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 221379142    60 CRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDA-NHVKHWLDPTKPIKKQVKIGPPYTFRLKVKFY 138
Cdd:smart00295   2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPdEDLRHWLDPAKTLLDQDVKSEPLTLYFRVKFY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142   139 SSEPNTLREELTRY-LFFLQLKQDLLEGRLDCPEDKATELCALALQSELGDYDNQEHSAAT-VSEFRFVPEQT------E 210
Cdd:smart00295  82 PPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGeLSLKRFLPKQLldsrklK 161

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 221379142   211 DLEIAILDEYKTCRGLTPAQAETAFLNKAKWLDMYGVDMH 250
Cdd:smart00295 162 EWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

BDLF3; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142 771 SNATFVSGFSAPLTPPSSLPANLNNTGSGCNTTLTSVTTISTPSSPTATVSTTASE-SVAPALSNASAAEILINEIFINN 849
Cdd:PHA03255  32 ASAGNVTGTTAVTTPSPSASGPSTNQSTTLTTTSAPITTTAILSTNTTTVTSTGTTvTPVPTTSNASTINVTTKVTAQNI 111

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142 850 IINNNASGSITAETA-AKPAGSSTPSAGTLLFSTLSEQERLESQKTNqqmnqslNLNQNHSEVDAPPSEK 918
Cdd:PHA03255 112 TATEAGTGTSTGVTSnVTTRSSSTTSATTRITNATTLAPTLSSKGTS-------NATKTTAELPTVPDER 174

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 221379142    60 CRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDA-NHVKHWLDPTKPIKKQVKIGPPYTFRLKVKFY 138
Cdd:smart00295   2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPdEDLRHWLDPAKTLLDQDVKSEPLTLYFRVKFY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142   139 SSEPNTLREELTRY-LFFLQLKQDLLEGRLDCPEDKATELCALALQSELGDYDNQEHSAAT-VSEFRFVPEQT------E 210
Cdd:smart00295  82 PPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGeLSLKRFLPKQLldsrklK 161

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 221379142   211 DLEIAILDEYKTCRGLTPAQAETAFLNKAKWLDMYGVDMH 250
Cdd:smart00295 162 EWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142  142 PNTLREELTRYLFFLQLKQDLLEGRLDCPEDKATELCALALQSELGDYDNQEHSAATVSEFRFVPEQ------TEDLEIA 215
Cdd:pfam00373   3 ELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQllrkmkSKELEKR 82

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 221379142  216 ILDEYKTCRGLTPAQAETAFLNKAKWLDMYGVDMH 250
Cdd:pfam00373  83 VLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 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 221379142  352 NFFRMGSRFRYSGRTEFQTTQQSRA--RRTVQFERRPSQRFASR 393
Cdd:pfam08736   1 KFFSLGSKFRYSGRTQKQTVEDSSEilRPQPEFERSPSKRYPSR 44

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142    60 CRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDA-NHVKHWLDPTKPIKKQVKIGPPYTFRLKVKFY 138
Cdd:smart00295   2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPdEDLRHWLDPAKTLLDQDVKSEPLTLYFRVKFY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142   139 SSEPNTLREELTRY-LFFLQLKQDLLEGRLDCPEDKATELCALALQSELGDYDNQEHSAAT-VSEFRFVPEQT------E 210
Cdd:smart00295  82 PPDPNQLKEDPTRLnLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGeLSLKRFLPKQLldsrklK 161

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 221379142   211 DLEIAILDEYKTCRGLTPAQAETAFLNKAKWLDMYGVDMH 250
Cdd:smart00295 162 EWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

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 221379142  58 IDCRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQVKIGPPYTFRLKVKF 137
Cdd:cd17205    3 ITCRVSLLDGTDVSVDLPKKAKGQELFEQIMYHLDLIEKDYFGLRFMDSAQVAHWLDVTKSIKKQVKIGPPYCLHLRVKF 82

                 ....
gi 221379142 138 YSSE 141
Cdd:cd17205   83 YSSE 86

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 221379142 150 TRYLFFLQLKQDLLEGRLDCPEDKATELCALALQSELGDYDNQEHSAATVSEFRFVPEQT------EDLEIAILDEYKTC 223
Cdd:cd14473    1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLlkqrkpEEWEKRIVELHKKL 80

                         90
                 ....*....|....*....
gi 221379142 224 RGLTPAQAETAFLNKAKWL 242
Cdd:cd14473   81 RGLSPAEAKLKYLKIARKL 99

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142  58 IDCRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQVKIGPPYTFRLKVKF 137
Cdd:cd01765    1 ISCRVRLLDGTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEDNDGQKHWLDLDKKISKQLKRSGPYQFYFRVKF 80

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 221379142  60 CRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMD---ANHVKHWLDPTKPIKKQVKIGPPYTFRLKVK 136
Cdd:cd17100    4 CIVHFLDDTEQTFEVEKRDKGQVLLDKVFNHLELVEKDYFGLQFSDdspATDSMRWLDPLKPIRKQIKGGPPYYLNFRVK 83

                 ..
gi 221379142 137 FY 138
Cdd:cd17100   84 FY 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 3 (FRMD3) and similar proteins; FRMD3, also termed band 4.1-like protein 4O, or ovary type protein 4.1 (4.1O), belongs to the 4.1 protein superfamily, which share the highly conserved membrane-association FERM 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). FRMD3 is involved in maintaining cell shape and integrity. It also functions as a tumour suppressor in non-small cell lung carcinoma (NSCLC). Some single nucleotide polymorphisms (SNPs) located in FRMD3 have been associated with diabetic kidney disease (DKD) in different ethnicities.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142  60 CRVILLDNTD-LSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQVKIGPPYTFRLKVKFY 138
Cdd:cd17102    3 CTIRLLDDSEvICCEFKKDTKGQFLLDYVCNYLNLLEKDYFGLRYVDTEKQRHWLDPNKSIYKQLKGVPPYVLCFRVKFY 82

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 221379142  58 IDCRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQVKIGPPYTFRLKVKF 137
Cdd:cd17098    1 LHVKVQMLDDTVHIFQVQQKALGEVLFDQVCKHLNLLESDYFGLEFTDPEGNKCWLDPEKPILRQVKRPKDVVFKFVVKF 80

                 ....*
gi 221379142 138 YSSEP 142
Cdd:cd17098   81 YTPDP 85

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 221379142 245 YGVDMHTVLGKDGCEYHLGLTPTGILVFERDQKIGLFFWPKISKLDFKKKKLTLIVIEDDDEgrEQEHTFVFRLYNEKAC 324
Cdd:cd13184    1 YGVDLHPAKDSEGVDIMLGVCSSGLLVYRDRLRINRFAWPKVLKISYKRNNFYIKIRPGEFE--QYETTIGFKLPNHRAA 78

                         90
                 ....*....|....*.
gi 221379142 325 KHLWKCAVEHHTFFRL 340
Cdd:cd13184   79 KRLWKVCVEHHTFFRL 94

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 221379142  58 IDCRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQVKIGpPYTFRLKVKF 137
Cdd:cd17201    2 AICKVTLLDGSEYECEVEKHARGQVLFDTVCEHLNLLEKDYFGLTFCDTESQKNWLDPSKEIKKQIRSG-PWHFAFTVKF 80

                 .
gi 221379142 138 Y 138
Cdd:cd17201   81 Y 81

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 221379142  60 CRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQVKIGpPYTFRLKVKFYS 139
Cdd:cd17203    4 CKVTLLDGSEYTCEVEKRSKGQVLFDKVCEHLNLLEKDYFGLTYRDSENQKNWLDPAKEIKKQIRSG-AWQFSFNVKFYP 82

                 ..
gi 221379142 140 SE 141
Cdd:cd17203   83 PD 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 221379142  58 IDCRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQVKiGPPYTFRLKVKF 137
Cdd:cd17202    2 VLCKVTLLDGTEYSCDLEKRAKGQVLFDKVCEHLNLLEKDYFGLLYQVSANQKNWLDSTKEIKRQIR-RLPWLFTFNVKF 80

                 ....
gi 221379142 138 YSSE 141
Cdd:cd17202   81 YPPD 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 4 (PTPN4); PTPN4, also termed protein-tyrosine phosphatase MEG1 (MEG) or PTPase-MEG1, belongs to the non-transmembrane FERM-containing protein-tyrosine phosphatase (PTP) subfamily characterized by a conserved N-terminal FERM domain, a PDZ domain, and a C-terminal PTP catalytic domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PTPN4 protects cells against apoptosis. It associates with the mitogen-activated protein kinase p38gamma (also known as MAPK12) to form a PTPN4-p38gamma complex that promotes cellular signaling, preventing cell death induction. It also inhibits tyrosine phosphorylation and subsequent cytoplasm translocation of TRIF-related adaptor molecule (TRAM, also known as TICAM2), resulting in the disturbance of TRAM-TRIF interaction. Moreover, PTPN4 negatively regulates cell proliferation and motility through dephosphorylation of CrkI.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142  60 CRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMD-ANHVKHWLDPTKPIKKQVKIGPPYTFRLKVKFY 138
Cdd:cd17194    4 CNILLLDNTVQAFKVNKHDQGQVLLDLVFKHLDLTERDYFGLQLADdSTDNPRWLDPNKPIRKQLKRGSPHNLNFRVKFF 83

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in E3 ubiquitin-protein ligase MYLIP and similar proteins; MYLIP, also termed inducible degrader of the LDL-receptor (Idol), or myosin regulatory light chain interacting protein (MIR), is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Its activity depends on E2 ubiquitin-conjugating enzymes of the UBE2D family, including UBE2D1, UBE2D2, UBE2D3, and UBE2D4. MYLIP stimulates clathrin-independent endocytosis and acts as a sterol-dependent inhibitor of cellular cholesterol uptake by binding directly to the cytoplasmic tail of the LDLR and promoting its ubiquitination via the UBE2D1/E1 complex. The ubiquitinated LDLR then enters the multivesicular body (MVB) protein-sorting pathway and is shuttled to the lysosome for degradation. Moreover, MYLIP has been identified as a novel ERM-like protein that affects cytoskeleton interactions regulating cell motility, such as neurite outgrowth. The ERM proteins includes ezrin, radixin, and moesin, which are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. MYLIP contains a FERM-domain and a C-terminal C3HC4-type RING-HC finger. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221379142  60 CRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQVKIGPPYTFRLKVKFY 138
Cdd:cd17104    3 CLVSQPDSVVIEVEVDPKANGQECLDKVCQKLGIIEKDYFGLQYTGPKGERLWLNLRNRISRQLPGPPPYRLRLRVKFF 81

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 221379142 246 GVDMHTVLGKD--GCEYHLGLTPTGILVFERD--QKIGLFFWPKISKLDFKKKKLTLIVIedDDEGREQEHTFVFRlynE 321
Cdd:cd00836    1 GVEFFPVKDKSkkGSPIILGVNPEGISVYDELtgQPLVLFPWPNIKKISFSGAKKFTIVV--ADEDKQSKLLFQTP---S 75

                         90
                 ....*....|....*...
gi 221379142 322 KACKHLWKCAVEHHTFFR 339
Cdd:cd00836   76 RQAKEIWKLIVGYHRFLL 93

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 221379142  61 RVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMD--ANHVkhWLDPTKPIKKQVKIGPPYTFRLKVKFY 138
Cdd:cd17188    5 KVQFLDDSQKVFVVDQKSTGKDLFNMSCSHLNLVEKEYFGLEFRNhaGNNV--WLELLKPITKQIKNPKELIFKFTVKFF 82

                 ....
gi 221379142 139 SSEP 142
Cdd:cd17188   83 PVDP 86

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptors PTPN14, PTPN21, and similar proteins; This family includes tyrosine-protein phosphatase non-receptors PTPN14 and PTPN21, both of which are protein-tyrosine phosphatase (PTP). They belong to the FERM family of PTPs characterized by a conserved N-terminal FERM domain and a C-terminal PTP catalytic domain with an intervening sequence containing an acidic region and a putative SH3 domain-binding sequence. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PTPN14 plays a role in the nucleus during cell proliferation. PTPN21 interacts with a Tec tyrosine kinase family member, the epithelial and endothelial tyrosine kinase (Etk, also known as Bmx), modulates Stat3 activation, and plays a role in the regulation of cell growth and differentiation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221379142  61 RVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQV-KIGPPYTFRLKVKFY 138
Cdd:cd17099    7 RIQLLDNTVLECTLSPESTGQDCLEYVAQRLELREIEYFGLRYVNKKGQLRWVDLEKPLKKQLdKHAHEPLLYFGVMFY 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Ezrin and similar proteins; Ezrin, also termed cytovillin, or villin-2, or p81, 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). Ezrin is a tyrosine kinase substrate that functions as a cross-linker between actin cytoskeleton and plasma membrane. It has been implicated in the regulation of the proliferation, apoptosis, adhesion, invasion, metastasis and angiogenesis of cancer cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142  58 IDCRVILLDnTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQ-VKIGPPYTFRLKVK 136
Cdd:cd17239    3 INVRVTTMD-AELEFAIQPNTTGKQLFDQVVKTIGLREVWYFGLQYVDNKGFPTWLKLDKKVSAQeVRKENPLQFKFRAK 81

                 ..
gi 221379142 137 FY 138
Cdd:cd17239   82 FY 83

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 221379142  60 CRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTK-------PIKKQvkiGPPYTFR 132
Cdd:cd17103    5 CQVVLLDDRRLEILVQPKLLAGDLLDLVASHFNLKEKEYFGLAYEDETGHYNWLQLDKrvldhefPKKWS---SGPLVLH 81

                 ....*.
gi 221379142 133 LKVKFY 138
Cdd:cd17103   82 FAVKFY 87

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 21 (PTPN21) and similar proteins; PTPN21, also termed protein-tyrosine phosphatase D1 (PTPD1), is a cytosolic non-receptor protein-tyrosine phosphatase (PTP) that belongs to the FERM family of PTPs characterized by a conserved N-terminal FERM domain and a C-terminal PTP catalytic domain with an intervening sequence containing an acidic region and a putative SH3 domain-binding sequence. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PTPN21 interacts with a Tec tyrosine kinase family member, the epithelial and endothelial tyrosine kinase (Etk, also known as Bmx), modulates Stat3 activation, and plays a role in the regulation of cell growth and differentiation. It also associates with and activates Src tyrosine kinase, and directs epidermal growth factor (EGF)/Src signaling to the nucleus through activating ERK1/2- and Elk1-dependent gene transcription. PTPD1-Src complex interacts a protein kinase A-anchoring protein AKAP121 to forms a PTPD1-Src-AKAP121 complex, which is required for efficient maintenance of mitochondrial membrane potential and ATP oxidative synthesis. As a novel component of the endocytic pathway, PTPN21 supports EGF receptor stability and mitogenic signaling in bladder cancer cells. Moreover, PTPD1 regulates focal adhesion kinase (FAK) autophosphorylation and cell migration through modulating Src-FAK signaling at adhesion sites.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 221379142  61 RVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQV-KIGPPYTFRLKVKFY 138
Cdd:cd17192    7 RIQLLNNEFVEFTLSVESTGQECLEAVAQRLELREITYFSLWYYNKQNQQRWVDLEKPLKKQLdKYALEPTVYFGVVFY 85

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142  58 IDCRVILLDnTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQ-VKIGPPYTFRLKVK 136
Cdd:cd17238    1 INVRVTTMD-AELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTQQdVKKENPLQFKFRAK 79

                 ..
gi 221379142 137 FY 138
Cdd:cd17238   80 FF 81

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 14 (PTPN14) and similar proteins; PTPN14, also termed protein-tyrosine phosphatase pez, or PTPD2, or PTP36, is a widely expressed non-transmembrane cytosolic protein tyrosine phosphatase (PTP). It belongs to the FERM family of PTPs characterized by a conserved N-terminal FERM domain and a C-terminal PTP catalytic domain with an intervening sequence containing an acidic region and a putative SH3 domain-binding sequence. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PTPN14 plays a role in the nucleus during cell proliferation. It forms a complex with Kibra and LATS1 proteins and negatively regulates the key Hippo pathway protein Yes-associated protein (YAP) oncogenic function by controlling its localization. It specifically regulates p130 Crk-associated substrate (p130Cas) phosphorylation at tyrosine residue 128 (Y128) in colorectal cancer (CRC) cells. Moreover, PTPN14 may be a critical enzyme in regulating endothelial cell function. It plays a crucial role in organogenesis by inducing transforming growth factor beta (TGFbeta) and epithelial-mesenchymal transition (EMT). It also acts as a modifier of angiogenesis and hereditary haemorrhagic telangiectasia. It regulates the lymphatic function and choanal development through the interaction with the vascular endothelial growth factor receptor 3 (VEGFR3), a receptor tyrosine kinase essential for lymphangiogenesis. Furthermore, PTPN14 functions as a regulator of cell motility through its action on cell-cell adhesion. Beta-Catenin, a central component of adherens junctions, has been identified as a PTPN14 substrate. PTPN14 works as a novel sperm-motility biomarker and a potential mitochondrial protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221379142  55 KNKIDCRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLDPTKPIKKQV-KIGPPYTFRL 133
Cdd:cd17191    1 KNCFVTRIRLLDSNVIECTLSVESTGQECLEAVAQRLELRETHYFGLWFLSKSQQARWVELEKPLKKQLdKFANEPLLFF 80

                 ....*
gi 221379142 134 KVKFY 138
Cdd:cd17191   81 GVMFY 85

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 221379142 244 MYGVDMHTVLGKDGCEYHLGLTPTGILVFERDQK----IGlFFWPKISKLDFKKKKLTLIVIEdddegrEQEHTFVFRLY 319
Cdd:cd13194    1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKltpkIG-FPWSEIRNISFNDKKFVIKPID------KKAPDFVFYSP 73

                         90       100
                 ....*....|....*....|...
gi 221379142 320 NEKACKH-LWKCAVEHHTFFRLR 341
Cdd:cd13194   74 RLRINKRiLDLCMGNHELYMRRR 96

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 4B (FRMD4B); 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). FRMD4B contains a FERM protein interaction domain as well as two coiled coil domains and may therefore function as a scaffolding protein. 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 221379142  60 CRVILLDNTDLSIELSKKALGSFLYEQVFYALDIIEKDYFGLQFMDANHVKHWLD----------PTKPikkqvkigPPY 129
Cdd:cd17200    5 CQVHLLDDRKLELLVQPKLLSRELLDLVASHFNLKEKEYFGITFIDDTGQSNWLQldhrvldhdlPKKS--------GPV 76

                 ....*....
gi 221379142 130 TFRLKVKFY 138
Cdd:cd17200   77 TLYFAVRFY 85

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor 13 (PTPH13); There are many functions of PTPN13 (also called PTPL1, PTP-BAS, hPTP1E, FAP1, or PTPL1). Mice lacking PTPN13 activity have abnormal regulation of signal transducer and activator of transcription signaling in their T cells, mild impairment of motor nerve repair, and a significant reduction in the growth of retinal glia cultures. It also plays a role in adipocyte differentiation. PTPN13 contains a kinase non-catalytic C-lobe domain (KIND), a FERM domain with two potential phosphatidylinositol 4,5-biphosphate [PtdIns(4,5)P2]-binding motifs, 5 PDZ domains, and a carboxy-terminal catalytic domain. There is an nteraction between the FERM domain of PTPL1 and PtdIns(4,5)P2 which is thought to regulate the membrane localization of PTPN13. PDZ are protein/protein interaction domains so there is the potential for numerous partners that can actively participate in the regulation of its phosphatase activity or can permit direct or indirect recruitment of tyrosine phosphorylated PTPL1 substrates. 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 221379142 262 LGLTPTGILVFE--RDQKIGL--FFWPKISKLDFKKKKLTLIVIEDDdegrEQEHTFVFRLYneKACKHLWK-CAVEHHT 336
Cdd:cd13187   20 LGICSRGIIIYEekNGARTPVlrFPWRETQKISFDKKKFTIESRGGS----GIKHTFYTDSY--KKSQYLLQlCSAQHKF 93

                 ....*.
gi 221379142 337 FFRLRA 342
Cdd:cd13187   94 HIQMRS 99

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 221379142 262 LGLTPTGILVFE----RDQKIGLFFWPKISKLDFKKKKLTlivIEDDDEGREqehtfvFRLY--NEKACKHLWK-CAVEH 334
Cdd:cd13185   23 LGITAKGIQIYQesdgEQQLLRTFPWSNIGKLSFDRKKFE---IRPEGSLRK------LTYYtsSDEKSKYLLAlCRETH 93