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 569003235     1 MGAYAIQAELGDHDPYKH-TAGYVSEYRFVPDQ------KEELEEAIERIHKTLMGQAPSEAELNYLRTAKSLEMYGVDL 73
Cdd:smart00295 121 LAALALQAEFGDYDEELHdLRGELSLKRFLPKQlldsrkLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVEL 200

                   .
gi 569003235    74 H 74
Cdd:smart00295 201 F 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 569003235     1 MGAYAIQAELGDHDPYKH-TAGYVSEYRFVPDQ------KEELEEAIERIHKTLMGQAPSEAELNYLRTAKSLEMYGVDL 73
Cdd:smart00295 121 LAALALQAEFGDYDEELHdLRGELSLKRFLPKQlldsrkLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVEL 200

                   .
gi 569003235    74 H 74
Cdd:smart00295 201 F 201

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569003235   79 ENKSEYFLGLTPSGVVVY-KNKKQVGKYFWPRITKVHFKETQFELRVLGKDCnETSFFFEARSKTACKHLWKCSVEHHTF 157
Cdd:pfam09380   2 KEGTDLWLGVSAKGILVYeDNNKILNLFPWREIRKISFKRKKFLIKLRDKSS-EETLGFYTESSRACKYLWKLCVEQHTF 80

                  ..
gi 569003235  158 FR 159
Cdd:pfam09380  81 FR 82

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 569003235  174 KFGSISYKHRYSGRTALQMSRDLSIQLpRPNQNVVRSRSKTYPKR 218
Cdd:pfam08736   1 KFFSLGSKFRYSGRTQKQTVEDSSEIL-RPQPEFERSPSKRYPSR 44

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 569003235  55 AELNYLRTAKSLEMYGVDLHPVYGENKSEYFLGLTPSGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDCNETSF 134
Cdd:cd13192    1 AEDNFLRKAATLETYGVDPHPVKDHRGNQLYLGFTHTGIVTFQGGKRVHHFRWNDITKFNYEGKMFILHVMQKEEKKHTL 80

                         90       100
                 ....*....|....*....|....*
gi 569003235 135 FFEARSKTACKHLWKCSVEHHTFFR 159
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 569003235  69 YGVDLHPVYGENKSEYFLGLTPSGVVVYKNKKQVGKYFWPRITKVHFKETQFELRVLGKDCN--ETSFFFEARSKTACKH 146
Cdd:cd13184    1 YGVDLHPAKDSEGVDIMLGVCSSGLLVYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFEqyETTIGFKLPNHRAAKR 80

                         90
                 ....*....|....
gi 569003235 147 LWKCSVEHHTFFRM 160
Cdd:cd13184   81 LWKVCVEHHTFFRL 94

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569003235   1 MGAYAIQAELGDHDPYKHTAGYVSEYRFVPDQ------KEELEEAIERIHKTLMGQAPSEAELNYLRTAKSL 66
Cdd:cd14473   28 LAALALQAEYGDYDPSEHKPKYLSLKRFLPKQllkqrkPEEWEKRIVELHKKLRGLSPAEAKLKYLKIARKL 99

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569003235    1 MGAYAIQAELGDHDPYKHTAGYVSEYRFVPDQ------KEELEEAIERIHKTLMGQAPSEAELNYLRTAKSLEMYGVDLH 74
Cdd:pfam00373  38 LAALQLQAEFGDYQPSSHTSEYLSLESFLPKQllrkmkSKELEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

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 569003235  62 TAKSLEMYGVDLHPVYGENKSEYFLGLTPSGVVVYKNKKQVGKYFWPRITKVHFKETQF------ELRVLGKDCNEtsFF 135
Cdd:cd13193    2 TARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFliklhpEAYGSYKDTVE--FS 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 569003235 136 FEARSktACKHLWKCSVEHHTFFRMPDTESNSLSR 170
Cdd:cd13193   80 FESRN--ECKSFWKKCIEHHAFFRCSEVPKPPSPK 112

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 569003235  69 YGVDLHPVYGENKSEYFLGLTPSGVVV-YKNKKQVGKYFWPRITKVHFKETQFELRvLGKDCNETSFFFEArSKTAcKHL 147
Cdd:cd13188    1 YGEESFPAKDEQGNEVLIGASLEGIFVkHDNGRPPVFFRWEDIKNVINHKRTFSIE-CQNSEETVQFQFED-AETA-KYV 77

                         90
                 ....*....|...
gi 569003235 148 WKCSVEHHTFFRM 160
Cdd:cd13188   78 WKLCVLQHKFYRQ 90

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 569003235  67 EMYGVDLHPVYgENKSEY----FLGLTPSGVVVYKN---KKQV-GKYFWPRITKVHFKETQFELRVLGKdcnETSFFFEA 138
Cdd:cd13185    1 EDLNAHLYRLR-KSKKETpgsvLLGITAKGIQIYQEsdgEQQLlRTFPWSNIGKLSFDRKKFEIRPEGS---LRKLTYYT 76

                         90       100
                 ....*....|....*....|...
gi 569003235 139 RSKTACKHLWK-CSVEHHTFFRM 160
Cdd:cd13185   77 SSDEKSKYLLAlCRETHQFSMAI 99