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 767943599 299 EDVPVHFFRLHKDKKEGRPTVILGLALRGVHIYQEVDRAPQLLYDLPWPHVGKLAFLGKKLEIQLDGlpAAQKLVYYTGC 378
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 767943599 379 TWRSRHLLHLLRASHQLHLRVRPTLQQLR 407
Cdd:cd13185   79 DEKSKYLLALCRETHQFSMAIQPRLSEIR 107

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 767943599 299 EDVPVHFFRLHKDKKEGRPTVILGLALRGVHIYQEVDRAPQLLYDLPWPHVGKLAFLGKKLEIQLDGlpAAQKLVYYTGC 378
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 767943599 379 TWRSRHLLHLLRASHQLHLRVRPTLQQLR 407
Cdd:cd13185   79 DEKSKYLLALCRETHQFSMAIQPRLSEIR 107

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 767943599    98 VLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVR--NNEYIFMDLEQKLSKYFSKdwkkernegnekp 175
Cdd:smart00295   2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDpdEDLRHWLDPAKTLLDQDVK------------- 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943599   176 RAPFVAFLRVQHYVEN-GRVISDHRARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPH-S 253
Cdd:smart00295  69 SEPLTLYFRVKFYPPDpNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGELSLkR 148

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 767943599   254 YFPQWIITKRGIDYILRHMPTLHRERQGLSPKEAMLCFIQEACRLEDVPVHFF 306
Cdd:smart00295 149 FLPKQLLDSRKLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

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 767943599  100 VLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNN-EYIFMDLEQKLSKYFS 161
Cdd:pfam09379   1 VRLLDGTVLEFDVQPKATGQVLLDQVCNHLNLKEKDYFGLQFLDDNgEHRWLDLSKRLSKQAP 63

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 767943599 299 EDVPVHFFRLHKDKKEGRPTVILGLALRGVHIYQEVDRAPQLLYDLPWPHVGKLAFLGKKLEIQLDGlpAAQKLVYYTGC 378
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 767943599 379 TWRSRHLLHLLRASHQLHLRVRPTLQQLR 407
Cdd:cd13185   79 DEKSKYLLALCRETHQFSMAIQPRLSEIR 107

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943599  190 ENGRVISDHRARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPHSYFPQWIITKRGIDYIL 269
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRKMKSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 767943599  270 RHMPTLHRERQGLSPKEAMLCFIQEACRLEDVPVHFF 306
Cdd:pfam00373  81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

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 767943599    98 VLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVR--NNEYIFMDLEQKLSKYFSKdwkkernegnekp 175
Cdd:smart00295   2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDpdEDLRHWLDPAKTLLDQDVK------------- 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943599   176 RAPFVAFLRVQHYVEN-GRVISDHRARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPH-S 253
Cdd:smart00295  69 SEPLTLYFRVKFYPPDpNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGELSLkR 148

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 767943599   254 YFPQWIITKRGIDYILRHMPTLHRERQGLSPKEAMLCFIQEACRLEDVPVHFF 306
Cdd:smart00295 149 FLPKQLLDSRKLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

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 767943599  100 VLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNN-EYIFMDLEQKLSKYFS 161
Cdd:pfam09379   1 VRLLDGTVLEFDVQPKATGQVLLDQVCNHLNLKEKDYFGLQFLDDNgEHRWLDLSKRLSKQAP 63

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 767943599  96 RDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRN-NEYIFMDLEQKLSKYFSKdwkkernegnek 174
Cdd:cd01765    1 ISCRVRLLDGTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEDNdGQKHWLDLDKKISKQLKR------------ 68

                         90
                 ....*....|...
gi 767943599 175 pRAPFVAFLRVQH 187
Cdd:cd01765   69 -SGPYQFYFRVKF 80

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 767943599 303 VHFFRLHKDKKEGRPTVILGLALRGVHIYQEVDRAPQLLYDLPWPHVGKLAFLGKKLEIQLDGlPAAQKLVYYTGCTWRS 382
Cdd:cd13187    2 VHFHRVYREKKSSTLSLWLGICSRGIIIYEEKNGARTPVLRFPWRETQKISFDKKKFTIESRG-GSGIKHTFYTDSYKKS 80

                         90
                 ....*....|....*...
gi 767943599 383 RHLLHLLRASHQLHLRVR 400
Cdd:cd13187   81 QYLLQLCSAQHKFHIQMR 98

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943599  96 RDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEgnEKP 175
Cdd:cd17196    2 RELNVIMPNGQCLEVKCDIKSRVRDVFNMVVAFANLVEHFYFGLAYMKGKEFFFLDHETKLHKVAPEGWKDQSKK--KTS 79

                         90
                 ....*....|....*.
gi 767943599 176 RAPFVAFLRVQHYVEN 191
Cdd:cd17196   80 IVNFTLFLRIKFFVDN 95

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767943599 107 QLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYI-FMDLEQKLSkyfSKDWKKErNEGNEKPRAPF 179
Cdd:cd17239   13 ELEFAIQPNTTGKQLFDQVVKTIGLREVWYFGLQYVDNKGFPtWLKLDKKVS---AQEVRKE-NPLQFKFRAKF 82

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 767943599 310 KDKKeGRPtVILGLALRGVHIYQEVDR-APQLLYdlPWPHVGKLAFLGKKLEIQLDGLpAAQKLVYYTGCTWRSRHLLHL 388
Cdd:cd13194   10 KNKK-GTD-LWLGVDALGLNIYEPDNKlTPKIGF--PWSEIRNISFNDKKFVIKPIDK-KAPDFVFYSPRLRINKRILDL 84

                         90
                 ....*....|..
gi 767943599 389 LRASHQLHLRVR 400
Cdd:cd13194   85 CMGNHELYMRRR 96

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 767943599 107 QLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEY-IFMDLEQKLSKyfsKDWKKErNEGNEKPRAPF 179
Cdd:cd17238   11 ELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYsTWLKLNKKVTQ---QDVKKE-NPLQFKFRAKF 80