Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350276216     7 ETKGQFLIDHICNYYSLLEKDYFGIRYVDP-EKQRHWLEPNKSIFKQMKTHPPYTMCFRVKFYPHEPLKIKEELTRY-LL 84
Cdd:smart00295  19 STTAEELLETVCRKLGIRESEYFGLQFEDPdEDLRHWLDPAKTLLDQDVKSEPLTLYFRVKFYPPDPNQLKEDPTRLnLL 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350276216    85 YLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDYDPDEHP-ENYISEFEIFPKQ------SQKLERKIVEIHKNeLRGQ 157
Cdd:smart00295  99 YLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDlRGELSLKRFLPKQlldsrkLKEWRERIVELHKE-LIGL 177

                          170       180
                   ....*....|....*....|....
gi 350276216   158 SPPVAEFNLLLKAHTLETYGVDPH 181
Cdd:smart00295 178 SPEEAKLKYLELARKLPTYGVELF 201

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350276216     7 ETKGQFLIDHICNYYSLLEKDYFGIRYVDP-EKQRHWLEPNKSIFKQMKTHPPYTMCFRVKFYPHEPLKIKEELTRY-LL 84
Cdd:smart00295  19 STTAEELLETVCRKLGIRESEYFGLQFEDPdEDLRHWLDPAKTLLDQDVKSEPLTLYFRVKFYPPDPNQLKEDPTRLnLL 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350276216    85 YLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDYDPDEHP-ENYISEFEIFPKQ------SQKLERKIVEIHKNeLRGQ 157
Cdd:smart00295  99 YLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDlRGELSLKRFLPKQlldsrkLKEWRERIVELHKE-LIGL 177

                          170       180
                   ....*....|....*....|....
gi 350276216   158 SPPVAEFNLLLKAHTLETYGVDPH 181
Cdd:smart00295 178 SPEEAKLKYLELARKLPTYGVELF 201

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350276216   72 PLKIKEELTRYLLYLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDYDPDEHPENYISEFEIFPKQSQK------LERK 145
Cdd:pfam00373   3 ELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRkmkskeLEKR 82

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 350276216  146 IVEIHKNeLRGQSPPVAEFNLLLKAHTLETYGVDPH 181
Cdd:pfam00373  83 VLEAHKN-LRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

FERM adjacent (FA); This region is found adjacent to Band 4.1 / FERM domains (pfam00373) in a subset of FERM containing protein. The region has been hypothesized to play a role in regulatory adaptation, based on similarity to other protein kinase substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 350276216  279 KIFFKGSRFRYSGKVAKEVVEASSKIQREPPEVHRANITQSRSS 322
Cdd:pfam08736   1 KFFSLGSKFRYSGRTQKQTVEDSSEILRPQPEFERSPSKRYPSR 44

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350276216     7 ETKGQFLIDHICNYYSLLEKDYFGIRYVDP-EKQRHWLEPNKSIFKQMKTHPPYTMCFRVKFYPHEPLKIKEELTRY-LL 84
Cdd:smart00295  19 STTAEELLETVCRKLGIRESEYFGLQFEDPdEDLRHWLDPAKTLLDQDVKSEPLTLYFRVKFYPPDPNQLKEDPTRLnLL 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350276216    85 YLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDYDPDEHP-ENYISEFEIFPKQ------SQKLERKIVEIHKNeLRGQ 157
Cdd:smart00295  99 YLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDlRGELSLKRFLPKQlldsrkLKEWRERIVELHKE-LIGL 177

                          170       180
                   ....*....|....*....|....
gi 350276216   158 SPPVAEFNLLLKAHTLETYGVDPH 181
Cdd:smart00295 178 SPEEAKLKYLELARKLPTYGVELF 201

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 350276216   72 PLKIKEELTRYLLYLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDYDPDEHPENYISEFEIFPKQSQK------LERK 145
Cdd:pfam00373   3 ELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRkmkskeLEKR 82

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 350276216  146 IVEIHKNeLRGQSPPVAEFNLLLKAHTLETYGVDPH 181
Cdd:pfam00373  83 VLEAHKN-LRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 350276216   5 KRETKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKTHPPYTMCFRVKF 67
Cdd:cd01765   18 SKKATGQELFDKVCEKLNLLEKDYFGLFYEDNDGQKHWLDLDKKISKQLKRSGPYQFYFRVKF 80

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band 4.1-like protein 4A (EPB41L4A) and similar proteins; EPB41L4A, also termed protein NBL4, is a member of the band 4.1/Nbl4 (novel band 4.1-like protein 4) group of the FERM protein superfamily. It contains a FERM domain that 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). EPB41L4A is an important component of the beta-catenin/Tcf pathway. It may be related to determination of cell polarity or proliferation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 350276216   2 QLSKRETKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKTH-PPYTMCFRVKFY 68
Cdd:cd17107   21 QDGIKSSKGSVVLDVVFQHLNLLETDYFGLRYIDRQHQTHWLDPAKTLSEQLKLIgPPYTLYFGVKFY 88

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 1 (EPB41L1) and similar proteins; EPB41L1, also termed neuronal protein 4.1 (4.1N), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. It is a cytoskeleton-associated protein that may serve as a tumor suppressor in solid tumors. It suppresses hypoxia-induced epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) cells. The down-regulation of EPB41L1 expression is a critical step for non-small cell lung cancer (NSCLC) development. Moreover, EPB41L1 functions as a linker protein between inositol 1,4,5-trisphosphate receptor type1 (IP3R1) and actin filaments in neurons. EPB41L1 contains a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The 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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 350276216   5 KRETKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKThPPYTMCFRVKFYP 69
Cdd:cd17201   19 EKHARGQVLFDTVCEHLNLLEKDYFGLTFCDTESQKNWLDPSKEIKKQIRS-GPWHFAFTVKFYP 82

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like proteins; The family includes erythrocyte membrane protein band 4.1-like proteins EPB41L1/4.1N, EPB41L2/4.1G, and EPB41L3/4.1B. They belong to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L1 is a cytoskeleton-associated protein that may serve as a tumor suppressor in solid tumors. EPB41L2 is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L3 also acts as a tumor suppressor implicated in a variety of meningiomas and carcinomas. Members in this family contain a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal domain. The 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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 350276216   6 RETKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKTHpPYTMCFRVKFYP 69
Cdd:cd17106   20 KRAKGQVLFDKVCEHLNLLEKDYFGLTYRDAQDQKNWLDPAKEIKKQIRSG-PWLFSFNVKFYP 82

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band 4.1-like protein 4B (EPB41L4B); EPB41L4B, also termed FERM-containing protein CG1, or expressed in high metastatic cells (Ehm2), or Lulu2, is a member of the band 4.1/Nbl4 (novel band 4.1-like protein 4) group of the FERM protein superfamily. It contains a FERM domain that 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). EPB41L4B is a positive regulator of keratinocyte adhesion and motility, suggesting a role in wound healing. It also promotes cancer metastasis in melanoma, prostate cancer and breast cancer.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 350276216   6 RETKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKTHPPYTMCFRVKFYPHE 71
Cdd:cd17204   19 KHAKGQDLFDQIVYHLDLVETDYFGLQFMDAAQVAHWLDHTKPIKKQIKIGPPYTLHFRIKYYSSE 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, RhoGEF and pleckstrin domain-containing protein 1 (FARP1) and similar proteins; This family includes the F1 sub-domain of FERM, RhoGEF and pleckstrin domain-containing proteins FARP1, FARP2, and FERM domain-containing protein 7 (FRMD7). FARP1, also termed chondrocyte-derived ezrin-like protein (CDEP), or pleckstrin homology (PH) domain-containing family C member 2 (PLEKHC2), is a neuronal activator of the RhoA GTPase. It promotes outgrowth of developing motor neuron dendrites. It also regulates excitatory synapse formation and morphology, as well as activates the GTPase Rac1 to promote F-actin assembly. FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FRMD7 plays an important role in neuronal development and is involved in the regulation of F-actin, neurofilament, and microtubule dynamics. All family members contain a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 350276216  10 GQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKTHPPYTMCFRVKFYPHEP 72
Cdd:cd17098   23 GEVLFDQVCKHLNLLESDYFGLEFTDPEGNKCWLDPEKPILRQVKRPKDVVFKFVVKFYTPDP 85

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 350276216    7 ETKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMK 54
Cdd:pfam09379  16 KATGQVLLDQVCNHLNLKEKDYFGLQFLDDNGEHRWLDLSKRLSKQAP 63

FERM domain C-lobe of Protein 4.1 family; The protein 4.1 family includes four well-defined members: erythroid protein 4.1 (4.1R), the best known and characterized member, 4.1G (general), 4.1N (neuronal), and 4.1 B (brain). The less well understood 4.1O/FRMD3 is not a true member of this family and is not included in this hierarchy. Besides three highly conserved domains, FERM, SAB (spectrin and actin binding domain) and CTD (C-terminal domain), the proteins from this family contain several unique domains: U1, U2 and U3. FERM domains like other members of the FERM domain superfamily have a cloverleaf architecture with three distinct lobes: (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 brain is a particularly rich source of protein 4.1 isoforms. The various 4.1R, 4.1G, 4.1N, and 4.1B mRNAs are all expressed in distinct patterns within the brain. It is likely that 4.1 proteins play important functional roles in the brain including motor coordination and spatial learning, postmitotic differentiation, and synaptic architecture and function. In addition they are found in nonerythroid, nonneuronal cells where they may play a general structural role in nuclear architecture and/or may interact with splicing factors. The FERM C domain is the third structural domain within the FERM domain. 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 350276216 176 YGVDPHPCKDSTGTTTFLGFTAAGFVVFQGNKRIHLIKWPDVCKLKFEGKTFYV---IGTQKEKKAMLAFHTSTPAACKH 252
Cdd:cd13184    1 YGVDLHPAKDSEGVDIMLGVCSSGLLVYRDRLRINRFAWPKVLKISYKRNNFYIkirPGEFEQYETTIGFKLPNHRAAKR 80

                         90
                 ....*....|...
gi 350276216 253 LWKCGVENQAFYK 265
Cdd:cd13184   81 LWKVCVEHHTFFR 93

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 4 (PTPN4); PTPN4, also termed protein-tyrosine phosphatase MEG1 (MEG) or PTPase-MEG1, belongs to the non-transmembrane FERM-containing protein-tyrosine phosphatase (PTP) subfamily characterized by a conserved N-terminal FERM domain, a PDZ domain, and a C-terminal PTP catalytic domain. The 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). PTPN4 protects cells against apoptosis. It associates with the mitogen-activated protein kinase p38gamma (also known as MAPK12) to form a PTPN4-p38gamma complex that promotes cellular signaling, preventing cell death induction. It also inhibits tyrosine phosphorylation and subsequent cytoplasm translocation of TRIF-related adaptor molecule (TRAM, also known as TICAM2), resulting in the disturbance of TRAM-TRIF interaction. Moreover, PTPN4 negatively regulates cell proliferation and motility through dephosphorylation of CrkI.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 350276216   6 RETKGQFLIDHICNYYSLLEKDYFGIRYVD-PEKQRHWLEPNKSIFKQMKTHPPYTMCFRVKFY 68
Cdd:cd17194   20 KHDQGQVLLDLVFKHLDLTERDYFGLQLADdSTDNPRWLDPNKPIRKQLKRGSPHNLNFRVKFF 83

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins; The ezrin-radixin-moesin (ERM) family includes a group of closely related cytoskeletal proteins that play an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. They exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The 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). Merlin, which is highly related to the members of the ezrin, radixin, and moesin (ERM) protein family that are directly attached to and functionally linked with NHE1, is included in this family.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 350276216   8 TKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKTHP-PYTMCFRVKFYP 69
Cdd:cd17097   20 AKGRELFDLVCRTIGLRETWYFGLQYENKKGRVAWLKPDKKVLTQDVSKNnTLKFFFLVKFYP 82

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in E3 ubiquitin-protein ligase MYLIP and similar proteins; MYLIP, also termed inducible degrader of the LDL-receptor (Idol), or myosin regulatory light chain interacting protein (MIR), is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Its activity depends on E2 ubiquitin-conjugating enzymes of the UBE2D family, including UBE2D1, UBE2D2, UBE2D3, and UBE2D4. MYLIP stimulates clathrin-independent endocytosis and acts as a sterol-dependent inhibitor of cellular cholesterol uptake by binding directly to the cytoplasmic tail of the LDLR and promoting its ubiquitination via the UBE2D1/E1 complex. The ubiquitinated LDLR then enters the multivesicular body (MVB) protein-sorting pathway and is shuttled to the lysosome for degradation. Moreover, MYLIP has been identified as a novel ERM-like protein that affects cytoskeleton interactions regulating cell motility, such as neurite outgrowth. The ERM proteins includes ezrin, radixin, and moesin, which are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. MYLIP contains a FERM-domain and a C-terminal C3HC4-type RING-HC finger. The 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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 350276216   9 KGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKTHPPYTMCFRVKFY 68
Cdd:cd17104   22 NGQECLDKVCQKLGIIEKDYFGLQYTGPKGERLWLNLRNRISRQLPGPPPYRLRLRVKFF 81

FERM domain C-lobe of FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FRMD7(FERM domain containing 7). FARP1 and FARP2 are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. These members are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. Other members in this family do not contain the DH domains such as the Human FERM domain containing protein 7 and Caenorhabditis elegans CFRM3, both of which have unknown functions. They contain an N-terminal FERM domain, a PH domain, followed by a FA (FERM adjacent) domain. 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 350276216 170 AHTLETYGVDPHPCKDSTGTTTFLGFTAAGFVVFQGNKRIHLIKWPDVCKLKFEGKTFYV---IGTQKEKKAMLAFHTST 246
Cdd:cd13193    3 ARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFLIklhPEAYGSYKDTVEFSFES 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 350276216 247 PAACKHLWKCGVENQAFYKyaKSSQIKTVSSSKIFF-KGSRF 287
Cdd:cd13193   83 RNECKSFWKKCIEHHAFFR--CSEVPKPPSPKLRLFsRGSSF 122

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptors PTPN14, PTPN21, and similar proteins; This family includes tyrosine-protein phosphatase non-receptors PTPN14 and PTPN21, both of which are protein-tyrosine phosphatase (PTP). They belong to the FERM family of PTPs characterized by a conserved N-terminal FERM domain and a C-terminal PTP catalytic domain with an intervening sequence containing an acidic region and a putative SH3 domain-binding sequence. The 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). PTPN14 plays a role in the nucleus during cell proliferation. PTPN21 interacts with a Tec tyrosine kinase family member, the epithelial and endothelial tyrosine kinase (Etk, also known as Bmx), modulates Stat3 activation, and plays a role in the regulation of cell growth and differentiation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 350276216   7 ETKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQM-KTHPPYTMCFRVKFY 68
Cdd:cd17099   23 ESTGQDCLEYVAQRLELREIEYFGLRYVNKKGQLRWVDLEKPLKKQLdKHAHEPLLYFGVMFY 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF and pleckstrin domain-containing protein 2 (FARP2) and similar proteins; FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FARP2 contains a FERM domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains. The 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).

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gi 350276216   7 ETKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKThpPYTMCFR--VKFYPHEP 72
Cdd:cd17190   20 KADGQALLSQVFKRLNLVESDYFGLEFQNSQSNWIWLEPMKLIVKQVRR--PKNTKLRlaVKFFPPDP 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 7 (FRMD7); FRMD7 plays an important role in neuronal development and is involved in the regulation of F-actin, neurofilament, and microtubule dynamics. It interacts with the Rho GTPase regulator, RhoGDIalpha, and activates the Rho subfamily member Rac1, which regulates reorganization of actin filaments and controls neuronal outgrowth. Mutations in the FRMD7 gene are responsible for the X-linked idiopathic congenital nystagmus (ICN), a disease which affects ocular motor control. FRMD7 contains a FERM domain, and a pleckstrin homology (PH) domain. The 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).

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gi 350276216  10 GQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQMKTHPPYTMCFRVKFYPHEP 72
Cdd:cd17188   24 GKDLFNMSCSHLNLVEKEYFGLEFRNHAGNNVWLELLKPITKQIKNPKELIFKFTVKFFPVDP 86

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in merlin and similar proteins; Merlin, also termed moesin-ezrin-radixin-like protein, or neurofibromin-2 (NF2), or Schwannomerlin, or Schwannomin, is a member of the ezrin/radixin/moesin (ERM) family of cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif, merlin however lacks the typical actin-binding motif in the C-tail. The 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). Merlin plays vital roles in controlling proper development of organ sizes by specifically binding to a large number of target proteins localized both in cytoplasm and nuclei. Merlin may function as a tumor suppressor that functions upstream of the core Hippo pathway kinases Lats1/2 (Wts in Drosophila) and Mst1/2 (Hpo in Drosophila), as well as the nuclear E3 ubiquitin ligase DDB1-and-Cullin 4-associated Factor 1 (DCAF1)-associated cullin 4-Roc1 ligase, CRL4(DCAF1). Merlin may also has a tumor suppressor function in melanoma cells, the inhibition of the proto-oncogenic Na(+)/H(+) exchanger isoform 1 (NHE1) activity.

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gi 350276216   8 TKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQ-MKTHPPYTMCFRVKFYP 69
Cdd:cd17186   22 WKGKDLFDLVCRTIGLRETWYFGLQYTDSKGTVAWLKMDKKVLDQdVPKEEPVTFHFLAKFYP 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing proteins FRMD4A, FRMD4B, and similar proteins; This family includes FERM domain-containing proteins FRMD4A and FRMD4B, both of which contain a FERM domain that 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). FRMD4A is a cytohesin adaptor involved in cell structure, transport and signaling. It promotes the growth of cancer cells in tongue, head and neck squamous cell carcinomas. FRMD4B, also termed GRP1-binding protein GRSP1, interacts with the coil-coil domain of ARF exchange factor GRP1 to form the Grsp1-Grp1 complex that co-localizes with cortical actin rich regions in response to stimulation of CHO-T cells with insulin or epidermal growth factor (EGF).

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gi 350276216  13 LIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSI----FKQMKTHPPYTMCFRVKFY 68
Cdd:cd17103   28 LLDLVASHFNLKEKEYFGLAYEDETGHYNWLQLDKRVldheFPKKWSSGPLVLHFAVKFY 87

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in moesin and similar proteins; Moesin, also termed membrane-organizing extension spike protein, is a member of the ezrin/radixin/moesin (ERM) family of cytoskeletal proteins that plays an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. The C-terminal domain can fold back to bind to the FERM domain forming an autoinhibited conformation. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Moesin is involved in mitotic spindle function through stabilizing cell shape and microtubules at the cell cortex. It is required for the formation of F-actin networks that mediate endosome biogenesis or maturation and transport through the degradative pathway.

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gi 350276216   8 TKGQFLIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQ-MKTHPPYTMCFRVKFYP 69
Cdd:cd17237   21 TTGKQLFDQVVKTIGLREVWFFGLQYQDTKGFSTWLKLNKKVTAQdVRKESPLLFKFRAKFYP 83

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 4A (FRMD4A); FRMD4A is a cytohesin adaptor involved in cell structure, transport and signaling. It promotes the growth of cancer cells in tongue, head and neck squamous cell carcinomas. It also regulates tau secretion by activating cytohesin-Arf6 signaling through connecting cytohesin family Arf6-specific guanine-nucleotide exchange factors (GEFs) and Par-3 at primordial adherens junctions during epithelial polarization. As a genetic risk factor for late-onset Alzheimer's disease (AD), FRMD4A may play a role in amyloidogenic and tau-related pathways in AD. FRMD4A contains a FERM domain that 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).

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gi 350276216  13 LIDHICNYYSLLEKDYFGIRYVDPEKQRHWLEPNKSIFKQ--MKTHPPYTMCFRVKFY 68
Cdd:cd17199   28 LLDLVASHFNLKEKEYFGIAFTDETGHLNWLQLDRRVLEHdfPKKSGPVVLYFCVRFY 85