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 2452621382  46 RYLLYLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDYDPDEHPENYINDFKIFPKQSQK------LEKKIAEMHKnDF 119
Cdd:cd14473     2 RYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKqrkpeeWEKRIVELHK-KL 80

                          90
                  ....*....|....*....
gi 2452621382 120 RGQSPAVAEFNLLLKAYSL 138
Cdd:cd14473    81 RGLSPAEAKLKYLKIARKL 99

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.

                          10
                  ....*....|....*.
gi 2452621382   1 MKSHPPYTMCFRVKFY 16
Cdd:cd17102    67 LKGVPPYVLCFRVKFY 82

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 2452621382  46 RYLLYLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDYDPDEHPENYINDFKIFPKQSQK------LEKKIAEMHKnDF 119
Cdd:cd14473     2 RYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKqrkpeeWEKRIVELHK-KL 80

                          90
                  ....*....|....*....
gi 2452621382 120 RGQSPAVAEFNLLLKAYSL 138
Cdd:cd14473    81 RGLSPAEAKLKYLKIARKL 99

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 2452621382    5 PPYTMCFRVKFYPHEPLKIKEELTSsyrgraalrgmggvhlRYLLYLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDY 84
Cdd:smart00295  70 EPLTLYFRVKFYPPDPNQLKEDPTR----------------LNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDY 133

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2452621382   85 DPDEHP-ENYINDFKIFPKQ------SQKLEKKIAEMHKNdFRGQSPAVAEFNLLLKAYSLETYGVDPH 146
Cdd:smart00295 134 DEELHDlRGELSLKRFLPKQlldsrkLKEWRERIVELHKE-LIGLSPEEAKLKYLELARKLPTYGVELF 201

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 2452621382 244 KIFFKGSRFRYSGKVAKEVVEASSKIQREPPEVHRTSITQSRSS 287
Cdd:pfam08736   1 KFFSLGSKFRYSGRTQKQTVEDSSEILRPQPEFERSPSKRYPSR 44

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 2452621382  46 RYLLYLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDYDPDEHPENYINDFKIFPKQSQK------LEKKIAEMHKnDF 119
Cdd:cd14473     2 RYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKqrkpeeWEKRIVELHK-KL 80

                          90
                  ....*....|....*....
gi 2452621382 120 RGQSPAVAEFNLLLKAYSL 138
Cdd:cd14473    81 RGLSPAEAKLKYLKIARKL 99

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 2452621382    5 PPYTMCFRVKFYPHEPLKIKEELTSsyrgraalrgmggvhlRYLLYLQIKRDIFHGRLLCSFSDAAYLGACIVQAELGDY 84
Cdd:smart00295  70 EPLTLYFRVKFYPPDPNQLKEDPTR----------------LNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDY 133

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2452621382   85 DPDEHP-ENYINDFKIFPKQ------SQKLEKKIAEMHKNdFRGQSPAVAEFNLLLKAYSLETYGVDPH 146
Cdd:smart00295 134 DEELHDlRGELSLKRFLPKQlldsrkLKEWRERIVELHKE-LIGLSPEEAKLKYLELARKLPTYGVELF 201

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 2452621382 244 KIFFKGSRFRYSGKVAKEVVEASSKIQREPPEVHRTSITQSRSS 287
Cdd:pfam08736   1 KFFSLGSKFRYSGRTQKQTVEDSSEILRPQPEFERSPSKRYPSR 44

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 3 and 4 (PTPN4 and PTPN3); PTPN4 (also called PTPMEG, protein tyrosine phosphatase, megakaryocyte) is a cytoplasmic protein-tyrosine phosphatase (PTP) thought to play a role in cerebellar function. PTPMEG-knockout mice have impaired memory formation and cerebellar long-term depression. PTPN3/PTPH1 is a membrane-associated PTP that is implicated in regulating tyrosine phosphorylation of growth factor receptors, p97 VCP (valosin-containing protein, or Cdc48 in Saccharomyces cerevisiae), and HBV (Hepatitis B Virus) gene expression; it is mutated in a subset of colon cancers. PTPMEG and PTPN3/PTPH1 contains a N-terminal FERM domain, a middle PDZ domain, and a C-terminal phosphatase domain. PTP1/Tyrosine-protein phosphatase 1 from nematodes and a FERM_C repeat 1 from Tetraodon nigroviridis are also included in this cd. 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 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 2452621382 140 TYGVDPHPCKDSTGTTTFLGFTAAGFVVFQGNKRIHLLKWCDVYKLKFEGKTFYVFGAQK---EKKAMLSFHTSTPAACK 216
Cdd:cd13189     1 LYGVELHSARDSNNLELQIGVSSAGILVFQNGIRINTFPWSKIVKISFKRKQFFIQLRREpneSRDTILGFNMLSYRACK 80

                          90
                  ....*....|....
gi 2452621382 217 HLWKCGVENQAFYK 230
Cdd:cd13189    81 NLWKSCVEHHTFFR 94

FERM domain C-lobe of FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FRMD7(FERM domain containing 7). FARP1 and FARP2 are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. These members are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. Other members in this family do not contain the DH domains such as the Human FERM domain containing protein 7 and Caenorhabditis elegans CFRM3, both of which have unknown functions. They contain an N-terminal FERM domain, a PH domain, followed by a FA (FERM adjacent) domain. 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 2452621382 135 AYSLETYGVDPHPCKDSTGTTTFLGFTAAGFVVFQGNKRIHLLKWCDVYKLKFEGKTFYV---FGAQKEKKAMLSFHTST 211
Cdd:cd13193     3 ARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFLIklhPEAYGSYKDTVEFSFES 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2452621382 212 PAACKHLWKCGVENQAFYKYAKSSQIKtMSSSKIFFKGSRF 252
Cdd:cd13193    83 RNECKSFWKKCIEHHAFFRCSEVPKPP-SPKLRLFSRGSSF 122

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
                  ....*....|....*.
gi 2452621382   1 MKSHPPYTMCFRVKFY 16
Cdd:cd17102    67 LKGVPPYVLCFRVKFY 82