FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 1 (FRMD1); FRMD1 is an uncharacterized FERM domain-containing 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 767943601  33 HRDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEGNEK 112
Cdd:cd17197    1 HRSICVLLPNKEQLSLTVGVKATGQELFQQVCELLKIKEAHFFGLSVVKNNEHIFMDLEQKLSKYFPKEWKKETGKGTEK 80

                         90
                 ....*....|....*...
gi 767943601 113 PRAPFVAFLRVQHYVENG 130
Cdd:cd17197   81 FSIPFVACFRVQYYVENG 98

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943601  128 ENGRVISDHRARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPHSYFPQWIITKRGIDYIL 207
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRKMKSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 767943601  208 RHMPTLHRERQGLSPKEAMLCFIQEACRLEDVPVHFF 244
Cdd:pfam00373  81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 1 (FRMD1); FRMD1 is an uncharacterized FERM domain-containing 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 767943601  33 HRDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEGNEK 112
Cdd:cd17197    1 HRSICVLLPNKEQLSLTVGVKATGQELFQQVCELLKIKEAHFFGLSVVKNNEHIFMDLEQKLSKYFPKEWKKETGKGTEK 80

                         90
                 ....*....|....*...
gi 767943601 113 PRAPFVAFLRVQHYVENG 130
Cdd:cd17197   81 FSIPFVACFRVQYYVENG 98

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943601  128 ENGRVISDHRARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPHSYFPQWIITKRGIDYIL 207
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRKMKSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 767943601  208 RHMPTLHRERQGLSPKEAMLCFIQEACRLEDVPVHFF 244
Cdd:pfam00373  81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

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 767943601 138 ARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPHSYFPQWIITKRGIDYILRHMPTLHRER 217
Cdd:cd14473    1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKPEEWEKRIVELHKKL 80

                         90
                 ....*....|....*....
gi 767943601 218 QGLSPKEAMLCFIQEACRL 236
Cdd:cd14473   81 RGLSPAEAKLKYLKIARKL 99

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943601  249 DKKEGrpTVILGLALRGVHIYQEVDRapqLLYDLPWPHVGKLAFLGKKLEIQLDGLPAAQKLVYYTGCTWRSRHLLHLLR 328
Cdd:pfam09380   1 DKEGT--DLWLGVSAKGILVYEDNNK---ILNLFPWREIRKISFKRKKFLIKLRDKSSEETLGFYTESSRACKYLWKLCV 75

                          90
                  ....*....|
gi 767943601  329 ASHQLHLRVR 338
Cdd:pfam09380  76 EQHTFFRLRR 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 1 (FRMD1); FRMD1 is an uncharacterized FERM domain-containing 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 767943601  33 HRDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEGNEK 112
Cdd:cd17197    1 HRSICVLLPNKEQLSLTVGVKATGQELFQQVCELLKIKEAHFFGLSVVKNNEHIFMDLEQKLSKYFPKEWKKETGKGTEK 80

                         90
                 ....*....|....*...
gi 767943601 113 PRAPFVAFLRVQHYVENG 130
Cdd:cd17197   81 FSIPFVACFRVQYYVENG 98

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 13 (PTPN13) and similar proteins; This family includes tyrosine-protein phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and FERM domain-containing proteins FRMD1 and FRMD6. All family members contain a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943601  33 HRDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEGNEK 112
Cdd:cd17101    1 RRYVNVVLLNGQRLQVAVDVKTTVQDLFDQVCDHLGLQETELFGLAVLKDGEYFFLDPDTKLSKYAPKGWKSEAKKGLKG 80

                         90
                 ....*....|....*..
gi 767943601 113 PRAPFVAFLRVQHYVEN 129
Cdd:cd17101   81 GKPVFTLYFRVKFYVDN 97

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 6 (FRMD6); FRMD6, also termed willin, expanded or expanded homolog, is a FERM domain-containing protein that plays a critical role in regulating both cell proliferation and apoptosis. It acts as a tumor suppressor of human breast cancer cells independently of the Hippo pathway. It also inhibits human glioblastoma growth and progression by negatively regulating activity of receptor tyrosine kinases. As an upstream component of the hippo signaling pathway, FRMD6 orchestrates mammalian peripheral nerve fibroblasts. FRMD6 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 767943601  34 RDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEGNEKP 113
Cdd:cd17198    2 RSVCVFLPNDETLNIIVNVKTLCQELLVQVCDLLRLKDCHLFGLSVIQNNEHVYMELSQKLYKYCPKEWKKEASKGIDQF 81

                         90
                 ....*....|....*..
gi 767943601 114 RAPFVAFLRVQHYVENG 130
Cdd:cd17198   82 GPPMIVHFRVQYYVENG 98

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 767943601 138 ARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPHSYFPQWIITKRGIDYILRHMPTLHRER 217
Cdd:cd14473    1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKPEEWEKRIVELHKKL 80

                         90
                 ....*....|....*....
gi 767943601 218 QGLSPKEAMLCFIQEACRL 236
Cdd:cd14473   81 RGLSPAEAKLKYLKIARKL 99

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943601  249 DKKEGrpTVILGLALRGVHIYQEVDRapqLLYDLPWPHVGKLAFLGKKLEIQLDGLPAAQKLVYYTGCTWRSRHLLHLLR 328
Cdd:pfam09380   1 DKEGT--DLWLGVSAKGILVYEDNNK---ILNLFPWREIRKISFKRKKFLIKLRDKSSEETLGFYTESSRACKYLWKLCV 75

                          90
                  ....*....|
gi 767943601  329 ASHQLHLRVR 338
Cdd:pfam09380  76 EQHTFFRLRR 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 767943601 241 VHFFRLHKDKKEGRPTVILGLALRGVHIYQEVDRAPQLLYDLPWPHVGKLAFLGKKLEIQLDGlPAAQKLVYYTGCTWRS 320
Cdd:cd13187    2 VHFHRVYREKKSSTLSLWLGICSRGIIIYEEKNGARTPVLRFPWRETQKISFDKKKFTIESRG-GSGIKHTFYTDSYKKS 80

                         90
                 ....*....|....*...
gi 767943601 321 RHLLHLLRASHQLHLRVR 338
Cdd:cd13187   81 QYLLQLCSAQHKFHIQMR 98

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 13 (PTPN13); PTPN13, also termed Fas-associated protein-tyrosine phosphatase 1 (FAP-1), or PTP-BAS, or protein-tyrosine phosphatase 1E (PTP-E1 or PTPE1), or protein-tyrosine phosphatase PTPL1, belongs to the non-transmembrane FERM-containing protein-tyrosine phosphatase (PTP) subfamily characterized by a KIND domain, a FERM domain, five PDZ domains, 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). PTPN13 interacts with a variety of ligands, suggests an important role as a scaffolding protein. It is also involved in the regulation of apoptosis, cytokinesis and cell cycle progression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943601  34 RDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEGNeKP 113
Cdd:cd17195    2 RKVNIMLLSGQRLELTCDTKSTCKDVFDMVVAHIGLVEHHLFALAYLKDNEFFFVDPDLKLSKVAPEGWKEEPKKKN-KM 80

                         90
                 ....*....|....*.
gi 767943601 114 RAPFVAFLRVQHYVEN 129
Cdd:cd17195   81 TVNFTLFFRIKFFVDD 96

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943601  44 EQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLC-VVRNNEYIFMDLEQKLSkyfskdwKKERNEGNekpraPFVAFLR 122
Cdd:cd17097   10 AELEFSIKPKAKGRELFDLVCRTIGLRETWYFGLQyENKKGRVAWLKPDKKVL-------TQDVSKNN-----TLKFFFL 77

                 ....*.
gi 767943601 123 VQHYVE 128
Cdd:cd17097   78 VKFYPE 83

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins, Ezrin, Radixin, and Moesin; The ezrin-radixin-moesin (ERM) family includes a group of closely related 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. 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).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767943601  45 QLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYI-FMDLEQKLSkyfSKDWKKE 105
Cdd:cd17187   11 ELEFAIQPNTTGKQLFDQVVKTIGLREIWFFGLQYVDSKGYStWLKLNKKVL---SQDVKKE 69

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 767943601  45 QLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEY-IFMDLEQKLSKyfsKDWKKErNEGNEKPRAPF 117
Cdd:cd17238   11 ELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYsTWLKLNKKVTQ---QDVKKE-NPLQFKFRAKF 80

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 767943601  45 QLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIF---MD---LEQKLSK 96
Cdd:cd17186   13 EMEFNCEMKWKGKDLFDLVCRTIGLRETWYFGLQYTDSKGTVAwlkMDkkvLDQDVPK 70