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 2401795874 200 MYGVNYFEIKNKKGTELWLGVDALGLNIYEHEDKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYAPRLRINKR 279
Cdd:cd13194     1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                          90
                  ....*....|....*..
gi 2401795874 280 ILALCMGNHELYMRRRK 296
Cdd:cd13194    81 ILDLCMGNHELYMRRRK 97

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 2401795874    7 VRVTTMDAE-LEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVD-SKGYSTWLKLNKKVTAQDVKKEnPLQFKFRAKF 84
Cdd:smart00295   2 LKVYLLDGTtLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDpDEDLRHWLDPAKTLLDQDVKSE-PLTLYFRVKF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874   85 FPEDVsEELIQEITQ-RLFFLQVKEAILNDENYCPPETAVLLASYSVQAKYADYNKDSH-KPGYLTNDRLLPQRVLEQhk 162
Cdd:smart00295  81 YPPDP-NQLKEDPTRlNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHdLRGELSLKRFLPKQLLDS-- 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 2401795874  163 LTKEQWEDRIQTWHEEHRGMLREDTMMEYLKIAQDLEMYGVNYF 206
Cdd:smart00295 158 RKLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874 345 DELMERLRLIEDQTMRAQKglfsapELEEQTRRALELEQERKRAREEAERLERERQAAEEAKAELARQAADQMKNQEQLA 424
Cdd:pfam20492   9 QELEERLKQYEEETKKAQE------ELEESEETAEELEEERRQAEEEAERLEQKRQEAEEEKERLEESAEMEAEEKEQLE 82

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2401795874 425 AELGEFTAKIALLEEAKRKKDEEATEWQQKAISAQDDL 462
Cdd:pfam20492  83 AELAEAQEEIARLEEEVERKEEEARRLQEELEEAREEE 120

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 2401795874 200 MYGVNYFEIKNKKGTELWLGVDALGLNIYEHEDKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYAPRLRINKR 279
Cdd:cd13194     1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                          90
                  ....*....|....*..
gi 2401795874 280 ILALCMGNHELYMRRRK 296
Cdd:cd13194    81 ILDLCMGNHELYMRRRK 97

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 2401795874    7 VRVTTMDAE-LEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVD-SKGYSTWLKLNKKVTAQDVKKEnPLQFKFRAKF 84
Cdd:smart00295   2 LKVYLLDGTtLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDpDEDLRHWLDPAKTLLDQDVKSE-PLTLYFRVKF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874   85 FPEDVsEELIQEITQ-RLFFLQVKEAILNDENYCPPETAVLLASYSVQAKYADYNKDSH-KPGYLTNDRLLPQRVLEQhk 162
Cdd:smart00295  81 YPPDP-NQLKEDPTRlNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHdLRGELSLKRFLPKQLLDS-- 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 2401795874  163 LTKEQWEDRIQTWHEEHRGMLREDTMMEYLKIAQDLEMYGVNYF 206
Cdd:smart00295 158 RKLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

Ezrin/radixin/moesin family C terminal; This entry represents the C-terminal domain of the ERM family of proteins which consists of three closely-related proteins, ezrin, radixin and moesin. These proteins link actin filaments of cell surface structures to the plasma membrane, using a C-terminal F-actin binding segment and an N-terminal FERM domain (pfam00373), a common membrane binding module. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). This entry represents the C-terminal actin-binding tail domain. This entry also includes Ermin proteins, oligodendrocyte-specific proteins associated with the cytoskeleton whose C-terminal domain is similar to that in ERM family.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2401795874 511 DLRSEEERVTEAQKNERLKKQLQVLSSELAEAIDDTMKTQNDMLHAENVKAGRDKYKTLRQIRLGNTKQRIDEFESM 587
Cdd:pfam00769   1 SLEIEEERVTYAEKNKRLQEQLKELKSELAQARDETKQTALDILHEENVRQGRDKYKTLRKIRQGNTKQRVDFFEEL 77

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 2401795874  98 TQRLFFLQVKEAILNDENYCPPETAVLLASYSVQAKYADYNKDSHKPGYLTNDRLLPQRVLEQHKLtkEQWEDRIQTWHE 177
Cdd:cd14473     1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKP--EEWEKRIVELHK 78

                          90       100
                  ....*....|....*....|.
gi 2401795874 178 EHRGMLREDTMMEYLKIAQDL 198
Cdd:cd14473    79 KLRGLSPAEAKLKYLKIARKL 99

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874 345 DELMERLRLIEDQTMRAQKglfsapELEEQTRRALELEQERKRAREEAERLERERQAAEEAKAELARQAADQMKNQEQLA 424
Cdd:pfam20492   9 QELEERLKQYEEETKKAQE------ELEESEETAEELEEERRQAEEEAERLEQKRQEAEEEKERLEESAEMEAEEKEQLE 82

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2401795874 425 AELGEFTAKIALLEEAKRKKDEEATEWQQKAISAQDDL 462
Cdd:pfam20492  83 AELAEAQEEIARLEEEVERKEEEARRLQEELEEAREEE 120

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874  292 MRRRKPDTIEVQQMKAQAREEKHHKQQERAQLENEKKKREHAEKEKERIEREKDELMERLRLIEDQTMRAQKGLFSAPEL 371
Cdd:PTZ00121  1307 AKKKAEEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAKKKADAAKKK 1386

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874  372 EEQTRRALEL----EQERKRAREEAERLERERQAAEEAKAELARQAADQMKNQEQLAAELGEFTAKIA---LLEEAKRKK 444
Cdd:PTZ00121  1387 AEEKKKADEAkkkaEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEeakKAEEAKKKA 1466

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874  445 DE--EATEWQQKAISAQ--DDLEKTKEELKTvmtisstpagGSTESEHEEQDENHAEDAAELSlEGVSALDLRSEEE--R 518
Cdd:PTZ00121  1467 EEakKADEAKKKAEEAKkaDEAKKKAEEAKK----------KADEAKKAAEAKKKADEAKKAE-EAKKADEAKKAEEakK 1535

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2401795874  519 VTEAQKNERLKKQLQVLSSELAEAIDDTMKTQNDMLHAENVKAGRDKYKTLRQIRlgntKQRIDE 583
Cdd:PTZ00121  1536 ADEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKAEEAKKAE----EARIEE 1596

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 2401795874 200 MYGVNYFEIKNKKGTELWLGVDALGLNIYEHEDKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYAPRLRINKR 279
Cdd:cd13194     1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                          90
                  ....*....|....*..
gi 2401795874 280 ILALCMGNHELYMRRRK 296
Cdd:cd13194    81 ILDLCMGNHELYMRRRK 97

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 2401795874    7 VRVTTMDAE-LEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVD-SKGYSTWLKLNKKVTAQDVKKEnPLQFKFRAKF 84
Cdd:smart00295   2 LKVYLLDGTtLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDpDEDLRHWLDPAKTLLDQDVKSE-PLTLYFRVKF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874   85 FPEDVsEELIQEITQ-RLFFLQVKEAILNDENYCPPETAVLLASYSVQAKYADYNKDSH-KPGYLTNDRLLPQRVLEQhk 162
Cdd:smart00295  81 YPPDP-NQLKEDPTRlNLLYLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHdLRGELSLKRFLPKQLLDS-- 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 2401795874  163 LTKEQWEDRIQTWHEEHRGMLREDTMMEYLKIAQDLEMYGVNYF 206
Cdd:smart00295 158 RKLKEWRERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in radixin and similar proteins; Radixin is a member of the ezrin/radixin/moesin (ERM) family of cytoskeletal proteins that plays 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. The C-terminal domain can fold back to bind to the FERM domain forming an autoinhibited conformation. 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). Radixin plays important roles in cell polarity, cell motility, invasion and tumor progression. It mediates the binding of F-actin to the plasma membrane after a conformational activation through Akt2-dependent phosphorylation at Thr564. It is also involved in reversal learning and short-term memory by regulating synaptic GABAA receptor density.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874   5 INVRVTTMDAELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQDVKKENPLQFKFRAKF 84
Cdd:cd17238     1 INVRVTTMDAELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTQQDVKKENPLQFKFRAKF 80

                  ...
gi 2401795874  85 FPE 87
Cdd:cd17238    81 FPE 83

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874   5 INVRVTTMDAELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQDVKKENPLQFKFRAKF 84
Cdd:cd17097     1 INVRVTTMDAELEFSIKPKAKGRELFDLVCRTIGLRETWYFGLQYENKKGRVAWLKPDKKVLTQDVSKNNTLKFFFLVKF 80

                  ...
gi 2401795874  85 FPE 87
Cdd:cd17097    81 YPE 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874  88 DVSEELIQEITQRLFFLQVKEAILNDENYCPPETAVLLASYSVQAKYADYNKDSHKPGYLTNDRLLPQRVleQHKLTKEQ 167
Cdd:pfam00373   1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQL--LRKMKSKE 78

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2401795874 168 WEDRIQTWHEEHRGMLREDTMMEYLKIAQDLEMYGVNYF 206
Cdd:pfam00373  79 LEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874 210 NKKGTELWLGVDALGLNIYEHEDKLtpKIGFPWSEIRNISFNDKKFVIKPIDKKAPD-FVFYAPRLRINKRILALCMGNH 288
Cdd:pfam09380   1 DKEGTDLWLGVSAKGILVYEDNNKI--LNLFPWREIRKISFKRKKFLIKLRDKSSEEtLGFYTESSRACKYLWKLCVEQH 78

                  ....*..
gi 2401795874 289 ELYMRRR 295
Cdd:pfam09380  79 TFFRLRR 85

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 2401795874  98 TQRLFFLQVKEAILNDENYCPPETAVLLASYSVQAKYADYNKDSHKPGYLTNDRLLPQRVLEQHKLtkEQWEDRIQTWHE 177
Cdd:cd14473     1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLKQRKP--EEWEKRIVELHK 78

                          90       100
                  ....*....|....*....|.
gi 2401795874 178 EHRGMLREDTMMEYLKIAQDL 198
Cdd:cd14473    79 KLRGLSPAEAKLKYLKIARKL 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 2401795874   5 INVRVTTMD-AELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQdVKKENPLQFKFRAK 83
Cdd:cd01765     1 ISCRVRLLDgTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEDNDGQKHWLDLDKKISKQ-LKRSGPYQFYFRVK 79

                  .
gi 2401795874  84 F 84
Cdd:cd01765    80 F 80

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 2401795874   5 INVRVTTMD-AELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQdVKKENPLQFKFRAK 83
Cdd:cd17098     1 LHVKVQMLDdTVHIFQVQQKALGEVLFDQVCKHLNLLESDYFGLEFTDPEGNKCWLDPEKPILRQ-VKRPKDVVFKFVVK 79

                  ....*
gi 2401795874  84 FFPED 88
Cdd:cd17098    80 FYTPD 84

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874 345 DELMERLRLIEDQTMRAQKglfsapELEEQTRRALELEQERKRAREEAERLERERQAAEEAKAELARQAADQMKNQEQLA 424
Cdd:pfam20492   9 QELEERLKQYEEETKKAQE------ELEESEETAEELEEERRQAEEEAERLEQKRQEAEEEKERLEESAEMEAEEKEQLE 82

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2401795874 425 AELGEFTAKIALLEEAKRKKDEEATEWQQKAISAQDDL 462
Cdd:pfam20492  83 AELAEAQEEIARLEEEVERKEEEARRLQEELEEAREEE 120

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 2401795874 206 FEIKNKKGTELWLGVDALGLNIYE-HEDKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYAPRLRINKRILALC 284
Cdd:cd13187     8 YREKKSSTLSLWLGICSRGIIIYEeKNGARTPVLRFPWRETQKISFDKKKFTIESRGGSGIKHTFYTDSYKKSQYLLQLC 87

                          90
                  ....*....|....*
gi 2401795874 285 MGNHE--LYMRRRKP 297
Cdd:cd13187    88 SAQHKfhIQMRSRQS 102

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 4B (FRMD4B); 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). FRMD4B contains a FERM protein interaction domain as well as two coiled coil domains and may therefore function as a scaffolding protein. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2401795874  13 DAELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQDV-KKENPLQFKFRAKFFPEDV 89
Cdd:cd17200    12 DRKLELLVQPKLLSRELLDLVASHFNLKEKEYFGITFIDDTGQSNWLQLDHRVLDHDLpKKSGPVTLYFAVRFYIESI 89

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like 5 (EPB41L5) and similar proteins; This family includes FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like proteins, EPB41L5 and EPB41L4B. EPB41L5 is a mesenchymal-specific protein that is an integral component of the ARF6-based pathway. 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. Both EPB41L5 and EPB41L4B 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 2401795874   5 INVRVTTMD-AELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQdVKKENPLQFKFRAK 83
Cdd:cd17108     1 IQCKVILLDgTDLSIELPKKAKGQELYEQVFYHLDLIEKDYFGLQFMDAAQVQHWLDPTKKIKKQ-VKIGPPYTLRFRVK 79

                  ..
gi 2401795874  84 FF 85
Cdd:cd17108    80 FY 81

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 7 (FRMD7); FRMD7 plays an important role in neuronal development and is involved in the regulation of F-actin, neurofilament, and microtubule dynamics. It interacts with the Rho GTPase regulator, RhoGDIalpha, and activates the Rho subfamily member Rac1, which regulates reorganization of actin filaments and controls neuronal outgrowth. Mutations in the FRMD7 gene are responsible for the X-linked idiopathic congenital nystagmus (ICN), a disease which affects ocular motor control. FRMD7 contains a FERM domain, and a pleckstrin homology (PH) 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 2401795874  13 DAELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQdVKKENPLQFKFRAKFFPED 88
Cdd:cd17188    11 DSQKVFVVDQKSTGKDLFNMSCSHLNLVEKEYFGLEFRNHAGNNVWLELLKPITKQ-IKNPKELIFKFTVKFFPVD 85

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 2401795874   8 RVTTMDA-ELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQdvKKENPLQFKFRAKFFP 86
Cdd:cd17201     5 KVTLLDGsEYECEVEKHARGQVLFDTVCEHLNLLEKDYFGLTFCDTESQKNWLDPSKEIKKQ--IRSGPWHFAFTVKFYP 82

                  ..
gi 2401795874  87 ED 88
Cdd:cd17201    83 PD 84

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2401795874 194 IAQDLEMYGVNYFEIKNKKGTELWLGVDALGLNIYEHEDKLTpkiGFPWSEIRNISFNDKKFVIK 258
Cdd:cd13193     2 TARRCELYGIRLHPAKDREGVKLNLAVAHMGILVFQGFTKIN---TFSWAKIRKLSFKRKRFLIK 63

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2401795874 200 MYGVNYFEIKNKKGTELWLGVDALGLNIYEHEDKLTPkigFPWSEIRNISFNDKKFVI 257
Cdd:cd13189     1 LYGVELHSARDSNNLELQIGVSSAGILVFQNGIRINT---FPWSKIVKISFKRKQFFI 55

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 2401795874   5 INVRVTTMD-AELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQdVKKENPLQFKFRAK 83
Cdd:cd17190     1 LQLRVKLLDnTTEPLEIEPKADGQALLSQVFKRLNLVESDYFGLEFQNSQSNWIWLEPMKLIVKQ-VRRPKNTKLRLAVK 79

                  ....*
gi 2401795874  84 FFPED 88
Cdd:cd17190    80 FFPPD 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like proteins; The family includes erythrocyte membrane protein band 4.1-like proteins EPB41L1/4.1N, EPB41L2/4.1G, and EPB41L3/4.1B. They belong to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L1 is a cytoskeleton-associated protein that may serve as a tumor suppressor in solid tumors. EPB41L2 is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L3 also acts as a tumor suppressor implicated in a variety of meningiomas and carcinomas. Members in this family contain 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 2401795874   7 VRVTTMDA-ELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQdvKKENPLQFKFRAKFF 85
Cdd:cd17106     4 CKVLLLDGtEYTCEVEKRAKGQVLFDKVCEHLNLLEKDYFGLTYRDAQDQKNWLDPAKEIKKQ--IRSGPWLFSFNVKFY 81

                  ...
gi 2401795874  86 PED 88
Cdd:cd17106    82 PPD 84

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in erythrocyte membrane protein band 4.1-like protein 3 (EPB41L3) and similar proteins; EPB41L3, also termed 4.1B, or differentially expressed in adenocarcinoma of the lung protein 1 (DAL-1), belongs to the skeletal protein 4.1 family that is involved in cellular processes such as cell adhesion, migration and signaling. EPB41L3 is a tumor suppressor that has been implicated in a variety of meningiomas and carcinomas. EPB41L3 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 2401795874   8 RVTTMD-AELEFAIQPNTTGKQLFDQVVKTVGLREVWFFGLQYVDSKGYSTWLKLNKKVTAQdvKKENPLQFKFRAKFFP 86
Cdd:cd17203     5 KVTLLDgSEYTCEVEKRSKGQVLFDKVCEHLNLLEKDYFGLTYRDSENQKNWLDPAKEIKKQ--IRSGAWQFSFNVKFYP 82

                  ..
gi 2401795874  87 ED 88
Cdd:cd17203    83 PD 84

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874 289 ELYMRRRKPDTIEVQQMKAQAREEKHHKQQERAQLENEKKKREHAEKEKERIEREKDELMERLRLIEDQTMRAQkglfSA 368
Cdd:COG1196   289 EEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAE----AE 364

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874 369 PELEEQTRRALELEQERKRAREEAERLERERQAAEEAKAELARQAADQMKNQEQLAAELGEftakialLEEAKRKKDEEA 448
Cdd:COG1196   365 EALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEE-------LEEALAELEEEE 437

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2401795874 449 TEWQQKAISAQDDLEKTKEELKTvMTISSTPAGGSTESEHEEQDENHAEDAAELSLEGVSALDLRSEEERVtEAQKNERL 528
Cdd:COG1196   438 EEEEEALEEAAEEEAELEEEEEA-LLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGFL-EGVKAALL 515

                         250
                  ....*....|....*..
gi 2401795874 529 KKQLQVLSSELAEAIDD 545
Cdd:COG1196   516 LAGLRGLAGAVAVLIGV 532