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Conserved domains on  [gi|578825430|ref|XP_006720073|]
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fermitin family homolog 2 isoform X3 [Homo sapiens]

Protein Classification

FRMD7 family protein( domain architecture ID 13019995)

FRMD7 family protein similar to Homo sapiens FERM domain-containing protein 7 (FRMD7) that plays a role in neurite development

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 ...
 373-497 8.27e-87

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: 268.10  E-value: 8.27e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 373 PELADYIKVFKPKKLTLKGYKQYWCTFKDTSISCYKSKEESSGTPAHQMNLRGCEVTPDVNISGQKFNIKLLIPVAEGMN 452
Cdd:cd01237    1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNGAPIQQINLKGCEVTPDVNVSQQKFCIKLLVPSPEGMS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 578825430 453 EIWLRCDNEKQYAHWMAACRLASKGKTMADSSYNLEVQNILSFLK 497
Cdd:cd01237   81 EVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFLS 125
FERM_F1_KIND2 cd17184
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-2 (KIND2) ...
 97-277 3.43e-55

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: 183.68  E-value: 3.43e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  97 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLKKPRDPTKKKKkklddqsedealelegplitpgsg 176
Cdd:cd17184    1 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLRKPRDPTKKKK------------------------ 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 177 siysspglysktmtptydahdgsplsptsawfgdsalsegnpgilavsqpitspeiLAKMFKPQALLDKAKINQGWLDSS 256
Cdd:cd17184   57 --------------------------------------------------------LAKMYKPQSLLDKAKINQGWLDSS 80

                        170       180
                 ....*....|....*....|.
gi 578825430 257 RSLMEQDVKENEALLLRFKYY 277
Cdd:cd17184   81 RSLMEQDVKENEALLLRFKYY 101
FERM_F0_KIND2 cd17181
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-2 (KIND2) ...
 17-96 3.38e-52

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: 174.87  E-value: 3.38e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  17 TWELSVHVTDLNRDVTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKRTWLLKTHWTLDKYGIQADAKLQFTPQH 96
Cdd:cd17181    1 TWELNVHVTDLNRDVTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKKTWLLKTHWTLDKYGIQADAKLQFTPQH 80
FERM_C_fermitin cd13205
FERM domain C-lobe of the Fermitin family; Fermitin functions as a mediator of integrin ...
 582-673 7.13e-50

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: 168.67  E-value: 7.13e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 582 EFGITHFIARFQGGKKEELIGIAYNRLIRMDASTGDAIKTWRFSNMKQWNVNWEIKMVTVEFADEvRLSFICTEVDCKVV 661
Cdd:cd13205    1 EFGITYFIVRFRGSKKEELLGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNWEIREVIIQFEDE-NIAFACLSADCKIV 79

                         90
                 ....*....|..
gi 578825430 662 HEFIGGYIFLST 673
Cdd:cd13205   80 HEFIGGYIFLSM 91
FERM_M super family cl47539
FERM central domain; This domain is the central structural domain of the FERM domain.
 455-588 8.47e-14

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


The actual alignment was detected with superfamily member pfam00373:

Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 68.06  E-value: 8.47e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  455 WLRCDNEkQYAHwMAACRLASKGKTMADSSYNLEVQNILSFLKMQhlnpdpqlipeqittditpeclvsprYLKKYKNKQ 534
Cdd:pfam00373  27 RLPCSEE-EALL-LAALQLQAEFGDYQPSSHTSEYLSLESFLPKQ--------------------------LLRKMKSKE 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 578825430  535 ekgckkhmpgyirdlITARILEAHQNVAQMSLIEAKMRFIQAWQSLPEFGITHF 588
Cdd:pfam00373  79 ---------------LEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
B41 super family cl33382
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 241-324 5.76e-13

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.


The actual alignment was detected with superfamily member smart00295:

Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 68.09  E-value: 5.76e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430   241 ALLDKAKINQGWLDSSRSLMEQDVK-ENEALLLRFKYYSFFDLNPKYDAIRINQLYEQAKWAILLEEIECTEEEMMMFAA 319
Cdd:smart00295  44 QFEDPDEDLRHWLDPAKTLLDQDVKsEPLTLYFRVKFYPPDPNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAA 123


                   ....*
gi 578825430   320 LQYHI 324
Cdd:smart00295 124 LALQA 128
 
Name Accession Description Interval E-value
PH_fermitin cd01237
Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin ...
 373-497 8.27e-87

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: 268.10  E-value: 8.27e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 373 PELADYIKVFKPKKLTLKGYKQYWCTFKDTSISCYKSKEESSGTPAHQMNLRGCEVTPDVNISGQKFNIKLLIPVAEGMN 452
Cdd:cd01237    1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNGAPIQQINLKGCEVTPDVNVSQQKFCIKLLVPSPEGMS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 578825430 453 EIWLRCDNEKQYAHWMAACRLASKGKTMADSSYNLEVQNILSFLK 497
Cdd:cd01237   81 EVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFLS 125
FERM_F1_KIND2 cd17184
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-2 (KIND2) ...
 97-277 3.43e-55

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: 183.68  E-value: 3.43e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  97 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLKKPRDPTKKKKkklddqsedealelegplitpgsg 176
Cdd:cd17184    1 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLRKPRDPTKKKK------------------------ 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 177 siysspglysktmtptydahdgsplsptsawfgdsalsegnpgilavsqpitspeiLAKMFKPQALLDKAKINQGWLDSS 256
Cdd:cd17184   57 --------------------------------------------------------LAKMYKPQSLLDKAKINQGWLDSS 80

                        170       180
                 ....*....|....*....|.
gi 578825430 257 RSLMEQDVKENEALLLRFKYY 277
Cdd:cd17184   81 RSLMEQDVKENEALLLRFKYY 101
FERM_F0_KIND2 cd17181
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-2 (KIND2) ...
 17-96 3.38e-52

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: 174.87  E-value: 3.38e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  17 TWELSVHVTDLNRDVTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKRTWLLKTHWTLDKYGIQADAKLQFTPQH 96
Cdd:cd17181    1 TWELNVHVTDLNRDVTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKKTWLLKTHWTLDKYGIQADAKLQFTPQH 80
FERM_C_fermitin cd13205
FERM domain C-lobe of the Fermitin family; Fermitin functions as a mediator of integrin ...
 582-673 7.13e-50

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: 168.67  E-value: 7.13e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 582 EFGITHFIARFQGGKKEELIGIAYNRLIRMDASTGDAIKTWRFSNMKQWNVNWEIKMVTVEFADEvRLSFICTEVDCKVV 661
Cdd:cd13205    1 EFGITYFIVRFRGSKKEELLGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNWEIREVIIQFEDE-NIAFACLSADCKIV 79

                         90
                 ....*....|..
gi 578825430 662 HEFIGGYIFLST 673
Cdd:cd13205   80 HEFIGGYIFLSM 91
Kindlin_2_N pfam18124
Kindlin-2 N-terminal domain; This is the N-terminal domain (K2-N) of Kindlin-2 protein present ...
 13-97 4.14e-41

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: 144.71  E-value: 4.14e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430   13 YADGTWELSVHVTDLNRD----VTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKRTWLLKTHWTLDKYGIQADA 88
Cdd:pfam18124   1 YADGSWELKITVTDMSIKkeveIPVRVTGDLHIGGVMLKLVESLDITKDWSDHALWWPQACKWLDKTGQTLDKYGVQADA 80


                  ....*....
gi 578825430   89 KLQFTPQHK 97
Cdd:pfam18124  81 VLLYTPKHK 89
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 455-588 8.47e-14

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


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 68.06  E-value: 8.47e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  455 WLRCDNEkQYAHwMAACRLASKGKTMADSSYNLEVQNILSFLKMQhlnpdpqlipeqittditpeclvsprYLKKYKNKQ 534
Cdd:pfam00373  27 RLPCSEE-EALL-LAALQLQAEFGDYQPSSHTSEYLSLESFLPKQ--------------------------LLRKMKSKE 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 578825430  535 ekgckkhmpgyirdlITARILEAHQNVAQMSLIEAKMRFIQAWQSLPEFGITHF 588
Cdd:pfam00373  79 ---------------LEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 241-324 5.76e-13

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: 68.09  E-value: 5.76e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430   241 ALLDKAKINQGWLDSSRSLMEQDVK-ENEALLLRFKYYSFFDLNPKYDAIRINQLYEQAKWAILLEEIECTEEEMMMFAA 319
Cdd:smart00295  44 QFEDPDEDLRHWLDPAKTLLDQDVKsEPLTLYFRVKFYPPDPNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAA 123


                   ....*
gi 578825430   320 LQYHI 324
Cdd:smart00295 124 LALQA 128
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 381-476 1.40e-09

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: 55.63  E-value: 1.40e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430   381 VFKPKKLTLKGYKQYWCTFKDTSISCYKSKEES-SGTPAHQMNLRGCEVTPDVNISGQKFNIKLLIpVAEGMNEIWLRCD 459
Cdd:smart00233   7 LYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEI-KTSDRKTLLLQAE 85

                           90
                   ....*....|....*..
gi 578825430   460 NEKQYAHWMAACRLASK 476
Cdd:smart00233  86 SEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 381-476 1.89e-09

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 55.65  E-value: 1.89e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  381 VFKPKKLTLKGYKQYWCTFKDTSISCYKSK-EESSGTPAHQMNLRGCEVTPDVNIS--GQKFNIKLLIPVAEGMNEIWLR 457
Cdd:pfam00169   7 LLKKGGGKKKSWKKRYFVLFDGSLLYYKDDkSGKSKEPKGSISLSGCEVVEVVASDspKRKFCFELRTGERTGKRTYLLQ 86

                          90
                  ....*....|....*....
gi 578825430  458 CDNEKQYAHWMAACRLASK 476
Cdd:pfam00169  87 AESEEERKDWIKAIQSAIR 105
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 493-588 1.30e-03

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: 40.74  E-value: 1.30e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430   493 LSFLKMQHLNPDPQlipeqITTDITPECLVSPRYLKKYKNKQEKgckkhmpgyiRDLITARILEAHQNVAQMSLIEAKMR 572
Cdd:smart00295 121 LAALALQAEFGDYD-----EELHDLRGELSLKRFLPKQLLDSRK----------LKEWRERIVELHKELIGLSPEEAKLK 185

                           90
                   ....*....|....*.
gi 578825430   573 FIQAWQSLPEFGITHF 588
Cdd:smart00295 186 YLELARKLPTYGVELF 201
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 281-326 1.92e-03

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


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 38.79  E-value: 1.92e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 578825430  281 DLNPKY-DAIRINQLYEQAKWAILLEEIECTEEEMMMFAALQYHINK 326
Cdd:pfam00373   1 DLELLLqDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEF 47
 
Name Accession Description Interval E-value
PH_fermitin cd01237
Fermitin family pleckstrin homology (PH) domain; Fermitin functions as a mediator of integrin ...
 373-497 8.27e-87

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: 268.10  E-value: 8.27e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 373 PELADYIKVFKPKKLTLKGYKQYWCTFKDTSISCYKSKEESSGTPAHQMNLRGCEVTPDVNISGQKFNIKLLIPVAEGMN 452
Cdd:cd01237    1 PELADYLKYFKPKKFTLKGYKRYWFVFKDTHLSYYKSKEESNGAPIQQINLKGCEVTPDVNVSQQKFCIKLLVPSPEGMS 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 578825430 453 EIWLRCDNEKQYAHWMAACRLASKGKTMADSSYNLEVQNILSFLK 497
Cdd:cd01237   81 EVWLRCDNEDQYAKWMAACRLASKGKTMADSSYDSEVSSILAFLS 125
FERM_F1_KIND2 cd17184
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-2 (KIND2) ...
 97-277 3.43e-55

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: 183.68  E-value: 3.43e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  97 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLKKPRDPTKKKKkklddqsedealelegplitpgsg 176
Cdd:cd17184    1 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLRKPRDPTKKKK------------------------ 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 177 siysspglysktmtptydahdgsplsptsawfgdsalsegnpgilavsqpitspeiLAKMFKPQALLDKAKINQGWLDSS 256
Cdd:cd17184   57 --------------------------------------------------------LAKMYKPQSLLDKAKINQGWLDSS 80

                        170       180
                 ....*....|....*....|.
gi 578825430 257 RSLMEQDVKENEALLLRFKYY 277
Cdd:cd17184   81 RSLMEQDVKENEALLLRFKYY 101
FERM_F0_KIND2 cd17181
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-2 (KIND2) ...
 17-96 3.38e-52

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: 174.87  E-value: 3.38e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  17 TWELSVHVTDLNRDVTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKRTWLLKTHWTLDKYGIQADAKLQFTPQH 96
Cdd:cd17181    1 TWELNVHVTDLNRDVTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKKTWLLKTHWTLDKYGIQADAKLQFTPQH 80
FERM_C_fermitin cd13205
FERM domain C-lobe of the Fermitin family; Fermitin functions as a mediator of integrin ...
 582-673 7.13e-50

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: 168.67  E-value: 7.13e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 582 EFGITHFIARFQGGKKEELIGIAYNRLIRMDASTGDAIKTWRFSNMKQWNVNWEIKMVTVEFADEvRLSFICTEVDCKVV 661
Cdd:cd13205    1 EFGITYFIVRFRGSKKEELLGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNWEIREVIIQFEDE-NIAFACLSADCKIV 79

                         90
                 ....*....|..
gi 578825430 662 HEFIGGYIFLST 673
Cdd:cd13205   80 HEFIGGYIFLSM 91
FERM_F0_kindlins cd17095
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in the kindlin ...
 17-96 8.39e-48

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: 162.86  E-value: 8.39e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  17 TWELSVHVTDLNRDVTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKRTWLLKTHWTLDKYGIQADAKLQFTPQH 96
Cdd:cd17095    1 SWELSITVTDLQIERKLRVTGDLHIGGVMLKLVETLGVAQDWSDHALWWPQKRVWLLKTRSTLDQYGVQADAELHFTPMH 80
FERM_F0_KIND3 cd17182
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-3 (KIND3) ...
 17-96 5.18e-42

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: 146.95  E-value: 5.18e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  17 TWELSVHVTDLNRD---VTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKRTWLLKTHWTLDKYGIQADAKLQFT 93
Cdd:cd17182    1 SWELRVTVEELGPEaepVTLRVTGDTHIGGVILKIVEKIMIKQDWSDHALWWEQKRQWLLKTNWTLDKYGVLADARLVFT 80


                 ...
gi 578825430  94 PQH 96
Cdd:cd17182   81 PQH 83
FERM_F0_KIND1 cd17180
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in kindlin-1 (KIND1) ...
 17-96 2.04e-41

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: 145.37  E-value: 2.04e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  17 TWELSVHVT----DLNRDVTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKRTWLLKTHWTLDKYGIQADAKLQF 92
Cdd:cd17180    1 SWELSVRVDhqngEEQKEFTLRVSGDLHIGGVMLKLVEQINVAQDWSDYALWWEQKNCWLLKTHWTLDKYGVQADAKLLF 80


                 ....
gi 578825430  93 TPQH 96
Cdd:cd17180   81 TPQH 84
Kindlin_2_N pfam18124
Kindlin-2 N-terminal domain; This is the N-terminal domain (K2-N) of Kindlin-2 protein present ...
 13-97 4.14e-41

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: 144.71  E-value: 4.14e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430   13 YADGTWELSVHVTDLNRD----VTLRVTGEVHIGGVMLKLVEKLDVKKDWSDHALWWEKKRTWLLKTHWTLDKYGIQADA 88
Cdd:pfam18124   1 YADGSWELKITVTDMSIKkeveIPVRVTGDLHIGGVMLKLVESLDITKDWSDHALWWPQACKWLDKTGQTLDKYGVQADA 80


                  ....*....
gi 578825430   89 KLQFTPQHK 97
Cdd:pfam18124  81 VLLYTPKHK 89
FERM_F1_kindlins cd17096
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the kindlin ...
 97-277 4.62e-37

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: 133.56  E-value: 4.62e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  97 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLkkprdptkkkkkklddqsedealelegplitpgsg 176
Cdd:cd17096    1 KTLRIQLPDLQYLDLRVDFSVKVFNAVVDLCKELGIRHPEELSLL----------------------------------- 45

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 177 siysspglysktmtptydahdgsplsptsawfgdsalsegnpgilavsqpitspeiLAKMFKPQALLDKAKINQGWLDSS 256
Cdd:cd17096   46 --------------------------------------------------------RPPLYRPKSLVDKARLNSGWLDSS 69

                        170       180
                 ....*....|....*....|.
gi 578825430 257 RSLMEQDVKENEALLLRFKYY 277
Cdd:cd17096   70 RSLMEQGVRENDTLLLRFKYY 90
FERM_F1_KIND1 cd17183
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-1 (KIND1) ...
 97-277 2.21e-32

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: 120.33  E-value: 2.21e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  97 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLkkprdptkkkkkklddqsedealelegplitpgsg 176
Cdd:cd17183    1 KLLRLQLPNMKTVRLKVSFSAVVFKAVSDICKTLNIRRSEELSLL----------------------------------- 45

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 177 siysspglysktmtptydahdgsplSPTsawfgdsalsegnpgilavsqpitspeiLAKMFKPQALLDKAKINQGWLDSS 256
Cdd:cd17183   46 -------------------------KPS----------------------------LAKMYQPRTLLDKAKLNAGWLDSS 72

                        170       180
                 ....*....|....*....|.
gi 578825430 257 RSLMEQDVKENEALLLRFKYY 277
Cdd:cd17183   73 RSLMEQGIQEDDQLLLRFKYY 93
FERM_F1_KIND3 cd17185
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in kindlin-3 (KIND3) ...
 97-277 3.00e-21

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: 88.77  E-value: 3.00e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  97 KLLRLQLPNMKYVKVKVNFSDRVFKAVSDICKTFNIRHPEELSLLKKprdptkkkkkklddqsedealelegplitpgsg 176
Cdd:cd17185    1 KPVILSLPNRRSLRIRACFSSPVFRAVAGICRVLSIRHPEELSLLRA--------------------------------- 47

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 177 siysspglysktmtptydahdgsplsptsawfgdsalsegnpgilavsqpitspeilAKMFKPQALLDKAKINQGWLDSS 256
Cdd:cd17185   48 ---------------------------------------------------------PKLYRPSSVTDKTQIHSRWLDSS 70

                        170       180
                 ....*....|....*....|.
gi 578825430 257 RSLMEQDVKENEALLLRFKYY 277
Cdd:cd17185   71 RSLMQQGVQEGDRLWLRFKYY 91
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 455-588 8.47e-14

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


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 68.06  E-value: 8.47e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  455 WLRCDNEkQYAHwMAACRLASKGKTMADSSYNLEVQNILSFLKMQhlnpdpqlipeqittditpeclvsprYLKKYKNKQ 534
Cdd:pfam00373  27 RLPCSEE-EALL-LAALQLQAEFGDYQPSSHTSEYLSLESFLPKQ--------------------------LLRKMKSKE 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 578825430  535 ekgckkhmpgyirdlITARILEAHQNVAQMSLIEAKMRFIQAWQSLPEFGITHF 588
Cdd:pfam00373  79 ---------------LEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 241-324 5.76e-13

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: 68.09  E-value: 5.76e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430   241 ALLDKAKINQGWLDSSRSLMEQDVK-ENEALLLRFKYYSFFDLNPKYDAIRINQLYEQAKWAILLEEIECTEEEMMMFAA 319
Cdd:smart00295  44 QFEDPDEDLRHWLDPAKTLLDQDVKsEPLTLYFRVKFYPPDPNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAA 123


                   ....*
gi 578825430   320 LQYHI 324
Cdd:smart00295 124 LALQA 128
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 381-476 1.40e-09

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: 55.63  E-value: 1.40e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430   381 VFKPKKLTLKGYKQYWCTFKDTSISCYKSKEES-SGTPAHQMNLRGCEVTPDVNISGQKFNIKLLIpVAEGMNEIWLRCD 459
Cdd:smart00233   7 LYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEI-KTSDRKTLLLQAE 85

                           90
                   ....*....|....*..
gi 578825430   460 NEKQYAHWMAACRLASK 476
Cdd:smart00233  86 SEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 381-476 1.89e-09

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 55.65  E-value: 1.89e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430  381 VFKPKKLTLKGYKQYWCTFKDTSISCYKSK-EESSGTPAHQMNLRGCEVTPDVNIS--GQKFNIKLLIPVAEGMNEIWLR 457
Cdd:pfam00169   7 LLKKGGGKKKSWKKRYFVLFDGSLLYYKDDkSGKSKEPKGSISLSGCEVVEVVASDspKRKFCFELRTGERTGKRTYLLQ 86

                          90
                  ....*....|....*....
gi 578825430  458 CDNEKQYAHWMAACRLASK 476
Cdd:pfam00169  87 AESEEERKDWIKAIQSAIR 105
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 381-471 3.37e-08

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: 51.39  E-value: 3.37e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 381 VFKPKKLTLKGYKQYWCTFKDTSISCYKSKEESSGTPAHQMNLRGCEVTPDVNISGQKFNIKLLIPvaeGMNEIWLRCDN 460
Cdd:cd00821    5 LLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTP---DGRTYYLQADS 81

                         90
                 ....*....|.
gi 578825430 461 EKQYAHWMAAC 471
Cdd:cd00821   82 EEERQEWLKAL 92
FERM_C-lobe cd00836
FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N ...
 584-671 1.55e-05

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: 43.90  E-value: 1.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430 584 GITHFIARFQGGKKEELI-GIAYNRLIRMDASTGDAIKTWRFSNMKQWNVNWEiKMVTVEFADEVR---LSFICTEVDCK 659
Cdd:cd00836    1 GVEFFPVKDKSKKGSPIIlGVNPEGISVYDELTGQPLVLFPWPNIKKISFSGA-KKFTIVVADEDKqskLLFQTPSRQAK 79

                         90
                 ....*....|..
gi 578825430 660 VVHEFIGGYIFL 671
Cdd:cd00836   80 EIWKLIVGYHRF 91
FERM_F1_TLN cd17090
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Talin and ...
 251-276 4.57e-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: 40.40  E-value: 4.57e-04
                         10        20
                 ....*....|....*....|....*.
gi 578825430 251 GWLDSSRSLMEQDVKENEALLLRFKY 276
Cdd:cd17090   86 NWLDHDQTLREQGVDEDETLLLRRKF 111
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 493-588 1.30e-03

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: 40.74  E-value: 1.30e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578825430   493 LSFLKMQHLNPDPQlipeqITTDITPECLVSPRYLKKYKNKQEKgckkhmpgyiRDLITARILEAHQNVAQMSLIEAKMR 572
Cdd:smart00295 121 LAALALQAEFGDYD-----EELHDLRGELSLKRFLPKQLLDSRK----------LKEWRERIVELHKELIGLSPEEAKLK 185

                           90
                   ....*....|....*.
gi 578825430   573 FIQAWQSLPEFGITHF 588
Cdd:smart00295 186 YLELARKLPTYGVELF 201
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 281-326 1.92e-03

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


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 38.79  E-value: 1.92e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 578825430  281 DLNPKY-DAIRINQLYEQAKWAILLEEIECTEEEMMMFAALQYHINK 326
Cdd:pfam00373   1 DLELLLqDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEF 47
FERM_F1_TLN2 cd17174
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Talin-2 (TLN2); ...
 245-276 3.08e-03

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: 38.09  E-value: 3.08e-03
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 578825430 245 KAKINQ----GWLDSSRSLMEQDVKENEALLLRFKY 276
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); ...
 252-276 4.46e-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: 37.39  E-value: 4.46e-03
                         10        20
                 ....*....|....*....|....*
gi 578825430 252 WLDSSRSLMEQDVKENEALLLRFKY 276
Cdd:cd17173   88 WLDHGRTLREQGVEEHETLLLRRKF 112
PH2_AFAP cd13307
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; There are ...
 392-431 9.23e-03

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; There are 3 members of the AFAP family of adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. AFAP1 is a cSrc binding partner and actin cross-linking protein. AFAP1L1 is thought to play a similar role to AFAP1 in terms of being an actin cross-linking protein, but it preferentially binds to cortactin and not cSrc, thereby playing a role in invadosome formation. AFAP1L2 is a cSrc binding protein, but does not bind to actin filaments. AFAP1L2 acts as an intermediary between the RET/PTC kinase and PI-3kinase pathway in the thyroid. The AFAPs share a similar structure of a SH3 binding motif, 3 SH2 binding motifs, 2 PH domains, a coiled-coil region corresponding to the AFAP1 leucine zipper, and an actin binding domain. This cd is the second PH domain of AFAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270117  Cd Length: 101  Bit Score: 36.20  E-value: 9.23e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 578825430 392 YKQYWCTFKDTSISCYKSKEESSgTPAHQMNLRGCEVTPD 431
Cdd:cd13307   16 WRSRWCCVKDGQLHFYQDRNKTK-SPQQSLPLHGCEVVPG 54
 
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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