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 170932510  53 HRDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEGNEK 132
Cdd:cd17197    1 HRSICVLLPNKEQLSLTVGVKATGQELFQQVCELLKIKEAHFFGLSVVKNNEHIFMDLEQKLSKYFPKEWKKETGKGTEK 80

                         90
                 ....*....|....*...
gi 170932510 133 PRAPFVAFLRVQHYVENG 150
Cdd:cd17197   81 FSIPFVACFRVQYYVENG 98

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170932510 257 EDVPVHFFRLHKDKKEGRPTVILGLALRGVHIYQ-----------------------GKKLEIQLDGlpAAQKLVYYTGC 313
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQesdgeqqllrtfpwsnigklsfdRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 170932510 314 TWRSRHLLHLLRASHQLHLRVRPTLQQLR 342
Cdd:cd13185   79 DEKSKYLLALCRETHQFSMAIQPRLSEIR 107

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 170932510  53 HRDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEGNEK 132
Cdd:cd17197    1 HRSICVLLPNKEQLSLTVGVKATGQELFQQVCELLKIKEAHFFGLSVVKNNEHIFMDLEQKLSKYFPKEWKKETGKGTEK 80

                         90
                 ....*....|....*...
gi 170932510 133 PRAPFVAFLRVQHYVENG 150
Cdd:cd17197   81 FSIPFVACFRVQYYVENG 98

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 170932510 257 EDVPVHFFRLHKDKKEGRPTVILGLALRGVHIYQ-----------------------GKKLEIQLDGlpAAQKLVYYTGC 313
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQesdgeqqllrtfpwsnigklsfdRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 170932510 314 TWRSRHLLHLLRASHQLHLRVRPTLQQLR 342
Cdd:cd13185   79 DEKSKYLLALCRETHQFSMAIQPRLSEIR 107

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 170932510 158 ARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPHSYFPQWIITKRGIDYILRHMPTLHRER 237
Cdd:cd14473    1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKPEEWEKRIVELHKKL 80

                         90
                 ....*....|....*....
gi 170932510 238 QGLSPKEAMLCFIQEACRL 256
Cdd:cd14473   81 RGLSPAEAKLKYLKIARKL 99

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170932510  269 DKKEGrpTVILGLALRGVHIYQ--------------------GKKLEIQLDGLPAAQKLVYYTGCTWRSRHLLHLLRASH 328
Cdd:pfam09380   1 DKEGT--DLWLGVSAKGILVYEdnnkilnlfpwreirkisfkRKKFLIKLRDKSSEETLGFYTESSRACKYLWKLCVEQH 78

                  ....*..
gi 170932510  329 QLHLRVR 335
Cdd:pfam09380  79 TFFRLRR 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 170932510  53 HRDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEGNEK 132
Cdd:cd17197    1 HRSICVLLPNKEQLSLTVGVKATGQELFQQVCELLKIKEAHFFGLSVVKNNEHIFMDLEQKLSKYFPKEWKKETGKGTEK 80

                         90
                 ....*....|....*...
gi 170932510 133 PRAPFVAFLRVQHYVENG 150
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 170932510  148 ENGRVISDHRARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPHSYFPQWIITKRGIDYIL 227
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRKMKSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 170932510  228 RHMPTLHRERQGLSPKEAMLCFIQEACRLEDVPVHFF 264
Cdd:pfam00373  81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

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 170932510 257 EDVPVHFFRLHKDKKEGRPTVILGLALRGVHIYQ-----------------------GKKLEIQLDGlpAAQKLVYYTGC 313
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQesdgeqqllrtfpwsnigklsfdRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 170932510 314 TWRSRHLLHLLRASHQLHLRVRPTLQQLR 342
Cdd:cd13185   79 DEKSKYLLALCRETHQFSMAIQPRLSEIR 107

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 170932510 158 ARHLYYCHLKERVLRSQCAHREEAYFLLAACALQADLGEHRESAHAGRYFEPHSYFPQWIITKRGIDYILRHMPTLHRER 237
Cdd:cd14473    1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKPEEWEKRIVELHKKL 80

                         90
                 ....*....|....*....
gi 170932510 238 QGLSPKEAMLCFIQEACRL 256
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 170932510  54 RDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRN-NEYIFMDLEQKLSKYFSKdwkkernegnek 132
Cdd:cd01765    1 ISCRVRLLDGTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEDNdGQKHWLDLDKKISKQLKR------------ 68

                         90
                 ....*....|...
gi 170932510 133 pRAPFVAFLRVQH 145
Cdd:cd01765   69 -SGPYQFYFRVKF 80

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 170932510  54 RDVLVLLPSREQLRLAVGVKATGRELFQQVCNVASIRDAQFFGLCVVRNNEYIFMDLEQKLSKYFSKDWKKERNEgnEKP 133
Cdd:cd17196    2 RELNVIMPNGQCLEVKCDIKSRVRDVFNMVVAFANLVEHFYFGLAYMKGKEFFFLDHETKLHKVAPEGWKDQSKK--KTS 79

                         90
                 ....*....|....*.
gi 170932510 134 RAPFVAFLRVQHYVEN 149
Cdd:cd17196   80 IVNFTLFLRIKFFVDN 95

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170932510  269 DKKEGrpTVILGLALRGVHIYQ--------------------GKKLEIQLDGLPAAQKLVYYTGCTWRSRHLLHLLRASH 328
Cdd:pfam09380   1 DKEGT--DLWLGVSAKGILVYEdnnkilnlfpwreirkisfkRKKFLIKLRDKSSEETLGFYTESSRACKYLWKLCVEQH 78

                  ....*..
gi 170932510  329 QLHLRVR 335
Cdd:pfam09380  79 TFFRLRR 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 170932510 261 VHFFRLHKDKKEGRPTVILGLALRGVHIYQ-----------------------GKKLEIQLDGlPAAQKLVYYTGCTWRS 317
Cdd:cd13187    2 VHFHRVYREKKSSTLSLWLGICSRGIIIYEekngartpvlrfpwretqkisfdKKKFTIESRG-GSGIKHTFYTDSYKKS 80

                         90
                 ....*....|....*...
gi 170932510 318 RHLLHLLRASHQLHLRVR 335
Cdd:cd13187   81 QYLLQLCSAQHKFHIQMR 98

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 170932510  70 VGVKATGRELFQQVCNVASIRDAQFFGL-CVVRNNEYIFMDLEQKLSKYFSK 120
Cdd:cd17099   20 LSPESTGQDCLEYVAQRLELREIEYFGLrYVNKKGQLRWVDLEKPLKKQLDK 71

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 170932510 261 VHFFRLHKDKKEGRPtVILGLALRGVHIYQ----------------------GKKLEIQLDGLPAAQKLVYYTGCTwRSR 318
Cdd:cd00836    2 VEFFPVKDKSKKGSP-IILGVNPEGISVYDeltgqplvlfpwpnikkisfsgAKKFTIVVADEDKQSKLLFQTPSR-QAK 79

                         90
                 ....*....|..
gi 170932510 319 HLLHLLRASHQL 330
Cdd:cd00836   80 EIWKLIVGYHRF 91