FERM domain C-lobe of Novel band 4.1-like protein 4 and 5 (NBL4 and 5); NBL4 (also called Erythrocyte protein band 4.1-like 4; Epb4 1l4) plays a role the beta-catenin/Tcf signaling pathway and is thought to be involved in establishing the cell polarity or proliferation. NBL4 may be also involved in adhesion, in cell motility and/or in cell-to-cell communication. No role for NBL5 has been proposed to date. Both NBL4 and NBL5 contain a N-terminal FERM domain which 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 is a member of the PH superfamily. 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 767936247 207 GVDLHPVYGENKSEYFLGLTPVGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDC--NETSFFFEARSKTACKHL 284
Cdd:cd13186    1 GVDLHPVKGEDGNEYFLGLTPTGILVFENKTKIGLFFWPRITKLDFKGKKLKLVVKEKDDqeQEHTFVFRLPNKKACKHL 80

                         90
                 ....*....|..
gi 767936247 285 WKCSVEHHTFFR 296
Cdd:cd13186   81 WKCAVEHHAFFR 92

FERM domain C-lobe of Novel band 4.1-like protein 4 and 5 (NBL4 and 5); NBL4 (also called Erythrocyte protein band 4.1-like 4; Epb4 1l4) plays a role the beta-catenin/Tcf signaling pathway and is thought to be involved in establishing the cell polarity or proliferation. NBL4 may be also involved in adhesion, in cell motility and/or in cell-to-cell communication. No role for NBL5 has been proposed to date. Both NBL4 and NBL5 contain a N-terminal FERM domain which 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 is a member of the PH superfamily. 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 767936247 207 GVDLHPVYGENKSEYFLGLTPVGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDC--NETSFFFEARSKTACKHL 284
Cdd:cd13186    1 GVDLHPVKGEDGNEYFLGLTPTGILVFENKTKIGLFFWPRITKLDFKGKKLKLVVKEKDDqeQEHTFVFRLPNKKACKHL 80

                         90
                 ....*....|..
gi 767936247 285 WKCSVEHHTFFR 296
Cdd:cd13186   81 WKCAVEHHAFFR 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  101 EDPCKLKEEITRYQFFLQVKQDVLQGRLPCPVNTAAQLGAYAIQSELGDYDPYKHTAGYVSEYRFVPDQ------KEELE 174
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQllrkmkSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 767936247  175 EAIERIHKTLMGQIPSEAELNYLRTAKSLEMYGVDLH 211
Cdd:pfam00373  81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 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 767936247  311 KFGSIRYKHRYSGRTALQMSRDLSIQLpRPDQNVTRSRSKTYPKR 355
Cdd:pfam08736   1 KFFSLGSKFRYSGRTQKQTVEDSSEIL-RPQPEFERSPSKRYPSR 44

FERM domain C-lobe of Novel band 4.1-like protein 4 and 5 (NBL4 and 5); NBL4 (also called Erythrocyte protein band 4.1-like 4; Epb4 1l4) plays a role the beta-catenin/Tcf signaling pathway and is thought to be involved in establishing the cell polarity or proliferation. NBL4 may be also involved in adhesion, in cell motility and/or in cell-to-cell communication. No role for NBL5 has been proposed to date. Both NBL4 and NBL5 contain a N-terminal FERM domain which 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 is a member of the PH superfamily. 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 767936247 207 GVDLHPVYGENKSEYFLGLTPVGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDC--NETSFFFEARSKTACKHL 284
Cdd:cd13186    1 GVDLHPVKGEDGNEYFLGLTPTGILVFENKTKIGLFFWPRITKLDFKGKKLKLVVKEKDDqeQEHTFVFRLPNKKACKHL 80

                         90
                 ....*....|..
gi 767936247 285 WKCSVEHHTFFR 296
Cdd:cd13186   81 WKCAVEHHAFFR 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  101 EDPCKLKEEITRYQFFLQVKQDVLQGRLPCPVNTAAQLGAYAIQSELGDYDPYKHTAGYVSEYRFVPDQ------KEELE 174
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQllrkmkSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 767936247  175 EAIERIHKTLMGQIPSEAELNYLRTAKSLEMYGVDLH 211
Cdd:pfam00373  81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

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 767936247 192 AELNYLRTAKSLEMYGVDLHPVYGENKSEYFLGLTPVGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDCNETSF 271
Cdd:cd13192    1 AEDNFLRKAATLETYGVDPHPVKDHRGNQLYLGFTHTGIVTFQGGKRVHHFRWNDITKFNYEGKMFILHVMQKEEKKHTL 80

                         90       100
                 ....*....|....*....|....*
gi 767936247 272 FFEARSKTACKHLWKCSVEHHTFFR 296
Cdd:cd13192   81 GFKCPTPAACKHLWKCAVEQQAFYT 105

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 3 and 4 (PTPN4 and PTPN3); PTPN4 (also called PTPMEG, protein tyrosine phosphatase, megakaryocyte) is a cytoplasmic protein-tyrosine phosphatase (PTP) thought to play a role in cerebellar function. PTPMEG-knockout mice have impaired memory formation and cerebellar long-term depression. PTPN3/PTPH1 is a membrane-associated PTP that is implicated in regulating tyrosine phosphorylation of growth factor receptors, p97 VCP (valosin-containing protein, or Cdc48 in Saccharomyces cerevisiae), and HBV (Hepatitis B Virus) gene expression; it is mutated in a subset of colon cancers. PTPMEG and PTPN3/PTPH1 contains a N-terminal FERM domain, a middle PDZ domain, and a C-terminal phosphatase domain. PTP1/Tyrosine-protein phosphatase 1 from nematodes and a FERM_C repeat 1 from Tetraodon nigroviridis are also included in this cd. 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 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 767936247 205 MYGVDLHPVYGENKSEYFLGLTPVGVVVYKNKKQVGKYFWPRITKVHFKETQF--ELRVLGKDCNETSFFFEARSKTACK 282
Cdd:cd13189    1 LYGVELHSARDSNNLELQIGVSSAGILVFQNGIRINTFPWSKIVKISFKRKQFfiQLRREPNESRDTILGFNMLSYRACK 80

                         90
                 ....*....|....*
gi 767936247 283 HLWKCSVEHHTFFRM 297
Cdd:cd13189   81 NLWKSCVEHHTFFRL 95

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 3 (PTPN3) and similar proteins; This family includes two tyrosine-protein phosphatase non-receptors, PTPN3 and PTPN4, both of which belong 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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  13 CEVLLLDESKLTLTtqqqgIKKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTY---WLDPAKTLaehKELINTGPP 89
Cdd:cd17100    4 CIVHFLDDTEQTFE-----VEKRDKGQVLLDKVFNHLELVEKDYFGLQFSDDSPATDsmrWLDPLKPI---RKQIKGGPP 75

                         90
                 ....*....|.
gi 767936247  90 YTLYFGIKFYA 100
Cdd:cd17100   76 YYLNFRVKFYV 86

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 767936247 206 YGVDLHPVYGENKSEYFLGLTPVGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDCN--ETSFFFEARSKTACKH 283
Cdd:cd13184    1 YGVDLHPAKDSEGVDIMLGVCSSGLLVYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEqyETTIGFKLPNHRAAKR 80

                         90
                 ....*....|....
gi 767936247 284 LWKCSVEHHTFFRM 297
Cdd:cd13184   81 LWKVCVEHHTFFRL 94

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767936247   15 VLLLDESKLTLTTQqqgikKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAEH 80
Cdd:pfam09379   1 VRLLDGTVLEFDVQ-----PKATGQVLLDQVCNHLNLKEKDYFGLQFLDDNGEHRWLDLSKRLSKQ 61

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  13 CEVLLLDESKLTLTTQQQGIkkstkGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAEHKELINTgppYTL 92
Cdd:cd17098    3 VKVQMLDDTVHIFQVQQKAL-----GEVLFDQVCKHLNLLESDYFGLEFTDPEGNKCWLDPEKPILRQVKRPKD---VVF 74

                         90
                 ....*....|.
gi 767936247  93 YFGIKFYAEDP 103
Cdd:cd17098   75 KFVVKFYTPDP 85

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 767936247  13 CEVLLLDESKLTLTtqqqgIKKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKtlaEHKELINTGpPYTL 92
Cdd:cd17201    4 CKVTLLDGSEYECE-----VEKHARGQVLFDTVCEHLNLLEKDYFGLTFCDTESQKNWLDPSK---EIKKQIRSG-PWHF 74

                         90
                 ....*....|
gi 767936247  93 YFGIKFYAED 102
Cdd:cd17201   75 AFTVKFYPPD 84

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 767936247 199 TAKSLEMYGVDLHPVYGENKSEYFLGLTPVGVVVYKNKKQVGKYFWPRITKVHFKETQF------ELRVLGKDCNEtsFF 272
Cdd:cd13193    2 TARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFliklhpEAYGSYKDTVE--FS 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 767936247 273 FEARSktACKHLWKCSVEHHTFFRMPENESNSLSR 307
Cdd:cd13193   80 FESRN--ECKSFWKKCIEHHAFFRCSEVPKPPSPK 112

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 767936247  13 CEVLLLDESKLTLTtqqqgIKKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLaehKELINTGPPYTL 92
Cdd:cd17205    5 CRVSLLDGTDVSVD-----LPKKAKGQELFEQIMYHLDLIEKDYFGLRFMDSAQVAHWLDVTKSI---KKQVKIGPPYCL 76

                         90
                 ....*....|
gi 767936247  93 YFGIKFYAED 102
Cdd:cd17205   77 HLRVKFYSSE 86

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 767936247  13 CEVLLLDESKLTLTtqqqgIKKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLaeHKELINTgpPYTL 92
Cdd:cd17202    4 CKVTLLDGTEYSCD-----LEKRAKGQVLFDKVCEHLNLLEKDYFGLLYQVSANQKNWLDSTKEI--KRQIRRL--PWLF 74

                         90
                 ....*....|
gi 767936247  93 YFGIKFYAED 102
Cdd:cd17202   75 TFNVKFYPPD 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 767936247  13 CEVLLLDESKLTLTTQqqgikKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAEHK-ELINTGPPYT 91
Cdd:cd17103    5 CQVVLLDDRRLEILVQ-----PKLLAGDLLDLVASHFNLKEKEYFGLAYEDETGHYNWLQLDKRVLDHEfPKKWSSGPLV 79

                         90
                 ....*....|
gi 767936247  92 LYFGIKFYAE 101
Cdd:cd17103   80 LHFAVKFYVE 89

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 767936247  311 KFGSIRYKHRYSGRTALQMSRDLSIQLpRPDQNVTRSRSKTYPKR 355
Cdd:pfam08736   1 KFFSLGSKFRYSGRTQKQTVEDSSEIL-RPQPEFERSPSKRYPSR 44

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 767936247  13 CEVLLLDESKLTLTTQQQGIKKStkgsvVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAEHKELINTGpPYTL 92
Cdd:cd17199    5 CQVHLLDDRKLELLVQPKLLAKE-----LLDLVASHFNLKEKEYFGIAFTDETGHLNWLQLDRRVLEHDFPKKSG-PVVL 78

                 ....*....
gi 767936247  93 YFGIKFYAE 101
Cdd:cd17199   79 YFCVRFYIE 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  32 IKKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAehKELINTGPPYTLYFGIKFYAE 101
Cdd:cd17097   16 IKPKAKGRELFDLVCRTIGLRETWYFGLQYENKKGRVAWLKPDKKVL--TQDVSKNNTLKFFFLVKFYPE 83

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  14 EVLLLDESKLTLTTQQQGikkstKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAEHkelINTGPPYTLY 93
Cdd:cd17189    4 KVQMLDDTQEVFEVPQRA-----PGKVLLDAVCSHLNLVEGDYFGLEFQDHRKVMVWLDLLKPIVKQ---IRRPKHVVLR 75

                 ....*....
gi 767936247  94 FGIKFYAED 102
Cdd:cd17189   76 FVVKFFPPD 84

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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  11 FYCEVLLLDESKLTLTTQQqgikKSTkGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAEH-KELINTGpp 89
Cdd:cd17188    2 LHLKVQFLDDSQKVFVVDQ----KST-GKDLFNMSCSHLNLVEKEYFGLEFRNHAGNNVWLELLKPITKQiKNPKELI-- 74

                         90
                 ....*....|....
gi 767936247  90 ytLYFGIKFYAEDP 103
Cdd:cd17188   75 --FKFTVKFFPVDP 86

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM and PDZ domain-containing protein 2 (FRMPD2); FRMPD2, also termed PDZ domain-containing protein 4 (PDZK4), or PDZ domain-containing protein 5C (PDZD5C), is a potential scaffold protein involved in basolateral membrane targeting in epithelial cells. It interacts with nucleotide-binding oligomerization domain-2 (NOD2) through leucine-rich repeats and forms a complex with the membrane-associated protein ERBB2IP. FRMPD2 contains an N-terminal KIND domain, a FERM domain and three PDZ 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 767936247  36 TKGSVVLDHVFHHVNLVEIDYFGLRYCDrSHQTYWLDPAKTL-----------AEHKELINTgppYTLYFGIKFYAED 102
Cdd:cd17196   22 SRVRDVFNMVVAFANLVEHFYFGLAYMK-GKEFFFLDHETKLhkvapegwkdqSKKKTSIVN---FTLFLRIKFFVDN 95

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 13 (PTPN13); PTPN13, also termed Fas-associated protein-tyrosine phosphatase 1 (FAP-1), or PTP-BAS, or protein-tyrosine phosphatase 1E (PTP-E1 or PTPE1), or protein-tyrosine phosphatase PTPL1, belongs to the non-transmembrane FERM-containing protein-tyrosine phosphatase (PTP) subfamily characterized by a KIND domain, a FERM domain, five PDZ domains, 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). PTPN13 interacts with a variety of ligands, suggests an important role as a scaffolding protein. It is also involved in the regulation of apoptosis, cytokinesis and cell cycle progression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  15 VLLLDESKLTLTTQQQGIKKStkgsvVLDHVFHHVNLVEIDYFGLRYCdRSHQTYWLDPAKTLA---------EHKELIN 85
Cdd:cd17195    6 IMLLSGQRLELTCDTKSTCKD-----VFDMVVAHIGLVEHHLFALAYL-KDNEFFFVDPDLKLSkvapegwkeEPKKKNK 79

                         90
                 ....*....|....*..
gi 767936247  86 TGPPYTLYFGIKFYAED 102
Cdd:cd17195   80 MTVNFTLFFRIKFFVDD 96

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 13 (PTPN13) and similar proteins; This family includes tyrosine-protein phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and FERM domain-containing proteins FRMD1 and FRMD6. All family members 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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  15 VLLLDESKLTLTTQqqgikKSTKGSVVLDHVFHHVNLVEIDYFGLrycdrSHQT----YWLDPAKTLA---------EHK 81
Cdd:cd17101    6 VVLLNGQRLQVAVD-----VKTTVQDLFDQVCDHLGLQETELFGL-----AVLKdgeyFFLDPDTKLSkyapkgwksEAK 75

                         90       100
                 ....*....|....*....|.
gi 767936247  82 ELINTG-PPYTLYFGIKFYAE 101
Cdd:cd17101   76 KGLKGGkPVFTLYFRVKFYVD 96

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins, Ezrin, Radixin, and Moesin; The ezrin-radixin-moesin (ERM) family includes a group of closely related 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. 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).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767936247  32 IKKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAEHKelINTGPPYTLYFGIKFYAE 101
Cdd:cd17187   16 IQPNTTGKQLFDQVVKTIGLREIWFFGLQYVDSKGYSTWLKLNKKVLSQD--VKKENPLQFKFRAKFYPE 83

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in radixin and similar proteins; Radixin 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 the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Radixin plays important roles in cell polarity, cell motility, invasion and tumor progression. It mediates the binding of F-actin to the plasma membrane after a conformational activation through Akt2-dependent phosphorylation at Thr564. It is also involved in reversal learning and short-term memory by regulating synaptic GABAA receptor density.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767936247  31 GIKKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAEHKelINTGPPYTLYFGIKFYAE 101
Cdd:cd17238   15 AIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTQQD--VKKENPLQFKFRAKFFPE 83

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767936247  31 GIKKSTKGSVVLDHVFHHVNLVEIDYFGLRYCDRSHQTYWLDPAKTLAEHKelINTGPPYTLYFGIKFYAE 101
Cdd:cd17237   16 AIQPNTTGKQLFDQVVKTIGLREVWFFGLQYQDTKGFSTWLKLNKKVTAQD--VRKESPLLFKFRAKFYPE 84