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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   88 RPQKIRMLDGSVKTVMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLRDERKMEKLKAKL 167
Cdd:cd17174     1 RPQKIRMLDGAVKTIMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLRDERKMEKLKAKL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 156938343  168 HTDDDLNWLDHSRTFREQGVDENETLLLRRKF 199
Cdd:cd17174    81 HTDDDLNWLDHSRTFREQGVDENETLLLRRKF 112

Talin, middle domain; Members of this family adopt a structure consisting of five alpha helices that fold into a bundle. They contain a Vinculin binding site (VBS) composed of a hydrophobic surface spanning five turns of helix four. Activation of the VBS causes subsequent recruitment of Vinculin, which enables maturation of small integrin/talin complexes into more stable adhesions. Formation of the complex between VBS and Vinculin requires prior unfolding of this middle domain: once released from the talin hydrophobic core, the VBS helix is then available to induce the 'bundle conversion' conformational change within the vinculin head domain thereby displacing the intramolecular interaction with the vinculin tail, allowing vinculin to bind actin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   494 AQQALMGTINTSMHAVQQAQDDLSELDSLPPLGQDMASRVWVQNKVDESKHEIHSQVDAITAGTASVVNLTAGDPADTDY 573
Cdd:pfam09141    1 PQRALLGTISAGQEAIQAAEAELDTPAQLPPLGSDAASLQWRENTLDVSKQNVSSQLAAMNAATAQVVTLTSGPPDEIDY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   574 TAVGCAITTISSNLTEMSKGVKLLAALMDDEvGSGEDLLRAARTLAGAVSDLLKAVQPTSGEPRQTVLTAAGSIGQASGD 653
Cdd:pfam09141   81 TAVGAAITTISSNLPEMSKGVRMLAALMDDE-DSGDKLLDAARKLCGAFSDLLKAAQPESKEPRQNLLNAASRVGEASQQ 159

                   ..
gi 156938343   654 LL 655
Cdd:pfam09141  160 LL 161

FERM domain C-lobe/F3 of Talin; Talin (also called filopodin) plays an important role in initiating actin filament growth in motile cell protrusions. It is responsible for linking the cytoplasmic domains of integrins to the actin-based cytoskeleton, and is involved in vinculin, integrin and actin interactions. At the leading edge of motile cells, talin colocalises with the hyaluronan receptor layilin in transient adhesions, some of which become more stable focal adhesions (FA). During this maturation process, layilin is replaced with integrins, where localized production of PI(4,5)P(2) by type 1 phosphatidyl inositol phosphate kinase type 1gamma (PIPK1gamma) is thought to play a role in FA assembly. Talins are composed of a N-terminal region FERM domain which us made up of 3 subdomains (N, alpha-, and C-lobe; or- A-lobe, B-lobe, and C-lobe; or F1, F2, and F3) connected by short linkers, a talin rod which binds vinculin, and a conserved C-terminal region with actin- and integrin-binding sites. There are 2 additional actin-binding domains, one in the talin rod and the other in the FERM domain. Both the F2 and F3 FERM subdomains contribute to F-actin binding. Subdomain F3 of the FERM domain contains overlapping binding sites for integrin cytoplasmic domains and for the type 1 gamma isoform of PIP-kinase (phosphatidylinositol 4-phosphate 5-kinase). The FERM domain has a cloverleaf tripart structure . F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343  312 GVSFFLVKEKMKGKNKLVPRLLGITKDSVMRVDEKTKEVLQEWPLTTVKRWAASPKSFTLDFGEYQESYYSVQTTEGEQI 391
Cdd:cd10569     1 GVTFFLVKEKMKGKNKLVPRLLGITKESVLRLDEETKEVLKVWPLTTIKRWAASPKSFTLDFGDYSENYYSVQTTEGEQI 80

                          90
                  ....*....|..
gi 156938343  392 SQLIAGYIDIIL 403
Cdd:cd10569    81 SQLISGYIDIIL 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   203 DQNVDSRDPVQLNLLYVQARDDILNGSHPVSFEKACEFGGFQAQIQFGPHVEHKHKPGFLDLKEFLPKEYIKQRGA---E 279
Cdd:pfam00373    1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRKMKSkelE 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 156938343   280 KRIFQEHKNCGEMSEIEAKVKYVKLARSLRTYGVSFF 316
Cdd:pfam00373   81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

I/LWEQ domain; I/LWEQ domains bind to actin. It has been shown that the I/LWEQ domains from mouse talin and yeast Sla2p interact with F-actin. I/LWEQ domains can be placed into four major groups based on sequence similarity: (1) Metazoan talin; (2) Dictyostelium TalA/TalB and SLA110; (3) metazoan Hip1p; and (4) yeast Sla2p. The domain has four conserved blocks, the name of the domain is derived from the initial conserved amino acid of each of the four blocks.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   689 AKNVA------QVAEDTVLQN-----RVIAAATQCALSTSQLVACAKVVSPTISSpvCQEQLIEAGKLVDRSVENCVRAC 757
Cdd:pfam01608   13 AKAVAaatnllVEAADGVVQGqgseeELIVAAKEVAASTAQLVAASRVKADPNSK--TQQRLEAASKAVTDATKNLVAAV 90

                   ....*...
gi 156938343   758 QAATTDSE 765
Cdd:pfam01608   91 KSAAELQE 98

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   88 RPQKIRMLDGSVKTVMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLRDERKMEKLKAKL 167
Cdd:cd17174     1 RPQKIRMLDGAVKTIMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLRDERKMEKLKAKL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 156938343  168 HTDDDLNWLDHSRTFREQGVDENETLLLRRKF 199
Cdd:cd17174    81 HTDDDLNWLDHSRTFREQGVDENETLLLRRKF 112

Talin, middle domain; Members of this family adopt a structure consisting of five alpha helices that fold into a bundle. They contain a Vinculin binding site (VBS) composed of a hydrophobic surface spanning five turns of helix four. Activation of the VBS causes subsequent recruitment of Vinculin, which enables maturation of small integrin/talin complexes into more stable adhesions. Formation of the complex between VBS and Vinculin requires prior unfolding of this middle domain: once released from the talin hydrophobic core, the VBS helix is then available to induce the 'bundle conversion' conformational change within the vinculin head domain thereby displacing the intramolecular interaction with the vinculin tail, allowing vinculin to bind actin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   494 AQQALMGTINTSMHAVQQAQDDLSELDSLPPLGQDMASRVWVQNKVDESKHEIHSQVDAITAGTASVVNLTAGDPADTDY 573
Cdd:pfam09141    1 PQRALLGTISAGQEAIQAAEAELDTPAQLPPLGSDAASLQWRENTLDVSKQNVSSQLAAMNAATAQVVTLTSGPPDEIDY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   574 TAVGCAITTISSNLTEMSKGVKLLAALMDDEvGSGEDLLRAARTLAGAVSDLLKAVQPTSGEPRQTVLTAAGSIGQASGD 653
Cdd:pfam09141   81 TAVGAAITTISSNLPEMSKGVRMLAALMDDE-DSGDKLLDAARKLCGAFSDLLKAAQPESKEPRQNLLNAASRVGEASQQ 159

                   ..
gi 156938343   654 LL 655
Cdd:pfam09141  160 LL 161

FERM domain C-lobe/F3 of Talin; Talin (also called filopodin) plays an important role in initiating actin filament growth in motile cell protrusions. It is responsible for linking the cytoplasmic domains of integrins to the actin-based cytoskeleton, and is involved in vinculin, integrin and actin interactions. At the leading edge of motile cells, talin colocalises with the hyaluronan receptor layilin in transient adhesions, some of which become more stable focal adhesions (FA). During this maturation process, layilin is replaced with integrins, where localized production of PI(4,5)P(2) by type 1 phosphatidyl inositol phosphate kinase type 1gamma (PIPK1gamma) is thought to play a role in FA assembly. Talins are composed of a N-terminal region FERM domain which us made up of 3 subdomains (N, alpha-, and C-lobe; or- A-lobe, B-lobe, and C-lobe; or F1, F2, and F3) connected by short linkers, a talin rod which binds vinculin, and a conserved C-terminal region with actin- and integrin-binding sites. There are 2 additional actin-binding domains, one in the talin rod and the other in the FERM domain. Both the F2 and F3 FERM subdomains contribute to F-actin binding. Subdomain F3 of the FERM domain contains overlapping binding sites for integrin cytoplasmic domains and for the type 1 gamma isoform of PIP-kinase (phosphatidylinositol 4-phosphate 5-kinase). The FERM domain has a cloverleaf tripart structure . F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343  312 GVSFFLVKEKMKGKNKLVPRLLGITKDSVMRVDEKTKEVLQEWPLTTVKRWAASPKSFTLDFGEYQESYYSVQTTEGEQI 391
Cdd:cd10569     1 GVTFFLVKEKMKGKNKLVPRLLGITKESVLRLDEETKEVLKVWPLTTIKRWAASPKSFTLDFGDYSENYYSVQTTEGEQI 80

                          90
                  ....*....|..
gi 156938343  392 SQLIAGYIDIIL 403
Cdd:cd10569    81 SQLISGYIDIIL 92

I/LWEQ domain; I/LWEQ domains bind to actin. It has been shown that the I/LWEQ domains from mouse talin and yeast Sla2p interact with F-actin. I/LWEQ domains can be placed into four major groups based on sequence similarity: (1) Metazoan talin; (2) Dictyostelium TalA/TalB and SLA110; (3) metazoan Hip1p; and (4) yeast Sla2p. The domain has four conserved blocks, the name of the domain is derived from the initial conserved amino acid of each of the four blocks.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343  2386 DDGQWSQGLISAARMVAAATSSLCEAANASVQGHASEEKLISSAKQVAASTAQLLVACKVKADQDSEAMRRLQAAGNAVK 2465
Cdd:pfam01608    1 KNNRWTEGLISAAKAVAAATNLLVEAADGVVQGQGSEEELIVAAKEVAASTAQLVAASRVKADPNSKTQQRLEAASKAVT 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 156938343  2466 RASDNLVRAAQKAAFGKADDDDVVV---KTKFVGGIAQIIAAQEEMLKKERELEEARKKLAQIRQQQYK 2531
Cdd:pfam01608   81 DATKNLVAAVKSAAELQEEEIEEEMdfsKLSLHQAKRQEMEAQVEILKLEKELEEARKKLAEIRKAHYH 149

N-terminal or F0 domain of Talin-head FERM; FERM_f0 forms a stable globular structure. The fold is an ubiquitin-like fold joined to the f1 domain in a novel fixed orientation by an extensive charged interface. It is required for maximal integrin-activation, by interacting with other FA components, No binding partner has yet been found for it.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343     4 LSLKICVRHCNVVKTMQFEPSTAVYDACRVIRERVPEAQtGQASDYGLFLSDEDPRKGIWLEAGRTLDYYMLRNGDILEY 83
Cdd:pfam16511    1 LSLKISIVGSNVTKTMQFDPSTTVYDACRLIREKIPEGG-LNASEYGLFLADEDPKKGRWLEPGRTLEYYDLRNGDELEY 79

                   ..
gi 156938343    84 KK 85
Cdd:pfam16511   80 KK 81

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343  213 QLNLLYVQARDDILNGSHPVSFEKACEFGGFQAQIQFGPHVEHKHKPGFLDLKEFLPKEYIKQRGA---EKRIFQEHKNC 289
Cdd:cd14473     1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKPeewEKRIVELHKKL 80

                          90
                  ....*....|....*....
gi 156938343  290 GEMSEIEAKVKYVKLARSL 308
Cdd:cd14473    81 RGLSPAEAKLKYLKIARKL 99

FERM N-terminal domain; This domain is the N-terminal ubiquitin-like structural domain of the FERM domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343    92 IRMLDGSVKTVMVDDSKTVGELLVTICSRIGITNYEEYSLiqETIEEKKEEgtgtlkkdrtllrderkmeklkaklhtdd 171
Cdd:pfam09379    1 VRLLDGTVLEFDVQPKATGQVLLDQVCNHLNLKEKDYFGL--QFLDDNGEH----------------------------- 49

                           90
                   ....*....|....*.
gi 156938343   172 dlNWLDHSRTFREQGV 187
Cdd:pfam09379   50 --RWLDLSKRLSKQAP 63

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   88 RPQKIRMLDGSVKTVMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLRDERKMEKLKAKL 167
Cdd:cd17174     1 RPQKIRMLDGAVKTIMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLRDERKMEKLKAKL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 156938343  168 HTDDDLNWLDHSRTFREQGVDENETLLLRRKF 199
Cdd:cd17174    81 HTDDDLNWLDHSRTFREQGVDENETLLLRRKF 112

Talin, middle domain; Members of this family adopt a structure consisting of five alpha helices that fold into a bundle. They contain a Vinculin binding site (VBS) composed of a hydrophobic surface spanning five turns of helix four. Activation of the VBS causes subsequent recruitment of Vinculin, which enables maturation of small integrin/talin complexes into more stable adhesions. Formation of the complex between VBS and Vinculin requires prior unfolding of this middle domain: once released from the talin hydrophobic core, the VBS helix is then available to induce the 'bundle conversion' conformational change within the vinculin head domain thereby displacing the intramolecular interaction with the vinculin tail, allowing vinculin to bind actin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   494 AQQALMGTINTSMHAVQQAQDDLSELDSLPPLGQDMASRVWVQNKVDESKHEIHSQVDAITAGTASVVNLTAGDPADTDY 573
Cdd:pfam09141    1 PQRALLGTISAGQEAIQAAEAELDTPAQLPPLGSDAASLQWRENTLDVSKQNVSSQLAAMNAATAQVVTLTSGPPDEIDY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   574 TAVGCAITTISSNLTEMSKGVKLLAALMDDEvGSGEDLLRAARTLAGAVSDLLKAVQPTSGEPRQTVLTAAGSIGQASGD 653
Cdd:pfam09141   81 TAVGAAITTISSNLPEMSKGVRMLAALMDDE-DSGDKLLDAARKLCGAFSDLLKAAQPESKEPRQNLLNAASRVGEASQQ 159

                   ..
gi 156938343   654 LL 655
Cdd:pfam09141  160 LL 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   88 RPQKIRMLDGSVKTVMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLRDERKMEKLKAKL 167
Cdd:cd17173     1 RPLKIRMLDGTVKTVMVDDSKTVTDMLMTICARIGITNHDEYSLVREIMEEKKEEVTGTLKKDKTLLRDDKKMEKLKQKL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 156938343  168 HTDDDLNWLDHSRTFREQGVDENETLLLRRKF 199
Cdd:cd17173    81 HTDDELNWLDHGRTLREQGVEEHETLLLRRKF 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   88 RPQKIRMLDGSVKTVMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTgTLKKDRTLLRDERKMEKLKAKL 167
Cdd:cd17090     1 RPLRVRTLDGSVKTVLVDDSQTVSQLVETICTKIGITNPEEFSLVREEEEEEKENKA-TLRKSTSRLRDDKKMESLKKKL 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 156938343  168 HTDDDLNWLDHSRTFREQGVDENETLLLRRKF 199
Cdd:cd17090    80 HTDDELNWLDHDQTLREQGVDEDETLLLRRKF 111

I/LWEQ domain; I/LWEQ domains bind to actin. It has been shown that the I/LWEQ domains from mouse talin and yeast Sla2p interact with F-actin. I/LWEQ domains can be placed into four major groups based on sequence similarity: (1) Metazoan talin; (2) Dictyostelium TalA/TalB and SLA110; (3) metazoan Hip1p; and (4) yeast Sla2p. The domain has four conserved blocks, the name of the domain is derived from the initial conserved amino acid of each of the four blocks.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343  2386 DDGQWSQGLISAARMVAAATSSLCEAANASVQGHASEEKLISSAKQVAASTAQLLVACKVKADQDSEAMRRLQAAGNAVK 2465
Cdd:pfam01608    1 KNNRWTEGLISAAKAVAAATNLLVEAADGVVQGQGSEEELIVAAKEVAASTAQLVAASRVKADPNSKTQQRLEAASKAVT 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 156938343  2466 RASDNLVRAAQKAAFGKADDDDVVV---KTKFVGGIAQIIAAQEEMLKKERELEEARKKLAQIRQQQYK 2531
Cdd:pfam01608   81 DATKNLVAAVKSAAELQEEEIEEEMdfsKLSLHQAKRQEMEAQVEILKLEKELEEARKKLAEIRKAHYH 149

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343    2 VALSLKICVRhcNVVKTMQFEPSTAVYDACRVIRERVPEAQTGQASDYGLFLSDEDPRKGIWLEAGRTLDYYMLRNGDIL 81
Cdd:cd17171     1 VALSLKISIG--NVVKTMQFEPSTMVYDACRMIRERVPEAQAGQPNDFGLFLSDDDPKKGIWLEAGKALDYYMLRNGDTM 78

                  ....*.
gi 156938343   82 EYKKKQ 87
Cdd:cd17171    79 EYRKKQ 84

N-terminal or F0 domain of Talin-head FERM; FERM_f0 forms a stable globular structure. The fold is an ubiquitin-like fold joined to the f1 domain in a novel fixed orientation by an extensive charged interface. It is required for maximal integrin-activation, by interacting with other FA components, No binding partner has yet been found for it.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343     4 LSLKICVRHCNVVKTMQFEPSTAVYDACRVIRERVPEAQtGQASDYGLFLSDEDPRKGIWLEAGRTLDYYMLRNGDILEY 83
Cdd:pfam16511    1 LSLKISIVGSNVTKTMQFDPSTTVYDACRLIREKIPEGG-LNASEYGLFLADEDPKKGRWLEPGRTLEYYDLRNGDELEY 79

                   ..
gi 156938343    84 KK 85
Cdd:pfam16511   80 KK 81

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343  213 QLNLLYVQARDDILNGSHPVSFEKACEFGGFQAQIQFGPHVEHKHKPGFLDLKEFLPKEYIKQRGA---EKRIFQEHKNC 289
Cdd:cd14473     1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKPeewEKRIVELHKKL 80

                          90
                  ....*....|....*....
gi 156938343  290 GEMSEIEAKVKYVKLARSL 308
Cdd:cd14473    81 RGLSPAEAKLKYLKIARKL 99

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343   88 RPQKIRMLDGSVKTVMVDDSKTVGELLVTICSRIGITNYEEYSLIQETieekkeegtgtLKKDRTLLRderkmeklKAKL 167
Cdd:cd17096     1 KTLRIQLPDLQYLDLRVDFSVKVFNAVVDLCKELGIRHPEELSLLRPP-----------LYRPKSLVD--------KARL 61

                          90       100       110
                  ....*....|....*....|....*....|...
gi 156938343  168 HTdddlNWLDHSRTFREQGVDENETLLLRRKFF 200
Cdd:cd17096    62 NS----GWLDSSRSLMEQGVRENDTLLLRFKYY 90

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343  102 VMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLrDERKMEKlkaklhtdddlNWLDHSRT 181
Cdd:cd17184    15 VKVNFSDRVFKAVSDICKTFNIRHPEELSLLRKPRDPTKKKKLAKMYKPQSLL-DKAKINQ-----------GWLDSSRS 82

                          90
                  ....*....|....*....
gi 156938343  182 FREQGVDENETLLLRRKFF 200
Cdd:cd17184    83 LMEQDVKENEALLLRFKYY 101

rod-segment of the talin C-terminal domain; The talin rod-segment characterize by this model interacts with its N-terminal FERM domain to mask its integrin-binding site and interferes with interactions between the FERM domain and the cellular membrane. Talin is a large and ubiquitous cytoskeletal protein concentrated at focal adhesion sites. It is involved in linking integrins to the actin cytoskeleton.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343 1045 EACGPMEIDSALNTVQTLKNELQDAKMAAVESQLKPLPGETLEKCAQDLGSTSKAVGSSMAQlLTCAAQGNEHYTGVAAR 1124
Cdd:cd12150     1 KAPGQRECDQAIETLNNCIRELDQASLAAISQGLAPRRDNSLQGFQEQMLHSVSEILDKIEP-LRSAAKGEAEQLGHAVT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 156938343 1125 ETAQALKTLAQAARGVAASTTDPAAAHAMLDSARDVMEGSAMLIQEAKQA 1174
Cdd:cd12150    80 QMAQYFEPLVQAAIGAASKTVNSQQQMALLDQTKTVAESALQLVYAAKEA 129

FERM domain C-lobe of the Fermitin family; Fermitin functions as a mediator of integrin inside-out signalling. The recruitment of Fermitin proteins and Talin to the membrane mediates the terminal event of integrin signalling, via interaction with integrin beta subunits. Fermatin has FERM domain interrupted with a pleckstrin homology (PH) domain. Fermitin family homologs (Fermt1, 2, and 3, also known as Kindlins) are each encoded by a different gene. In mammalian studies, Fermt1 is generally expressed in epithelial cells, Fermt2 is expressed inmuscle tissues, and Fermt3 is expressed in hematopoietic lineages. Specifically Fermt2 is expressed in smooth and striated muscle tissues in mice and in the somites (a trunk muscle precursor) and neural crest in Xenopus embryos. As such it has been proposed that Fermt2 plays a role in cardiomyocyte and neural crest differentiation. Expression of mammalian Fermt3 is associated with hematopoietic lineages: the anterior ventral blood islands, vitelline veins, and early myeloid cells. In Xenopus embryos this expression, also include the notochord and cement gland. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). This cd is not included in the C-lobe hierarchy based on its position in the tree. One thing to note is that unlike the other members of the C-lobe hierarchy it contains 2 FERM M domains which might also reflect a difference in its evolutionary history. The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343  311 YGVSFFLVKEKMKGKNKLvprlLGITKDSVMRVDEKTKEVLQEWPLTTVKRWAAS--PKSFTLDFGEYQESyYSVQTTEG 388
Cdd:cd13205     2 FGITYFIVRFRGSKKEEL----LGVAYNRLIRMDLHTGDPIKTWRYSTMKAWNVNweIREVIIQFEDENIA-FACLSADC 76

                          90
                  ....*....|.
gi 156938343  389 EQISQLIAGYI 399
Cdd:cd13205    77 KIVHEFIGGYI 87

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Dictyostelium discoideum Myosin-VIIa (DdMyo7) and similar proteins; DdMyo7, also termed Myosin-I heavy chain, or class VII unconventional myosin, or M7, plays a role in adhesion in Dictyostelium where it is a component of a complex of proteins that serve to link membrane receptors to the underlying actin cytoskeleton. It interacts with talinA, an actin-binding protein with a known role in cell-substrate adhesion. DdMyo7 is required for phagocytosis. It is also essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin. Members in this family contain a myosin motor domain, two MyTH4 domains, two FERM (Band 4.1, ezrin, radixin, moesin) domains, and two Pleckstrin homology (PH) domains. Some family members contain an extra SH3 domain. Each FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 156938343   91 KIRMLDGSVKTVMVDDSKTVGELLVTICSRIGITNYEE-YSLIQ 133
Cdd:cd17208     7 RFYFLDGQFKALEFDSAATAAEVLEQLKQKIGLRSTADgFALYE 50

FERM domain C-lobe, repeat 2, of Myosin VII (MyoVII, Myo7); MyoVII, a MyTH-FERM myosin, is an actin-based motor protein essential for a variety of biological processes in the actin cytoskeleton function. Mutations in MyoVII leads to problems in sensory perception: deafness and blindness in humans (Usher Syndrome), retinal defects and deafness in mice (shaker 1), and aberrant auditory and vestibular function in zebrafish. Myosin VIIAs have plus (barbed) end-directed motor activity on actin filaments and a characteristic actin-activated ATPase activity. MyoVII consists of a conserved spectrin-like, SH3 subdomain N-terminal region, a motor/head region, a neck made of 4-5 IQ motifs, and a tail consisting of a coiled-coil domain, followed by a tandem repeat of myosin tail homology 4 (MyTH4) domains and partial FERM domains that are separated by an SH3 subdomain and are thought to mediate dimerization and binding to other proteins or cargo. Members include: MyoVIIa, MyoVIIb, and MyoVII members that do not have distinct myosin VIIA and myosin VIIB genes. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156938343  312 GVSFFLVKEKmkGKNKLVPRLL-GITKDSVMRVDEKTKEVLQEWPLTTVKRWAASPKSFTLDFGEY-QESYYSVQTTEGE 389
Cdd:cd13199     1 GSAFFEVKQT--TDPSLPEILLiAINKNGVSLIDPKTKEILATHPFSKISNWSSGNTYFHMTIGNLvRGSKLLCETSLGY 78

                          90
                  ....*....|....*...
gi 156938343  390 QISQLIAGYIDIILKKKQ 407
Cdd:cd13199    79 KMDDLLTSYISLLLSNMK 96