWLDSSRSLMEQGIQEDEQLLLRFKY 274
Cdd:cd17174    77 KAKLHTdddlNWLDHSRTFREQGVDENETLLLRRKF 112
FERM_F1_TLN1 cd17173
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Talin-1 (TLN1); ...
250-274 1.28e-03

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.


Pssm-ID: 340693  Cd Length: 112  Bit Score: 38.93  E-value: 1.28e-03
                          10        20
                  ....*....|....*....|....*
gi 1370480670 250 WLDSSRSLMEQGIQEDEQLLLRFKY 274
Cdd:cd17173    88 WLDHGRTLREQGVEEHETLLLRRKF 112
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
387-467 2.38e-03

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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.


Pssm-ID: 241446  Cd Length: 103  Bit Score: 38.06  E-value: 2.38e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370480670 387 KAFKQYWFIFKDTSIAYFKNKELEQGEPLEKLNLRGCEVVPDVNvAGRKFGIkllIPVADGMNEMYLRCDHENQYAQWMA 466
Cdd:cd13292    16 KGYKTRWFVLEDGVLSYYRHQDDEGSACRGSINMKNARLVSDPS-EKLRFEV---SSKTSGSPKWYLKANHPVEAARWIQ 91

                  .
gi 1370480670 467 A 467
Cdd:cd13292    92 A 92
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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