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 162287308 215 EDVPVTFYRLQKDKKEEKGSALLGLTLRGMQVFQEVNNVRDLLYDFPWFHVGRLTFLGKKFEIQPDGlpSARKLVYYTGS 294
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 162287308 295 AFRSRHLLLHLSSCHRLYLSLQPALKHLR 323
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 162287308 215 EDVPVTFYRLQKDKKEEKGSALLGLTLRGMQVFQEVNNVRDLLYDFPWFHVGRLTFLGKKFEIQPDGlpSARKLVYYTGS 294
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 162287308 295 AFRSRHLLLHLSSCHRLYLSLQPALKHLR 323
Cdd:cd13185   79 DEKSKYLLALCRETHQFSMAIQPRLSEIR 107

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287308  229 KEEKGSALLGLTLRGMQVFQEVNNVRdllYDFPWFHVGRLTFLGKKFEIQPDGLPSARKLVYYTGSAFRSRHLLLHLSSC 308
Cdd:pfam09380   1 DKEGTDLWLGVSAKGILVYEDNNKIL---NLFPWREIRKISFKRKKFLIKLRDKSSEETLGFYTESSRACKYLWKLCVEQ 77

                  ....*...
gi 162287308  309 HRLYLSLQ 316
Cdd:pfam09380  78 HTFFRLRR 85

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 162287308   13 VLLPNKETLDITVGVKATGQDVFHRVCELLGVRELHYFGLTLVKNN-EHIFLDLEEKLAKYFP 74
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 162287308 215 EDVPVTFYRLQKDKKEEKGSALLGLTLRGMQVFQEVNNVRDLLYDFPWFHVGRLTFLGKKFEIQPDGlpSARKLVYYTGS 294
Cdd:cd13185    1 EDLNAHLYRLRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEG--SLRKLTYYTSS 78

                         90       100
                 ....*....|....*....|....*....
gi 162287308 295 AFRSRHLLLHLSSCHRLYLSLQPALKHLR 323
Cdd:cd13185   79 DEKSKYLLALCRETHQFSMAIQPRLSEIR 107

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 162287308   9 RTVCVLLPNKETLDITVGVKATGQDVFHRVCELLGVRELHYFGLTLVKNNEHIFLDLEEKLAKYFPKEWKQDSGKGSHRR 88
Cdd:cd17198    2 RSVCVFLPNDETLNIIVNVKTLCQELLVQVCDLLRLKDCHLFGLSVIQNNEHVYMELSQKLYKYCPKEWKKEASKGIDQF 81

                         90
                 ....*....|....*..
gi 162287308  89 SIPPLLCLKVQYYVENG 105
Cdd:cd17198   82 GPPMIVHFRVQYYVENG 98

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287308  229 KEEKGSALLGLTLRGMQVFQEVNNVRdllYDFPWFHVGRLTFLGKKFEIQPDGLPSARKLVYYTGSAFRSRHLLLHLSSC 308
Cdd:pfam09380   1 DKEGTDLWLGVSAKGILVYEDNNKIL---NLFPWREIRKISFKRKKFLIKLRDKSSEETLGFYTESSRACKYLWKLCVEQ 77

                  ....*...
gi 162287308  309 HRLYLSLQ 316
Cdd:pfam09380  78 HTFFRLRR 85

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 162287308   13 VLLPNKETLDITVGVKATGQDVFHRVCELLGVRELHYFGLTLVKNN-EHIFLDLEEKLAKYFP 74
Cdd:pfam09379   1 VRLLDGTVLEFDVQPKATGQVLLDQVCNHLNLKEKDYFGLQFLDDNgEHRWLDLSKRLSKQAP 63

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 162287308   9 RTVCVLLPNKETLDITVGVKATGQDVFHRVCELLGVRELHYFGLTLVKNNEHIFLDLEEKLAKYFPKEWKQDSgKGSHRR 88
Cdd:cd17195    2 RKVNIMLLSGQRLELTCDTKSTCKDVFDMVVAHIGLVEHHLFALAYLKDNEFFFVDPDLKLSKVAPEGWKEEP-KKKNKM 80

                         90
                 ....*....|....*.
gi 162287308  89 SIPPLLCLKVQYYVEN 104
Cdd:cd17195   81 TVNFTLFFRIKFFVDD 96

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 162287308  13 VLLPNKETLDITVGVKATGQDVFHRVCELLGVRELHYFGLTLV-KNNEHIFLDLEEKLAKYFPK 75
Cdd:cd01765    5 VRLLDGTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEdNDGQKHWLDLDKKISKQLKR 68

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 162287308 113 ARKLYYYDLRERVLRSECRQQEEVYFQLAGFALQADHSDHSSEGQSHGhamYFQPKEYFPPWIIAKRGIDYLLCHGPKVH 192
Cdd:cd14473    1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPK---YLSLKRFLPKQLLKQRKPEEWEKRIVELH 77

                         90       100
                 ....*....|....*....|..
gi 162287308 193 KELWGMSCRDAVLLFIRESCRL 214
Cdd:cd14473   78 KKLRGLSPAEAKLKYLKIARKL 99

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 162287308 219 VTFYRLqKDKKEEKGSALLGLTLRGMQVFQevNNVRDLLYDFPWFHVGRLTF-LGKKFEIQPDGLPSARKLVYYTGSAfR 297
Cdd:cd00836    2 VEFFPV-KDKSKKGSPIILGVNPEGISVYD--ELTGQPLVLFPWPNIKKISFsGAKKFTIVVADEDKQSKLLFQTPSR-Q 77

                         90
                 ....*....|....*.
gi 162287308 298 SRHLLLHLSSCHRLYL 313
Cdd:cd00836   78 AKEIWKLIVGYHRFLL 93

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 21 (PTPN21) and similar proteins; PTPN21, also termed protein-tyrosine phosphatase D1 (PTPD1), is a cytosolic non-receptor protein-tyrosine phosphatase (PTP) that belongs 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). 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. It also associates with and activates Src tyrosine kinase, and directs epidermal growth factor (EGF)/Src signaling to the nucleus through activating ERK1/2- and Elk1-dependent gene transcription. PTPD1-Src complex interacts a protein kinase A-anchoring protein AKAP121 to forms a PTPD1-Src-AKAP121 complex, which is required for efficient maintenance of mitochondrial membrane potential and ATP oxidative synthesis. As a novel component of the endocytic pathway, PTPN21 supports EGF receptor stability and mitogenic signaling in bladder cancer cells. Moreover, PTPD1 regulates focal adhesion kinase (FAK) autophosphorylation and cell migration through modulating Src-FAK signaling at adhesion sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287308  15 LPNKETLDITVGVKATGQDVFHRVCELLGVRELHYFGLTLV-KNNEHIFLDLEEKLAKYFPKewkqdsgkgshrRSIPPL 93
Cdd:cd17192   10 LLNNEFVEFTLSVESTGQECLEAVAQRLELREITYFSLWYYnKQNQQRWVDLEKPLKKQLDK------------YALEPT 77

                 ....*....
gi 162287308  94 LCLKVQYYV 102
Cdd:cd17192   78 VYFGVVFYV 86

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 14 (PTPN14) and similar proteins; PTPN14, also termed protein-tyrosine phosphatase pez, or PTPD2, or PTP36, is a widely expressed non-transmembrane cytosolic protein tyrosine phosphatase (PTP). It belongs 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. It forms a complex with Kibra and LATS1 proteins and negatively regulates the key Hippo pathway protein Yes-associated protein (YAP) oncogenic function by controlling its localization. It specifically regulates p130 Crk-associated substrate (p130Cas) phosphorylation at tyrosine residue 128 (Y128) in colorectal cancer (CRC) cells. Moreover, PTPN14 may be a critical enzyme in regulating endothelial cell function. It plays a crucial role in organogenesis by inducing transforming growth factor beta (TGFbeta) and epithelial-mesenchymal transition (EMT). It also acts as a modifier of angiogenesis and hereditary haemorrhagic telangiectasia. It regulates the lymphatic function and choanal development through the interaction with the vascular endothelial growth factor receptor 3 (VEGFR3), a receptor tyrosine kinase essential for lymphangiogenesis. Furthermore, PTPN14 functions as a regulator of cell motility through its action on cell-cell adhesion. Beta-Catenin, a central component of adherens junctions, has been identified as a PTPN14 substrate. PTPN14 works as a novel sperm-motility biomarker and a potential mitochondrial protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 162287308  13 VLLPNKETLDITVGVKATGQDVFHRVCELLGVRELHYFGL-TLVKNNEHIFLDLEEKLAKYFPKEWKQdsgkgshrrsip 91
Cdd:cd17191    8 IRLLDSNVIECTLSVESTGQECLEAVAQRLELRETHYFGLwFLSKSQQARWVELEKPLKKQLDKFANE------------ 75

                         90
                 ....*....|.
gi 162287308  92 PLLCLKVQYYV 102
Cdd:cd17191   76 PLLFFGVMFYV 86

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 2 (EPB41L2) and similar proteins; EPB41L2, also termed generally expressed protein 4.1 (4.1G), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L2 contains a FERM domain, a spectrin and actin binding (SAB) domain, and a C-terminal 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).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 162287308  28 KATGQDVFHRVCELLGVRELHYFGLTLVKNNEHifldleeklakyfpKEWkQDSGKGSHR--RSIPPLLCLKVQYY 101
Cdd:cd17202   21 RAKGQVLFDKVCEHLNLLEKDYFGLLYQVSANQ--------------KNW-LDSTKEIKRqiRRLPWLFTFNVKFY 81