kinase non-catalytic C-lobe domain; It is an interaction domain identified as being similar to the C-terminal protein kinase catalytic fold (C lobe). Its presence at the N terminus of signalling proteins and the absence of the active-site residues in the catalytic and activation loops suggest that it folds independently and is likely to be non-catalytic. The occurrence of KIND only in metazoa implies that it has evolved from the catalytic protein kinase domain into an interaction domain possibly by keeping the substrate-binding features

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462517218   13 VTLASALQVRGEALSEEEIWSLLFLAAEQLLEDLRNDSSDYVVCPWSALLSAAGSLSFQGRVSHIEAAPFKAPELLQGQS 92
Cdd:smart00750   1 VSLADILEVRGRPLNEEEIWAVCLQCLGALRELHRQAKSGNILLTWDGLLKLDGSVAFKTPEQSRPDPYFMAPEVIQGQS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462517218   93 EDEqpdasQMHVYSLGMTLYWSAGFHVPPHQPLQLCEPLHSILLTMCEDQPHRRCTLQSVLEACRvHEKEVSVYpAPAGL 172
Cdd:smart00750  81 YTE-----KADIYSLGITLYEALDYELPYNEERELSAILEILLNGMPADDPRDRSNLEGVSAARS-FEDFMRLC-ASRLP 153

                          170       180
                   ....*....|....*....|...
gi 2462517218  173 HIRRLVGLVLGTISEVEKRVVEE 195
Cdd:smart00750 154 QRREAANHYLAHCRALFAETLEL 176

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 2462517218 543 GVLVHQVFSEKRRPEEEMALGICAKGVIVYEVKNNSRIAMLRFQWRETGKISTYQKKFTITSSV-TGKKHTFVTDSAKTS 621
Cdd:cd13187     1 GVHFHRVYREKKSSTLSLWLGICSRGIIIYEEKNGARTPVLRFPWRETQKISFDKKKFTIESRGgSGIKHTFYTDSYKKS 80

                          90       100
                  ....*....|....*....|...
gi 2462517218 622 KYLLDLCSAQHGFNAQMGSGQPS 644
Cdd:cd13187    81 QYLLQLCSAQHKFHIQMRSRQST 103

kinase non-catalytic C-lobe domain; It is an interaction domain identified as being similar to the C-terminal protein kinase catalytic fold (C lobe). Its presence at the N terminus of signalling proteins and the absence of the active-site residues in the catalytic and activation loops suggest that it folds independently and is likely to be non-catalytic. The occurrence of KIND only in metazoa implies that it has evolved from the catalytic protein kinase domain into an interaction domain possibly by keeping the substrate-binding features

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462517218   13 VTLASALQVRGEALSEEEIWSLLFLAAEQLLEDLRNDSSDYVVCPWSALLSAAGSLSFQGRVSHIEAAPFKAPELLQGQS 92
Cdd:smart00750   1 VSLADILEVRGRPLNEEEIWAVCLQCLGALRELHRQAKSGNILLTWDGLLKLDGSVAFKTPEQSRPDPYFMAPEVIQGQS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462517218   93 EDEqpdasQMHVYSLGMTLYWSAGFHVPPHQPLQLCEPLHSILLTMCEDQPHRRCTLQSVLEACRvHEKEVSVYpAPAGL 172
Cdd:smart00750  81 YTE-----KADIYSLGITLYEALDYELPYNEERELSAILEILLNGMPADDPRDRSNLEGVSAARS-FEDFMRLC-ASRLP 153

                          170       180
                   ....*....|....*....|...
gi 2462517218  173 HIRRLVGLVLGTISEVEKRVVEE 195
Cdd:smart00750 154 QRREAANHYLAHCRALFAETLEL 176

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 2462517218 543 GVLVHQVFSEKRRPEEEMALGICAKGVIVYEVKNNSRIAMLRFQWRETGKISTYQKKFTITSSV-TGKKHTFVTDSAKTS 621
Cdd:cd13187     1 GVHFHRVYREKKSSTLSLWLGICSRGIIIYEEKNGARTPVLRFPWRETQKISFDKKKFTIESRGgSGIKHTFYTDSYKKS 80

                          90       100
                  ....*....|....*....|...
gi 2462517218 622 KYLLDLCSAQHGFNAQMGSGQPS 644
Cdd:cd13187    81 QYLLQLCSAQHKFHIQMRSRQST 103

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462517218 435 LLQHSLTRHQFYLQLRKDILEERLYCNEEILLQLGVLALQAEFGNYPKEVESKPYFHVEDYIPASLIERMTALRVQVEVS 514
Cdd:pfam00373   5 LLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLRKMKSKELEKRVL 84

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462517218 515 EMHRLSSALWGEDAELKFLRVTQQLPEYGVLVH 547
Cdd:pfam00373  85 EAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 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 2462517218 441 TRHQFYLQLRKDILEERLYCNEEILLQLGVLALQAEFGNYPKEVESKPYFHVEDYIPASLIERMTALRVQVEVSEMHRLS 520
Cdd:cd14473     1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKPEEWEKRIVELHKKL 80

                          90
                  ....*....|....*....
gi 2462517218 521 SALWGEDAELKFLRVTQQL 539
Cdd:cd14473    81 RGLSPAEAKLKYLKIARKL 99

kinase non-catalytic C-lobe domain; It is an interaction domain identified as being similar to the C-terminal protein kinase catalytic fold (C lobe). Its presence at the N terminus of signalling proteins and the absence of the active-site residues in the catalytic and activation loops suggest that it folds independently and is likely to be non-catalytic. The occurrence of KIND only in metazoa implies that it has evolved from the catalytic protein kinase domain into an interaction domain possibly by keeping the substrate-binding features

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462517218   13 VTLASALQVRGEALSEEEIWSLLFLAAEQLLEDLRNDSSDYVVCPWSALLSAAGSLSFQGRVSHIEAAPFKAPELLQGQS 92
Cdd:smart00750   1 VSLADILEVRGRPLNEEEIWAVCLQCLGALRELHRQAKSGNILLTWDGLLKLDGSVAFKTPEQSRPDPYFMAPEVIQGQS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462517218   93 EDEqpdasQMHVYSLGMTLYWSAGFHVPPHQPLQLCEPLHSILLTMCEDQPHRRCTLQSVLEACRvHEKEVSVYpAPAGL 172
Cdd:smart00750  81 YTE-----KADIYSLGITLYEALDYELPYNEERELSAILEILLNGMPADDPRDRSNLEGVSAARS-FEDFMRLC-ASRLP 153

                          170       180
                   ....*....|....*....|...
gi 2462517218  173 HIRRLVGLVLGTISEVEKRVVEE 195
Cdd:smart00750 154 QRREAANHYLAHCRALFAETLEL 176

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 2462517218 543 GVLVHQVFSEKRRPEEEMALGICAKGVIVYEVKNNSRIAMLRFQWRETGKISTYQKKFTITSSV-TGKKHTFVTDSAKTS 621
Cdd:cd13187     1 GVHFHRVYREKKSSTLSLWLGICSRGIIIYEEKNGARTPVLRFPWRETQKISFDKKKFTIESRGgSGIKHTFYTDSYKKS 80

                          90       100
                  ....*....|....*....|...
gi 2462517218 622 KYLLDLCSAQHGFNAQMGSGQPS 644
Cdd:cd13187    81 QYLLQLCSAQHKFHIQMRSRQST 103

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 2462517218 340 RDLCVVLLNGQHLEVKCDVESTVGAVFNAVTSFANLEELTYFGLAYMKSKEFFFLDSETRLCKIAPEGWREQPQK---TS 416
Cdd:cd17101     2 RYVNVVLLNGQRLQVAVDVKTTVQDLFDQVCDHLGLQETELFGLAVLKDGEYFFLDPDTKLSKYAPKGWKSEAKKglkGG 81

                          90
                  ....*....|....*.
gi 2462517218 417 MNTFTLFLRIKFFVSH 432
Cdd:cd17101    82 KPVFTLYFRVKFYVDN 97

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 2462517218 340 RDLCVVLLNGQHLEVKCDVESTVGAVFNAVTSFANLEELTYFGLAYMKSKEFFFLDSETRLCKIAPEGWREQPQKTSMNT 419
Cdd:cd17195     2 RKVNIMLLSGQRLELTCDTKSTCKDVFDMVVAHIGLVEHHLFALAYLKDNEFFFVDPDLKLSKVAPEGWKEEPKKKNKMT 81

                          90
                  ....*....|...
gi 2462517218 420 --FTLFLRIKFFV 430
Cdd:cd17195    82 vnFTLFFRIKFFV 94

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 2462517218 441 TRHQFYLQLRKDILEERLYCNEEILLQLGVLALQAEFGNYPKEVESKPYFHVEDYIPASLIERMTALRVQVEVSEMHRLS 520
Cdd:cd14473     1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKPEEWEKRIVELHKKL 80

                          90
                  ....*....|....*....
gi 2462517218 521 SALWGEDAELKFLRVTQQL 539
Cdd:cd14473    81 RGLSPAEAKLKYLKIARKL 99

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 2462517218 549 VFSEKRRPEEEMALGICAKGVIVYEVKNNSRIAMLRFQWRETGKISTYQKKFTITSSVTGKKHTFVTDSAKTSKYLLDLC 628
Cdd:cd13185    10 LRKSKKETPGSVLLGITAKGIQIYQESDGEQQLLRTFPWSNIGKLSFDRKKFEIRPEGSLRKLTYYTSSDEKSKYLLALC 89

                  ....*..
gi 2462517218 629 SAQHGFN 635
Cdd:cd13185    90 RETHQFS 96

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 2462517218 542 YGVLVhqvFSEKRRPEEEMALGICAKGVIVYEvKNNSRIAMLRFQWRETGKISTYQKKFTItSSVTGKKHTFV--TDSAK 619
Cdd:cd13194     2 YGVNY---FEIKNKKGTDLWLGVDALGLNIYE-PDNKLTPKIGFPWSEIRNISFNDKKFVI-KPIDKKAPDFVfySPRLR 76

                          90
                  ....*....|...
gi 2462517218 620 TSKYLLDLCSAQH 632
Cdd:cd13194    77 INKRILDLCMGNH 89

FERM domain C-lobe of Protein tyrosine phosphatase non-receptor proteins 14 and 21 (PTPN14 and 21); This CD contains PTP members: pez/PTPN14 and PTPN21. A number of mutations in Pez have been shown to be associated with breast and colorectal cancer. The PTPN protein family belong to larger family of PTPs. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. The members are composed of a N-terminal FERM domain and a C-terminal PTP catalytic 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. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. 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 2462517218 550 FSEKRRPEEEMALGICAKGVIVyevKNNSRIAMLRFQWRETGKISTYQKKFTITSSVTGKKHTFVTDSAKTSKYLLDLCS 629
Cdd:cd13188     6 FPAKDEQGNEVLIGASLEGIFV---KHDNGRPPVFFRWEDIKNVINHKRTFSIECQNSEETVQFQFEDAETAKYVWKLCV 82

                  ....*
gi 2462517218 630 AQHGF 634
Cdd:cd13188    83 LQHKF 87

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing proteins FRMD4A, FRMD4B, and similar proteins; This family includes FERM domain-containing proteins FRMD4A and FRMD4B, both of which 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). FRMD4A is a cytohesin adaptor involved in cell structure, transport and signaling. It promotes the growth of cancer cells in tongue, head and neck squamous cell carcinomas. FRMD4B, also termed GRP1-binding protein GRSP1, interacts with the coil-coil domain of ARF exchange factor GRP1 to form the Grsp1-Grp1 complex that co-localizes with cortical actin rich regions in response to stimulation of CHO-T cells with insulin or epidermal growth factor (EGF).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462517218 340 RDLCVVLLNGQHLEVKCDVESTVGAVFNAVTSFANLEELTYFGLAYMKSKEFF-FLDSETRLCKiapegwREQPQKTSMN 418
Cdd:cd17103     3 RRCQVVLLDDRRLEILVQPKLLAGDLLDLVASHFNLKEKEYFGLAYEDETGHYnWLQLDKRVLD------HEFPKKWSSG 76

                          90
                  ....*....|....*
gi 2462517218 419 TFTLFLRIKFFVSHY 433
Cdd:cd17103    77 PLVLHFAVKFYVESI 91

FERM domain C-lobe of Protein 4.1 family; The protein 4.1 family includes four well-defined members: erythroid protein 4.1 (4.1R), the best known and characterized member, 4.1G (general), 4.1N (neuronal), and 4.1 B (brain). The less well understood 4.1O/FRMD3 is not a true member of this family and is not included in this hierarchy. Besides three highly conserved domains, FERM, SAB (spectrin and actin binding domain) and CTD (C-terminal domain), the proteins from this family contain several unique domains: U1, U2 and U3. FERM domains like other members of the FERM domain superfamily have a cloverleaf architecture with three distinct lobes: (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 brain is a particularly rich source of protein 4.1 isoforms. The various 4.1R, 4.1G, 4.1N, and 4.1B mRNAs are all expressed in distinct patterns within the brain. It is likely that 4.1 proteins play important functional roles in the brain including motor coordination and spatial learning, postmitotic differentiation, and synaptic architecture and function. In addition they are found in nonerythroid, nonneuronal cells where they may play a general structural role in nuclear architecture and/or may interact with splicing factors. The FERM C domain is the third structural domain within the FERM domain. 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.

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gi 2462517218 542 YGVLVHQVFSEKrrpEEEMALGICAKGVIVYEvknnSRIAMLRFQWRETGKISTYQKKFTITSSVT-----GKKHTFVTD 616
Cdd:cd13184     1 YGVDLHPAKDSE---GVDIMLGVCSSGLLVYR----DRLRINRFAWPKVLKISYKRNNFYIKIRPGefeqyETTIGFKLP 73

                          90
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gi 2462517218 617 SAKTSKYLLDLCSAQHGF 634
Cdd:cd13184    74 NHRAAKRLWKVCVEHHTF 91