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 442617466  251 ETARRCELYGMKMHPAKDVEGVPLNLAVAHMGITVFQNITRINTFSWAKIRKISFKRKRFLVKLHPEGYGYYKDTVEFFF 330
Cdd:cd13193     1 ETARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFLIKLHPEAYGSYKDTVEFSF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 442617466  331 EGRNECKNFWKKCVENHGFFRCTAVQNTPRRKTRVLSRGSSF 372
Cdd:cd13193    81 ESRNECKSFWKKCIEHHAFFRCSEVPKPPSPKLRLFSRGSSF 122

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 442617466   364 RVLSRGSSFRYSGKTQKQIIEFVRENYVKRQNFQRSQSFRQ 404
Cdd:pfam08736    1 KFFSLGSKFRYSGRTQKQTVEDSSEILRPQPEFERSPSKRY 41

GRB2-binding adapter (GAPT); This is a family of transmembrane proteins which bind the growth factor receptor-bound protein 2 (GRB2) in B cells. In contrast to other transmembrane adaptor proteins, GAPT is not phosphorylated upon BCR ligation. It associates with GRB2 constitutively through its proline-rich region.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 442617466  1240 KSKTSVaSSQDSKESLVGDCFGRNYEMPTTTGKKVKQFTKKELYEKFAQSS-------QESKSDYYD 1299
Cdd:pfam11770   71 KHKISV-QTQDHRSAVKGTNIHDNYENVEVGPPKAKEETDKELYENTRQSNfeehiygNETSSEYYN 136

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 442617466  251 ETARRCELYGMKMHPAKDVEGVPLNLAVAHMGITVFQNITRINTFSWAKIRKISFKRKRFLVKLHPEGYGYYKDTVEFFF 330
Cdd:cd13193     1 ETARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFLIKLHPEAYGSYKDTVEFSF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 442617466  331 EGRNECKNFWKKCVENHGFFRCTAVQNTPRRKTRVLSRGSSF 372
Cdd:cd13193    81 ESRNECKSFWKKCIEHHAFFRCSEVPKPPSPKLRLFSRGSSF 122

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, RhoGEF and pleckstrin domain-containing protein 1 (FARP1) and similar proteins; This family includes the F1 sub-domain of FERM, RhoGEF and pleckstrin domain-containing proteins FARP1, FARP2, and FERM domain-containing protein 7 (FRMD7). FARP1, also termed chondrocyte-derived ezrin-like protein (CDEP), or pleckstrin homology (PH) domain-containing family C member 2 (PLEKHC2), is a neuronal activator of the RhoA GTPase. It promotes outgrowth of developing motor neuron dendrites. It also regulates excitatory synapse formation and morphology, as well as activates the GTPase Rac1 to promote F-actin assembly. FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FRMD7 plays an important role in neuronal development and is involved in the regulation of F-actin, neurofilament, and microtubule dynamics. All family members contain a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to 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 442617466   69 LTVRIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEVStHTKYWLDLEKPMNRQVGLsLIDPVLRFCI 148
Cdd:cd17098     1 LHVKVQMLDDTVHIFQVQQKALGEVLFDQVCKHLNLLESDYFGLEFTDPE-GNKCWLDPEKPILRQVKR-PKDVVFKFVV 78

                  ....*..
gi 442617466  149 KFYTPDP 155
Cdd:cd17098    79 KFYTPDP 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   153 PDPAQLEEEYTRYLFCLQIKRDLATGSLQCNDNTAALMASYIVQASCGDFVPEDYPdHTYLSSYRFVPNQDAT------M 226
Cdd:pfam00373    1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHT-SEYLSLESFLPKQLLRkmkskeL 79

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 442617466   227 QRKIMENHKKHVGQSPAEADLNLLETARRCELYGMKMH 264
Cdd:pfam00373   80 EKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466 2219 KTSEPYKGKPVSRSRPESRRTSADDIKARDGrgSKKSSPKERPRSIEMRRLSKDKSKSQEETEADIAKRKERQQKLYESA 2298
Cdd:PTZ00121 1385 KKAEEKKKADEAKKKAEEDKKKADELKKAAA--AKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEA 1462

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466 2299 MK------QTITMLSPVKDTLPAFPAPGDKILVKTDGDKIIIETEFKSKAE-----------DHVLIAKSPRKLDNSL-V 2360
Cdd:PTZ00121 1463 KKkaeeakKADEAKKKAEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADeakkaeeakkaDEAKKAEEAKKADEAKkA 1542

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466 2361 KFSRSFDEGRSPDKLDKAN---------RSFEDRNKSFEDS------EKSDAPEDMLIKSPKKIAKAQELKQKIEGSVvh 2425
Cdd:PTZ00121 1543 EEKKKADELKKAEELKKAEekkkaeeakKAEEDKNMALRKAeeakkaEEARIEEVMKLYEEEKKMKAEEAKKAEEAKI-- 1620

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466 2426 kkidgKSSSLERPAEHHYLGPDVKARSLDDKRQATEAAKKNEEKPapvVRSAIGDRRMFAHQYQVQEPHQEDIDmqavis 2505
Cdd:PTZ00121 1621 -----KAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENK---IKAAEEAKKAEEDKKKAEEAKKAEED------ 1686

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466 2506 ERRSLEILKRSlpSEDARDSEgafSRKPSTAESLDSYVSVDEShsaaskspvpgtgggtegypHRVPTIECEEPSIEEDE 2585
Cdd:PTZ00121 1687 EKKAAEALKKE--AEEAKKAE---ELKKKEAEEKKKAEELKKA--------------------EEENKIKAEEAKKEAEE 1741

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466 2586 NSSERRHLKVGGQDTNRLSLDRSRSDETGSWMTVECDEFI--GSDTSDnEPRTLEPDRNVLETQATLE-------DANPl 2656
Cdd:PTZ00121 1742 DKKKAEEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIeeELDEED-EKRRMEVDKKIKDIFDNFAniieggkEGNL- 1819

                         490       500       510       520       530       540
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466 2657 eYSNCATPTSDLNILLTPPNASPQIEKSVLETFEKYTGSSDTGKKKNtldKQSDRSKSSD 2716
Cdd:PTZ00121 1820 -VINDSKEMEDSAIKEVADSKNMQLEEADAFEKHKFNKNNENGEDGN---KEADFNKEKD 1875

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 442617466  251 ETARRCELYGMKMHPAKDVEGVPLNLAVAHMGITVFQNITRINTFSWAKIRKISFKRKRFLVKLHPEGYGYYKDTVEFFF 330
Cdd:cd13193     1 ETARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKINTFSWAKIRKLSFKRKRFLIKLHPEAYGSYKDTVEFSF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 442617466  331 EGRNECKNFWKKCVENHGFFRCTAVQNTPRRKTRVLSRGSSF 372
Cdd:cd13193    81 ESRNECKSFWKKCIEHHAFFRCSEVPKPPSPKLRLFSRGSSF 122

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, RhoGEF and pleckstrin domain-containing protein 1 (FARP1) and similar proteins; This family includes the F1 sub-domain of FERM, RhoGEF and pleckstrin domain-containing proteins FARP1, FARP2, and FERM domain-containing protein 7 (FRMD7). FARP1, also termed chondrocyte-derived ezrin-like protein (CDEP), or pleckstrin homology (PH) domain-containing family C member 2 (PLEKHC2), is a neuronal activator of the RhoA GTPase. It promotes outgrowth of developing motor neuron dendrites. It also regulates excitatory synapse formation and morphology, as well as activates the GTPase Rac1 to promote F-actin assembly. FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FRMD7 plays an important role in neuronal development and is involved in the regulation of F-actin, neurofilament, and microtubule dynamics. All family members contain a FERM domain that is made up of three sub-domains, F1, F2, and F3. This family corresponds to 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 442617466   69 LTVRIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEVStHTKYWLDLEKPMNRQVGLsLIDPVLRFCI 148
Cdd:cd17098     1 LHVKVQMLDDTVHIFQVQQKALGEVLFDQVCKHLNLLESDYFGLEFTDPE-GNKCWLDPEKPILRQVKR-PKDVVFKFVV 78

                  ....*..
gi 442617466  149 KFYTPDP 155
Cdd:cd17098    79 KFYTPDP 85

FERM C-terminal PH-like domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   268 DVEGVPLNLAVAHMGITVFQNITRI-NTFSWAKIRKISFKRKRFLVKLHpegYGYYKDTVEFFFEGRNECKNFWKKCVEN 346
Cdd:pfam09380    1 DKEGTDLWLGVSAKGILVYEDNNKIlNLFPWREIRKISFKRKKFLIKLR---DKSSEETLGFYTESSRACKYLWKLCVEQ 77

                   ....*.
gi 442617466   347 HGFFRC 352
Cdd:pfam09380   78 HTFFRL 83

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 442617466  163 TRYLFCLQIKRDLATGSLQCNDNTAALMASYIVQASCGDFVPEDYPDhTYLSSYRFVPNQ------DATMQRKIMENHKK 236
Cdd:cd14473     1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKP-KYLSLKRFLPKQllkqrkPEEWEKRIVELHKK 79

                          90       100
                  ....*....|....*....|
gi 442617466  237 HVGQSPAEADLNLLETARRC 256
Cdd:cd14473    80 LRGLSPAEAKLKYLKIARKL 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 442617466   69 LTVRIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYqEVSTHTKYWLDLEKPMNRQVgLSLIDPVLRFCI 148
Cdd:cd01765     1 ISCRVRLLDGTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFY-EDNDGQKHWLDLDKKISKQL-KRSGPYQFYFRV 78

                  ..
gi 442617466  149 KF 150
Cdd:cd01765    79 KF 80

FERM domain C-lobe of FERM domain-containing protein 3 and 5 (FRMD3 and 5); FRMD3 (also called Band 4.1-like protein 4O/4.1O though it is not a true member of that family) is a novel putative tumor suppressor gene that is implicated in the origin and progression of lung cancer. In humans there are 5 isoforms that are produced by alternative splicing. Less is known about FRMD5, though there are 2 isoforms of the human protein are produced by alternative splicing. Both FRMD3 and FRMD5 contain a N-terminal FERM domain, followed by a FERM adjacent (FA) domain, and 4.1 protein C-terminal domain (CTD). 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 442617466  245 ADLNLLETARRCELYGMKMHPAKDVEGVPLNLAVAHMGITVFQNITRINTFSWAKIRKISFKRKRFLVKLHPEgyGYYKD 324
Cdd:cd13192     1 AEDNFLRKAATLETYGVDPHPVKDHRGNQLYLGFTHTGIVTFQGGKRVHHFRWNDITKFNYEGKMFILHVMQK--EEKKH 78

                          90       100
                  ....*....|....*....|....*..
gi 442617466  325 TVEFFFEGRNECKNFWKKCVENHGFFR 351
Cdd:cd13192    79 TLGFKCPTPAACKHLWKCAVEQQAFYT 105

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM, ARH/RhoGEF and pleckstrin domain-containing protein 2 (FARP2) and similar proteins; FARP2, also termed FERM domain including RhoGEF (FIR), or Pleckstrin homology (PH) domain-containing family C member 3, is a Dbl-family guanine nucleotide exchange factor (GEF) that activates Rac1 or Cdc42 in response to upstream signals, suggesting roles in regulating processes such as neuronal axon guidance and bone homeostasis. It is also a key molecule involved in the response of neuronal growth cones to class-3 semaphorins. FARP2 contains a FERM domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) 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 442617466   69 LTVRIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEVSTHtKYWLDLEKPMNRQVGLSLiDPVLRFCI 148
Cdd:cd17190     1 LQLRVKLLDNTTEPLEIEPKADGQALLSQVFKRLNLVESDYFGLEFQNSQSN-WIWLEPMKLIVKQVRRPK-NTKLRLAV 78

                  ....*..
gi 442617466  149 KFYTPDP 155
Cdd:cd17190    79 KFFPPDP 85

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        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   71 VRIQMLDDSITMFQVQAK-ALGRVLFEQVCRQLNLLEADYFGLEYQEVSTHtKYWLDLEKPMNRQVglSLIDP-VLRFCI 148
Cdd:cd17102     3 CTIRLLDDSEVICCEFKKdTKGQFLLDYVCNYLNLLEKDYFGLRYVDTEKQ-RHWLDPNKSIYKQL--KGVPPyVLCFRV 79

                  ...
gi 442617466  149 KFY 151
Cdd:cd17102    80 KFY 82

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 3 (PTPN3) and similar proteins; This family includes two tyrosine-protein phosphatase non-receptors, PTPN3 and PTPN4, both of which belong to the non-transmembrane FERM-containing protein-tyrosine phosphatase (PTP) subfamily characterized by a conserved N-terminal FERM domain, a PDZ domain, 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).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   69 LTVRIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEVS--THTKYWLDLEKPMNRQVGLsliDPV--L 144
Cdd:cd17100     2 VRCIVHFLDDTEQTFEVEKRDKGQVLLDKVFNHLELVEKDYFGLQFSDDSpaTDSMRWLDPLKPIRKQIKG---GPPyyL 78

                  ....*..
gi 442617466  145 RFCIKFY 151
Cdd:cd17100    79 NFRVKFY 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band 4.1-like protein 4A (EPB41L4A) and similar proteins; EPB41L4A, also termed protein NBL4, is a member of the band 4.1/Nbl4 (novel band 4.1-like protein 4) group of the FERM protein superfamily. It 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). EPB41L4A is an important component of the beta-catenin/Tcf pathway. It may be related to determination of cell polarity or proliferation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   67 KKLTVRIQMLDDSITMFQVQAKAL----GRVLFEQVCRQLNLLEADYFGLEYQEvSTHTKYWLDLEKPMNRQvgLSLIDP 142
Cdd:cd17107     1 EEFYCEIVLLDESELILTIQQDGIksskGSVVLDVVFQHLNLLETDYFGLRYID-RQHQTHWLDPAKTLSEQ--LKLIGP 77

                          90
                  ....*....|....
gi 442617466  143 --VLRFCIKFYTPD 154
Cdd:cd17107    78 pyTLYFGVKFYAED 91

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   72 RIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEvSTHTKYWLDLEKPMNRQvgLSLIDPVLRFCIKFY 151
Cdd:cd17202     5 KVTLLDGTEYSCDLEKRAKGQVLFDKVCEHLNLLEKDYFGLLYQV-SANQKNWLDSTKEIKRQ--IRRLPWLFTFNVKFY 81

                  ...
gi 442617466  152 TPD 154
Cdd:cd17202    82 PPD 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1 (EPB41) and similar proteins; EPB41, also termed protein 4.1 (P4.1), or 4.1R, or Band 4.1, or EPB4.1, belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41 is a widely expressed cytoskeletal phosphoprotein that stabilizes the spectrin-actin cytoskeleton and anchors the cytoskeleton to the cell membrane. EPB41 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   72 RIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEVSThTKYWLDLEKPMNRQVGLSLIDpvLRFCIKFY 151
Cdd:cd17105     4 KVSLLDDTVYECEVEKHAKGQDLFKKVCEHLNLLEEDYFGLAIWDSPT-SKTWLDPAKEIKKQVHGGPWE--FTFNVKFY 80

                  ...
gi 442617466  152 TPD 154
Cdd:cd17105    81 PPD 83

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 1 (EPB41L1) and similar proteins; EPB41L1, also termed neuronal protein 4.1 (4.1N), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. It is a cytoskeleton-associated protein that may serve as a tumor suppressor in solid tumors. It suppresses hypoxia-induced epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) cells. The down-regulation of EPB41L1 expression is a critical step for non-small cell lung cancer (NSCLC) development. Moreover, EPB41L1 functions as a linker protein between inositol 1,4,5-trisphosphate receptor type1 (IP3R1) and actin filaments in neurons. EPB41L1 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   72 RIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEVSTHtKYWLDLEKPMNRQVGLSLIDpvLRFCIKFY 151
Cdd:cd17201     5 KVTLLDGSEYECEVEKHARGQVLFDTVCEHLNLLEKDYFGLTFCDTESQ-KNWLDPSKEIKKQIRSGPWH--FAFTVKFY 81

                  ...
gi 442617466  152 TPD 154
Cdd:cd17201    82 PPD 84

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   83 FQVQAKALGRVLFEQVCRQLNLLEADYFGLEYqEVSTHTKYWLDLEKPMNRQVGlSLIDPV-LRFCIKFY 151
Cdd:cd17097    14 FSIKPKAKGRELFDLVCRTIGLRETWYFGLQY-ENKKGRVAWLKPDKKVLTQDV-SKNNTLkFFFLVKFY 81

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 442617466   69 LTVRIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEVSTHTKyWLDLEKPMNRQVGLSLIDPVLRFCI 148
Cdd:cd17192     4 LVARIQLLNNEFVEFTLSVESTGQECLEAVAQRLELREITYFSLWYYNKQNQQR-WVDLEKPLKKQLDKYALEPTVYFGV 82

                  ....*
gi 442617466  149 KFYTP 153
Cdd:cd17192    83 VFYVP 87

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte band 4.1-like protein 4B (EPB41L4B); EPB41L4B, also termed FERM-containing protein CG1, or expressed in high metastatic cells (Ehm2), or Lulu2, is a member of the band 4.1/Nbl4 (novel band 4.1-like protein 4) group of the FERM protein superfamily. It 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). EPB41L4B is a positive regulator of keratinocyte adhesion and motility, suggesting a role in wound healing. It also promotes cancer metastasis in melanoma, prostate cancer and breast cancer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466   69 LTVRIQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEvSTHTKYWLDLEKPMNRQVGlslIDP--VLRF 146
Cdd:cd17204     1 LTCRVLLLDGTDVSVELPKHAKGQDLFDQIVYHLDLVETDYFGLQFMD-AAQVAHWLDHTKPIKKQIK---IGPpyTLHF 76

                  ....*.
gi 442617466  147 CIKFYT 152
Cdd:cd17204    77 RIKYYS 82

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in E3 ubiquitin-protein ligase MYLIP and similar proteins; MYLIP, also termed inducible degrader of the LDL-receptor (Idol), or myosin regulatory light chain interacting protein (MIR), is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Its activity depends on E2 ubiquitin-conjugating enzymes of the UBE2D family, including UBE2D1, UBE2D2, UBE2D3, and UBE2D4. MYLIP stimulates clathrin-independent endocytosis and acts as a sterol-dependent inhibitor of cellular cholesterol uptake by binding directly to the cytoplasmic tail of the LDLR and promoting its ubiquitination via the UBE2D1/E1 complex. The ubiquitinated LDLR then enters the multivesicular body (MVB) protein-sorting pathway and is shuttled to the lysosome for degradation. Moreover, MYLIP has been identified as a novel ERM-like protein that affects cytoskeleton interactions regulating cell motility, such as neurite outgrowth. The ERM proteins includes ezrin, radixin, and moesin, which are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. MYLIP contains a FERM-domain and a C-terminal C3HC4-type RING-HC finger. 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 442617466   77 DDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEvSTHTKYWLDLEKPMNRQVGlSLIDPVLRFCIKFY 151
Cdd:cd17104     9 DSVVIEVEVDPKANGQECLDKVCQKLGIIEKDYFGLQYTG-PKGERLWLNLRNRISRQLP-GPPPYRLRLRVKFF 81

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466  259 YGMKMHPAKDVEGVPLNLAVAHMGITVFQNITRIN-TFSWAKIRKISFKRKRFLVKLHPEGygyykDTVEFFFEGRNECK 337
Cdd:cd13188     1 YGEESFPAKDEQGNEVLIGASLEGIFVKHDNGRPPvFFRWEDIKNVINHKRTFSIECQNSE-----ETVQFQFEDAETAK 75

                          90
                  ....*....|....
gi 442617466  338 NFWKKCVENHGFFR 351
Cdd:cd13188    76 YVWKLCVLQHKFYR 89

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in tyrosine-protein phosphatase non-receptor type 3 (PTPN3); PTPN3, also termed protein-tyrosine phosphatase H1 (PTP-H1), belongs to the non-transmembrane FERM-containing protein-tyrosine phosphatase (PTP) subfamily characterized by a conserved N-terminal FERM domain, a PDZ domain, 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). PTPN3 associates with the mitogen-activated protein kinase p38gamma (also known as MAPK12) to form a PTPN3-p38gamma complex that promotes Ras-induced oncogenesis. It may also act as a tumor suppressor in lung cancer through its modulation of epidermal growth factor receptor (EGFR) signaling. Moreover, PTPN3 shows sensitizing effect to anti-estrogens. It dephosphorylates the tyrosine kinase EGFR, disrupts its interaction with the nuclear estrogen receptor, and increases breast cancer sensitivity to small molecule tyrosine kinase inhibitors (TKIs). It also cooperates with vitamin D receptor to stimulate breast cancer growth through their mutual stabilization.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 442617466   73 IQMLDDSITMFQVQAKALGRVLFEQVCRQLNLLEADYFGLEYQEVSTHTKYWLDLEKPMNRQV 135
Cdd:cd17193     6 VHFLDGSVQSFKVNKQDTGQVLLDMAYNHLGLTEREYFGLQHNEDSVDSPRWLEPSKPIRKQL 68

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617466 2217 KLKTSEPYKGKPVSRSRPESRRTSAddIKARDGR-------GSKKSSPKERPRSIEMRRLSKDKSKSQEETEADIAKRKE 2289
Cdd:PTZ00121 1247 EERNNEEIRKFEEARMAHFARRQAA--IKAEEARkadelkkAEEKKKADEAKKAEEKKKADEAKKKAEEAKKADEAKKKA 1324