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 767943605 210 EDVPVHFFRLHKDKKEGRPTVILGLALRGVHIYQEVDRAPQLLYDLPWPHVGKLAFLGKKLEIQLDGlpAAQKLVYYTGC 289
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 767943605 290 TWRSRHLLHLLRASHQLHLRVRPTLQQLR 318
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 767943605 210 EDVPVHFFRLHKDKKEGRPTVILGLALRGVHIYQEVDRAPQLLYDLPWPHVGKLAFLGKKLEIQLDGlpAAQKLVYYTGC 289
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 767943605 290 TWRSRHLLHLLRASHQLHLRVRPTLQQLR 318
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 767943605    23 SQVKATGRELFQQVCNVASIRDAQFFGLCVVR--NNEYIFMDLEQKLSKYFSKdwkkernegnekpRAPFVAFLRVQHYV 100
Cdd:smart00295  16 VDSSTTAEELLETVCRKLGIRESEYFGLQFEDpdEDLRHWLDPAKTLLDQDVK-------------SEPLTLYFRVKFYP 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943605   101 EN-GRVISDHRARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPH-SYFPQWIITKRGIDY 178
Cdd:smart00295  83 PDpNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGELSLkRFLPKQLLDSRKLKE 162

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 767943605   179 ILRHMPTLHRERQGLSPKEAMLCFIQEACRLEDVPVHFF 217
Cdd:smart00295 163 WRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943605  222 DKKEGrpTVILGLALRGVHIYQEVDRapqLLYDLPWPHVGKLAFLGKKLEIQLDGLPAAQKLVYYTGCTWRSRHLLHLLR 301
Cdd:pfam09380   1 DKEGT--DLWLGVSAKGILVYEDNNK---ILNLFPWREIRKISFKRKKFLIKLRDKSSEETLGFYTESSRACKYLWKLCV 75

                          90
                  ....*....|
gi 767943605  302 ASHQLHLRVR 311
Cdd:pfam09380  76 EQHTFFRLRR 85

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 767943605 210 EDVPVHFFRLHKDKKEGRPTVILGLALRGVHIYQEVDRAPQLLYDLPWPHVGKLAFLGKKLEIQLDGlpAAQKLVYYTGC 289
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 767943605 290 TWRSRHLLHLLRASHQLHLRVRPTLQQLR 318
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 767943605  101 ENGRVISDHRARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPHSYFPQWIITKRGIDYIL 180
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRKMKSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 767943605  181 RHMPTLHRERQGLSPKEAMLCFIQEACRLEDVPVHFF 217
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 767943605    23 SQVKATGRELFQQVCNVASIRDAQFFGLCVVR--NNEYIFMDLEQKLSKYFSKdwkkernegnekpRAPFVAFLRVQHYV 100
Cdd:smart00295  16 VDSSTTAEELLETVCRKLGIRESEYFGLQFEDpdEDLRHWLDPAKTLLDQDVK-------------SEPLTLYFRVKFYP 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943605   101 EN-GRVISDHRARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPH-SYFPQWIITKRGIDY 178
Cdd:smart00295  83 PDpNQLKEDPTRLNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGELSLkRFLPKQLLDSRKLKE 162

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 767943605   179 ILRHMPTLHRERQGLSPKEAMLCFIQEACRLEDVPVHFF 217
Cdd:smart00295 163 WRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943605  222 DKKEGrpTVILGLALRGVHIYQEVDRapqLLYDLPWPHVGKLAFLGKKLEIQLDGLPAAQKLVYYTGCTWRSRHLLHLLR 301
Cdd:pfam09380   1 DKEGT--DLWLGVSAKGILVYEDNNK---ILNLFPWREIRKISFKRKKFLIKLRDKSSEETLGFYTESSRACKYLWKLCV 75

                          90
                  ....*....|
gi 767943605  302 ASHQLHLRVR 311
Cdd:pfam09380  76 EQHTFFRLRR 85

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 767943605 214 VHFFRLHKDKKEGRPtVILGLALRGVHIYQEVDRapQLLYDLPWPHVGKLAF-LGKKLEIQLDGLPAAQKLVYYTGCTwR 292
Cdd:cd00836    2 VEFFPVKDKSKKGSP-IILGVNPEGISVYDELTG--QPLVLFPWPNIKKISFsGAKKFTIVVADEDKQSKLLFQTPSR-Q 77

                         90
                 ....*....|....
gi 767943605 293 SRHLLHLLRASHQL 306
Cdd:cd00836   78 AKEIWKLIVGYHRF 91

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767943605  24 QVKATGRELFQQVCNVASIRDAQFFGLCVVRN-NEYIFMDLEQKLSKYFSKdwkkernegnekpRAPFVAFLRVQH 98
Cdd:cd01765   18 SKKATGQELFDKVCEKLNLLEKDYFGLFYEDNdGQKHWLDLDKKISKQLKR-------------SGPYQFYFRVKF 80

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins; The ezrin-radixin-moesin (ERM) family includes a group of closely related cytoskeletal proteins that play an essential role in microvilli formation, T-cell activation, and tumor metastasis through providing a regulated linkage between F-actin and membrane-associated proteins. These proteins may also function in signaling cascades that regulate the assembly of actin stress fibers. The ERM proteins consist of an N-terminal FERM domain, a coiled-coil (CC) domain and a C-terminal tail segment (C-tail) containing a well-defined actin-binding motif. They exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Merlin, which is highly related to the members of the ezrin, radixin, and moesin (ERM) protein family that are directly attached to and functionally linked with NHE1, is included in this family.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767943605  24 QVKATGRELFQQVCNVASIRDAQFFGLC-VVRNNEYIFMDLEQKLSkyfskdwKKERNEGNekpraPFVAFLRVQHYVE 101
Cdd:cd17097   17 KPKAKGRELFDLVCRTIGLRETWYFGLQyENKKGRVAWLKPDKKVL-------TQDVSKNN-----TLKFFFLVKFYPE 83

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 767943605 221 KDKKeGRPtVILGLALRGVHIYQEVDR-APQLLYdlPWPHVGKLAFLGKKLEIQLDGLpAAQKLVYYTGCTWRSRHLLHL 299
Cdd:cd13194   10 KNKK-GTD-LWLGVDALGLNIYEPDNKlTPKIGF--PWSEIRNISFNDKKFVIKPIDK-KAPDFVFYSPRLRINKRILDL 84

                         90
                 ....*....|..
gi 767943605 300 LRASHQLHLRVR 311
Cdd:cd13194   85 CMGNHELYMRRR 96

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767943605  24 QVKATGRELFQQVCNVASIRDAQFFGL-CVVRNNEYIFMDLEQKLSKYFSK 73
Cdd:cd17099   21 SPESTGQDCLEYVAQRLELREIEYFGLrYVNKKGQLRWVDLEKPLKKQLDK 71

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in merlin and similar proteins; Merlin, also termed moesin-ezrin-radixin-like protein, or neurofibromin-2 (NF2), or Schwannomerlin, or Schwannomin, 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, merlin however lacks the typical actin-binding motif in the C-tail. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Merlin plays vital roles in controlling proper development of organ sizes by specifically binding to a large number of target proteins localized both in cytoplasm and nuclei. Merlin may function as a tumor suppressor that functions upstream of the core Hippo pathway kinases Lats1/2 (Wts in Drosophila) and Mst1/2 (Hpo in Drosophila), as well as the nuclear E3 ubiquitin ligase DDB1-and-Cullin 4-associated Factor 1 (DCAF1)-associated cullin 4-Roc1 ligase, CRL4(DCAF1). Merlin may also has a tumor suppressor function in melanoma cells, the inhibition of the proto-oncogenic Na(+)/H(+) exchanger isoform 1 (NHE1) activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767943605  24 QVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIF---MD---LEQKLSK 69
Cdd:cd17186   19 EMKWKGKDLFDLVCRTIGLRETWYFGLQYTDSKGTVAwlkMDkkvLDQDVPK 70