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 17505677     29 RCNVHLLhDSDIIGNEFPRTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHK-HRYWLDLTRSINHVVKnfKTESMTLHLR 107
Cdd:smart00295   1 VLKVYLL-DGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEdLRHWLDPAKTLLDQDV--KSEPLTLYFR 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677    108 FRYYPSDPARLRDPNLRY-QLFVQLQRDLLHGRLYCPTSSAAELAALILQAQLGDYNEEKH-VGNYVSGYKLLLKQT--- 182
Cdd:smart00295  78 VKFYPPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHdLRGELSLKRFLPKQLlds 157

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 17505677    183 ---PKLEERIANNHKELKGKSSESAELEFLEKASQLDTY 218
Cdd:smart00295 158 rklKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTY 196

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 17505677     29 RCNVHLLhDSDIIGNEFPRTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHK-HRYWLDLTRSINHVVKnfKTESMTLHLR 107
Cdd:smart00295   1 VLKVYLL-DGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEdLRHWLDPAKTLLDQDV--KSEPLTLYFR 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677    108 FRYYPSDPARLRDPNLRY-QLFVQLQRDLLHGRLYCPTSSAAELAALILQAQLGDYNEEKH-VGNYVSGYKLLLKQT--- 182
Cdd:smart00295  78 VKFYPPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHdLRGELSLKRFLPKQLlds 157

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 17505677    183 ---PKLEERIANNHKELKGKSSESAELEFLEKASQLDTY 218
Cdd:smart00295 158 rklKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTY 196

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 17505677 124 RYQLFVQLQRDLLHGRLYCPTSSAAELAALILQAQLGDYNEEKHVGNYVSGYKLLLKQT------PKLEERIANNHKELK 197
Cdd:cd14473   2 RYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLlkqrkpEEWEKRIVELHKKLR 81

                        90
                ....*....|....*...
gi 17505677 198 GKSSESAELEFLEKASQL 215
Cdd:cd14473  82 GLSPAEAKLKYLKIARKL 99

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 17505677     29 RCNVHLLhDSDIIGNEFPRTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHK-HRYWLDLTRSINHVVKnfKTESMTLHLR 107
Cdd:smart00295   1 VLKVYLL-DGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEdLRHWLDPAKTLLDQDV--KSEPLTLYFR 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677    108 FRYYPSDPARLRDPNLRY-QLFVQLQRDLLHGRLYCPTSSAAELAALILQAQLGDYNEEKH-VGNYVSGYKLLLKQT--- 182
Cdd:smart00295  78 VKFYPPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHdLRGELSLKRFLPKQLlds 157

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 17505677    183 ---PKLEERIANNHKELKGKSSESAELEFLEKASQLDTY 218
Cdd:smart00295 158 rklKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTY 196

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 17505677 124 RYQLFVQLQRDLLHGRLYCPTSSAAELAALILQAQLGDYNEEKHVGNYVSGYKLLLKQT------PKLEERIANNHKELK 197
Cdd:cd14473   2 RYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLlkqrkpEEWEKRIVELHKKLR 81

                        90
                ....*....|....*...
gi 17505677 198 GKSSESAELEFLEKASQL 215
Cdd:cd14473  82 GLSPAEAKLKYLKIARKL 99

FERM domain C-lobe of FERM domain-containing protein 3 and 5 (FRMD3 and 5); FRMD3 (also called Band 4.1-like protein 4O/4.1O though it is not a true member of that family) is a novel putative tumor suppressor gene that is implicated in the origin and progression of lung cancer. In humans there are 5 isoforms that are produced by alternative splicing. Less is known about FRMD5, though there are 2 isoforms of the human protein are produced by alternative splicing. Both FRMD3 and FRMD5 contain a N-terminal FERM domain, followed by a FERM adjacent (FA) domain, and 4.1 protein C-terminal domain (CTD). 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 17505677 204 AELEFLEKASQLDTYAFDPYTIKEPHDTlPVYIGASCKGILIYTGQSRTHNIDWSELVKVDYSGKEIRLTLSENyrgqit 283
Cdd:cd13192   1 AEDNFLRKAATLETYGVDPHPVKDHRGN-QLYLGFTHTGIVTFQGGKRVHHFRWNDITKFNYEGKMFILHVMQK------ 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 17505677 284 aagtptgtlnghgpgspsimdkslTKKPLTLKYTCPSGQFAKHLWIHILSQQAFF 338
Cdd:cd13192  74 ------------------------EEKKHTLGFKCPTPAACKHLWKCAVEQQAFY 104

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like 5 (EPB41L5); EPB41L5 is a mesenchymal-specific protein that is an integral component of the ARF6-based pathway. It is normally induced during epithelial-mesenchymal transition (EMT) by an EMT-related transcriptional factor, ZEB1, which drives ARF6-based invasion, metastasis and drug resistance. EPB41L5 also binds to paxillin to enhance integrin/paxillin association, and thus promotes focal adhesion dynamics. Moreover, EPB41L5 acts as a substrate for the E3 ubiquitin ligase Mind bomb 1 (Mib1), which is essential for activation of Notch signaling. EPB41L5 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).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677  28 VRCNVHLLHDSDIiGNEFPRTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHKHRYWLDLTRSINHVVKnfKTESMTLHLR 107
Cdd:cd17205   3 ITCRVSLLDGTDV-SVDLPKKAKGQELFEQIMYHLDLIEKDYFGLRFMDSAQVAHWLDVTKSIKKQVK--IGPPYCLHLR 79

                ....*..
gi 17505677 108 FRYYPSD 114
Cdd:cd17205  80 VKFYSSE 86

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677  26 KDVRCNVHLLHDSDIIGN---EFPRTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHKHRYWLDLTRSINHVVKnFKTESM 102
Cdd:cd17107   1 EEFYCEIVLLDESELILTiqqDGIKSSKGSVVLDVVFQHLNLLETDYFGLRYIDRQHQTHWLDPAKTLSEQLK-LIGPPY 79

                        90
                ....*....|..
gi 17505677 103 TLHLRFRYYPSD 114
Cdd:cd17107  80 TLYFGVKFYAED 91

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 3 (EPB41L3) and similar proteins; EPB41L3, also termed 4.1B, or differentially expressed in adenocarcinoma of the lung protein 1 (DAL-1), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L3 is a tumor suppressor that has been implicated in a variety of meningiomas and carcinomas. EPB41L3 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677  27 DVRCNVHLLHDSDIiGNEFPRTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHKHRYWLDLTRSINHvvknfKTESMTLHL 106
Cdd:cd17203   1 NMQCKVTLLDGSEY-TCEVEKRSKGQVLFDKVCEHLNLLEKDYFGLTYRDSENQKNWLDPAKEIKK-----QIRSGAWQF 74

                        90
                ....*....|
gi 17505677 107 RF--RYYPSD 114
Cdd:cd17203  75 SFnvKFYPPD 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF and pleckstrin domain-containing protein 1 (FARP1); 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. As a novel downstream signaling partner of Rif, FARP1 is involved in the regulation of semaphorin signaling in neurons. FARP1 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).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17505677  44 EFPRTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHKHRYWLDLTRSINHVVKNFKTESMTLHLRFryYPSD 114
Cdd:cd17189  16 EVPQRAPGKVLLDAVCSHLNLVEGDYFGLEFQDHRKVMVWLDLLKPIVKQIRRPKHVVLRFVVKF--FPPD 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 2 (EPB41L2) and similar proteins; EPB41L2, also termed generally expressed protein 4.1 (4.1G), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L2 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677  28 VRCNVHLLhDSDIIGNEFPRTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHKHRYWLDLTRSINHVVKNFkteSMTLHLR 107
Cdd:cd17202   2 VLCKVTLL-DGTEYSCDLEKRAKGQVLFDKVCEHLNLLEKDYFGLLYQVSANQKNWLDSTKEIKRQIRRL---PWLFTFN 77

                ....*..
gi 17505677 108 FRYYPSD 114
Cdd:cd17202  78 VKFYPPD 84

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677  30 CNVHLLHDSDIiGNEFPRTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHKHRYWLDLTRSINhvvKNFKTESMTLHLRFR 109
Cdd:cd17201   4 CKVTLLDGSEY-ECEVEKHARGQVLFDTVCEHLNLLEKDYFGLTFCDTESQKNWLDPSKEIK---KQIRSGPWHFAFTVK 79

                ....*
gi 17505677 110 YYPSD 114
Cdd:cd17201  80 FYPPD 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).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677  29 RCNVHLLHDS--DIIGNefPRTQSAQtILDYVCQLKHIQEKDFLGLRYQDHHKHRYWLDLTRS-INHVV-KNFKTESMTL 104
Cdd:cd17103   4 RCQVVLLDDRrlEILVQ--PKLLAGD-LLDLVASHFNLKEKEYFGLAYEDETGHYNWLQLDKRvLDHEFpKKWSSGPLVL 80

                ....*..
gi 17505677 105 HLRFRYY 111
Cdd:cd17103  81 HFAVKFY 87

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677  36 HDSDIignEFP--RTQSAQTILDYVCQLKHIQEKDFLGLRYQDHHKHRYWLDLTRSI-NHVVKnfKTESMTLHLRFRYYP 112
Cdd:cd17097   8 MDAEL---EFSikPKAKGRELFDLVCRTIGLRETWYFGLQYENKKGRVAWLKPDKKVlTQDVS--KNNTLKFFFLVKFYP 82

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).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17505677  29 RCNVHLLHDSDIIGNEFPRTQsAQTILDYVCQLKHIQEKDFLGLRYQDHHKHRYWLDLTRSINHVVKNFKTESMTLHLRF 108
Cdd:cd17199   4 RCQVHLLDDRKLELLVQPKLL-AKELLDLVASHFNLKEKEYFGIAFTDETGHLNWLQLDRRVLEHDFPKKSGPVVLYFCV 82

                ...
gi 17505677 109 RYY 111
Cdd:cd17199  83 RFY 85