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 569003231 147 GVDLHPVYGENKSEYFLGLTPSGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDC--NETSFFFEARSKTACKHL 224
Cdd:cd13186    1 GVDLHPVKGEDGNEYFLGLTPTGILVFENKTKIGLFFWPRITKLDFKGKKLKLVVKEKDDqeQEHTFVFRLPNKKACKHL 80

                         90
                 ....*....|..
gi 569003231 225 WKCSVEHHTFFR 236
Cdd:cd13186   81 WKCAVEHHAFFR 92

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 569003231  251 KFGSISYKHRYSGRTALQMSRDLSIQLpRPNQNVVRSRSKTYPKR 295
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 569003231 147 GVDLHPVYGENKSEYFLGLTPSGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDC--NETSFFFEARSKTACKHL 224
Cdd:cd13186    1 GVDLHPVKGEDGNEYFLGLTPTGILVFENKTKIGLFFWPRITKLDFKGKKLKLVVKEKDDqeQEHTFVFRLPNKKACKHL 80

                         90
                 ....*....|..
gi 569003231 225 WKCSVEHHTFFR 236
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 569003231   41 EDPCKLKEEITRYQFFLQVKQDALQGRLPCPVNIAAQMGAYAIQAELGDHDPYKHTAGYVSEYRFVPDQ------KEELE 114
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQllrkmkSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 569003231  115 EAIERIHKTLMGQAPSEAELNYLRTAKSLEMYGVDLH 151
Cdd:pfam00373  81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569003231  156 ENKSEYFLGLTPSGVVVY-KNKKQVGKYFWPRITKVHFKETQFELRVLGKDCnETSFFFEARSKTACKHLWKCSVEHHTF 234
Cdd:pfam09380   2 KEGTDLWLGVSAKGILVYeDNNKILNLFPWREIRKISFKRKKFLIKLRDKSS-EETLGFYTESSRACKYLWKLCVEQHTF 80

                  ..
gi 569003231  235 FR 236
Cdd:pfam09380  81 FR 82

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 569003231 147 GVDLHPVYGENKSEYFLGLTPSGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDC--NETSFFFEARSKTACKHL 224
Cdd:cd13186    1 GVDLHPVKGEDGNEYFLGLTPTGILVFENKTKIGLFFWPRITKLDFKGKKLKLVVKEKDDqeQEHTFVFRLPNKKACKHL 80

                         90
                 ....*....|..
gi 569003231 225 WKCSVEHHTFFR 236
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 569003231   41 EDPCKLKEEITRYQFFLQVKQDALQGRLPCPVNIAAQMGAYAIQAELGDHDPYKHTAGYVSEYRFVPDQ------KEELE 114
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQllrkmkSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 569003231  115 EAIERIHKTLMGQAPSEAELNYLRTAKSLEMYGVDLH 151
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 569003231 132 AELNYLRTAKSLEMYGVDLHPVYGENKSEYFLGLTPSGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDCNETSF 211
Cdd:cd13192    1 AEDNFLRKAATLETYGVDPHPVKDHRGNQLYLGFTHTGIVTFQGGKRVHHFRWNDITKFNYEGKMFILHVMQKEEKKHTL 80

                         90       100
                 ....*....|....*....|....*
gi 569003231 212 FFEARSKTACKHLWKCSVEHHTFFR 236
Cdd:cd13192   81 GFKCPTPAACKHLWKCAVEQQAFYT 105

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 569003231 146 YGVDLHPVYGENKSEYFLGLTPSGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDCN--ETSFFFEARSKTACKH 223
Cdd:cd13184    1 YGVDLHPAKDSEGVDIMLGVCSSGLLVYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEqyETTIGFKLPNHRAAKR 80

                         90
                 ....*....|....
gi 569003231 224 LWKCSVEHHTFFRM 237
Cdd:cd13184   81 LWKVCVEHHTFFRL 94

FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569003231 147 GVDLHPVY--GENKSEYFLGLTPSGVVVYKN--KKQVGKYFWPRITKVHFKE-TQFELRVLGKDcNETSFFFEArSKTAC 221
Cdd:cd00836    1 GVEFFPVKdkSKKGSPIILGVNPEGISVYDEltGQPLVLFPWPNIKKISFSGaKKFTIVVADED-KQSKLLFQT-PSRQA 78

                         90
                 ....*....|....*
gi 569003231 222 KHLWKCSVEHHTFFR 236
Cdd:cd00836   79 KEIWKLIVGYHRFLL 93

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
                 ....*....|....*....|....*....|....
gi 569003231   9 YWLDPAKTLAEHKELIntGPPYTLYFGIKFYAED 42
Cdd:cd17107   60 HWLDPAKTLSEQLKLI--GPPYTLYFGVKFYAED 91

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 14 and 21 (PTPN14 and 21); This CD contains PTP members: pez/PTPN14 and PTPN21. A number of mutations in Pez have been shown to be associated with breast and colorectal cancer. The PTPN protein family belong to larger family of PTPs. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. The members are composed of a N-terminal FERM domain and a C-terminal PTP catalytic 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. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. 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 569003231 146 YGVDLHPVYGENKSEYFLGLTPSGVVV-YKNKKQVGKYFWPRITKVHFKETQFELRvLGKDCNETSFFFEArSKTAcKHL 224
Cdd:cd13188    1 YGEESFPAKDEQGNEVLIGASLEGIFVkHDNGRPPVFFRWEDIKNVINHKRTFSIE-CQNSEETVQFQFED-AETA-KYV 77

                         90
                 ....*....|...
gi 569003231 225 WKCSVEHHTFFRM 237
Cdd:cd13188   78 WKLCVLQHKFYRQ 90

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like 5 (EPB41L5) and similar proteins; This family includes FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like proteins, EPB41L5 and EPB41L4B. EPB41L5 is a mesenchymal-specific protein that is an integral component of the ARF6-based pathway. 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. Both EPB41L5 and EPB41L4B 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
                 ....*....|....*....|....*....|.
gi 569003231   9 YWLDPAKTLaehKELINTGPPYTLYFGIKFY 39
Cdd:cd17108   54 HWLDPTKKI---KKQVKIGPPYTLRFRVKFY 81

FERM domain C-lobe/F3 of the ERM family; The ERM family includes ezrin, radixin, moesin and merlin. They are composed of a N-terminal FERM (ERM) domain (also called N-ERMAD (N-terminal ERM association domain)), a coiled coil region (CRR), and a C-terminal domain CERMAD (C-terminal ERM association domain) which has an F-actin-binding site (ABD). Two actin-binding sites have been identified in the middle and N-terminal domains. Merlin is structurally similar to the ERM proteins, but instead of an actin-binding domain (ABD), it contains a C-terminal domain (CTD), just like the proteins from the 4.1 family. Activated ezrin, radixin and moesin are thought to be involved in the linking of actin filaments to CD43, CD44, ICAM1-3 cell adhesion molecules, various membrane channels and receptors, such as the Na+/H+ exchanger-3 (NHE3), cystic fibrosis transmembrane conductance regulator (CFTR), and the beta2-adrenergic receptor. The ERM proteins 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 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 of ERM 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 569003231 145 MYGVDLHPVYGENKSEYFLGLTPSGVVVYK-NKKQVGK--YFWPRITKVHFKETQFELRVLGKDCNETSFFFEaRSKTaC 221
Cdd:cd13194    1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEpDNKLTPKigFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSP-RLRI-N 78

                         90
                 ....*....|....
gi 569003231 222 KHLWKCSVEHHTFF 235
Cdd:cd13194   79 KRILDLCMGNHELY 92

FERM domain C-lobe of FERM domain containing 1 and 6 proteins; FRMD6 (also called willin and hEx/human expanded) is localized throughout the cytoplasm or along the plasma membrane. The Drosophilla protein Ex is a regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in organ size control and is tumor suppression by restricting proliferation and promoting apoptosis. Surprisingly, hEx is thought to function independently of the Hippo pathway. Instead it is hypothesized that hEx inhibits progression through the S phase of the cell cycle by upregulating p21(Cip1) and downregulating Cyclin A. It is also implicated in the progression of Alzheimer disease. Not much is known about FRMD1 to date. Both FRMD1 and FRMD6 contains a single 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 569003231 146 YGVDLHPVYgENKSEY----FLGLTPSGVVVYKN---KKQV-GKYFWPRITKVHFKETQFELRVLGKdcnETSFFFEARS 217
Cdd:cd13185    3 LNAHLYRLR-KSKKETpgsvLLGITAKGIQIYQEsdgEQQLlRTFPWSNIGKLSFDRKKFEIRPEGS---LRKLTYYTSS 78

                         90       100
                 ....*....|....*....|.
gi 569003231 218 KTACKHLWK-CSVEHHTFFRM 237
Cdd:cd13185   79 DEKSKYLLAlCRETHQFSMAI 99