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 32363191 212 MYGVNYFTIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKL 291
Cdd:cd13194   1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                        90
                ....*....|....*..
gi 32363191 292 ILQLCIGNHDLFMRRRK 308
Cdd:cd13194  81 ILDLCMGNHELYMRRRK 97

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 32363191   342 REEAERSRDEPERRVLHMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRL 421
Cdd:pfam20492   1 REEAEREKQELEERLKQYEEETKKAQEELEESEETAEELEEERRQAEEEAERLEQKRQEAEEEKERLEESAEMEAEEKEQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 32363191   422 MEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAE 461
Cdd:pfam20492  81 LEAELAEAQEEIARLEEEVERKEEEARRLQEELEEAREEE 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 32363191 212 MYGVNYFTIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKL 291
Cdd:cd13194   1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                        90
                ....*....|....*..
gi 32363191 292 ILQLCIGNHDLFMRRRK 308
Cdd:cd13194  81 ILDLCMGNHELYMRRRK 97

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in merlin and similar proteins; Merlin, also termed moesin-ezrin-radixin-like protein, or neurofibromin-2 (NF2), or Schwannomerlin, or Schwannomin, 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, merlin however lacks the typical actin-binding motif in the C-tail. 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 plays vital roles in controlling proper development of organ sizes by specifically binding to a large number of target proteins localized both in cytoplasm and nuclei. Merlin may function as a tumor suppressor that functions upstream of the core Hippo pathway kinases Lats1/2 (Wts in Drosophila) and Mst1/2 (Hpo in Drosophila), as well as the nuclear E3 ubiquitin ligase DDB1-and-Cullin 4-associated Factor 1 (DCAF1)-associated cullin 4-Roc1 ligase, CRL4(DCAF1). Merlin may also has a tumor suppressor function in melanoma cells, the inhibition of the proto-oncogenic Na(+)/H(+) exchanger isoform 1 (NHE1) activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191  16 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTI-KDTVAWLKMDKKVLDHDVSKEEPVTFHFLA 94
Cdd:cd17186   1 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTIGLRETWYFGLQYTDsKGTVAWLKMDKKVLDQDVPKEEPVTFHFLA 80

                ....*
gi 32363191  95 KFYPE 99
Cdd:cd17186  81 KFYPE 85

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191   222 NKKGTELLLGVDALGLHIYDPENRLtpKISFPWNEIRNISYSDKEFTIKPLDKKI-DVFKFNSSKLRVNKLILQLCIGNH 300
Cdd:pfam09380   1 DKEGTDLWLGVSAKGILVYEDNNKI--LNLFPWREIRKISFKRKKFLIKLRDKSSeETLGFYTESSRACKYLWKLCVEQH 78

                  ....*..
gi 32363191   301 DLFMRRR 307
Cdd:pfam09380  79 TFFRLRR 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32363191   514 SMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETALDILHSEHSDSGTsSKHNTIKK 575
Cdd:pfam00769   1 SLEIEEERVTYAEKNKRLQEQLKELKSELAQARDETKQTALDILHEENVRQGR-DKYKTLRK 61

cell envelope integrity inner membrane protein TolA; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191  314 VQQMKAQAREEKARKQMERQRLAREKQMREEAERSRDEPERRVLHMKEEATMANEALMRSEETADLLAEKAQITEEEAKL 393
Cdd:PRK09510  61 VEQYNRQQQQQKSAKRAEEQRKKKEQQQAEELQQKQAAEQERLKQLEKERLAAQEQKKQAEEAAKQAALKQKQAEEAAAK 140

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191  394 LAQKA-AEAEQEMQRIKATAIRTEEEKrlmeqKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIA 472
Cdd:PRK09510 141 AAAAAkAKAEAEAKRAAAAAKKAAAEA-----KKKAEAEAAKKAAAEAKKKAEAEAAAKAAAEAKKKAEAEAKKKAAAEA 215

                 ..
gi 32363191  473 TK 474
Cdd:PRK09510 216 KK 217

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191   315 QQMKAQAREEKARkQMERQRLAREKQMREEAERSRDEPERRVLHMKEEATMANEALMRSEETADLLAEKAQITEEEAKll 394
Cdd:TIGR02794  57 QQKKPAAKKEQER-QKKLEQQAEEAEKQRAAEQARQKELEQRAAAEKAAKQAEQAAKQAEEKQKQAEEAKAKQAAEAK-- 133

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 32363191   395 aqKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQK 467
Cdd:TIGR02794 134 --AKAEAEAERKAKEEAAKQAEEEAKAKAAAEAKKKAEEAKKKAEAEAKAKAEAEAKAKAEEAKAKAEAAKAK 204

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191    298 GNHDLFMRRRKADSLE--VQQMKAQAREEKARKQMERQRLAREKQMREEAERSRDEPERRVLHMKE-----EATMANEAL 370
Cdd:TIGR02168  668 TNSSILERRREIEELEekIEELEEKIAELEKALAELRKELEELEEELEQLRKELEELSRQISALRKdlarlEAEVEQLEE 747

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191    371 MRSEETADLLAEKAQITEEEAKL--LAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKV--LEAEVLALK--MAEESERRA 444
Cdd:TIGR02168  748 RIAQLSKELTELEAEIEELEERLeeAEEELAEAEAEIEELEAQIEQLKEELKALREALdeLRAELTLLNeeAANLRERLE 827

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191    445 KEADQLKQDLQEAREAERRAKQKLLEIATkpTYPPMNPIPAPLPPDIPSFDIIGDSLSFDFKDTDMKRLSMEIEKEKVEY 524
Cdd:TIGR02168  828 SLERRIAATERRLEDLEEQIEELSEDIES--LAAEIEELEELIEELESELEALLNERASLEEALALLRSELEELSEELRE 905

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 32363191    525 MEKSKH-LQEQLNELKTEIEALKLKERETALDILH 558
Cdd:TIGR02168  906 LESKRSeLRRELEELREKLAQLELRLEGLEVRIDN 940

pneumococcal surface protein PspC, choline-binding form; The pneumococcal surface protein PspC, as described in Streptococcus pneumoniae, is a repetitive and highly variable protein, recognized by a conserved N-terminal domain and also by genomic location. This form, subgroup 1, has variable numbers of a choline-binding repeat in the C-terminal region, and is also known as choline-binding protein A. The other form, subgroup 2, is anchored covalently after cleavage by sortase at a C-terminal LPXTG site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191  301 DLFMRRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERSRDEPERRVLHMKEEATMANEALMRSEETADLL 380
Cdd:NF033838 189 ELELVKEEAKEPRDEEKIKQAKAKVESKKAEATRLEKIKTDREKAEEEAKRRADAKLKEAVEKNVATSEQDKPKRRAKRG 268

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191  381 AEKAQIT----EEEAKLLA----------------QKAAEAEQEMQRIKATAIRTEEEKRL----------------MEQ 424
Cdd:NF033838 269 VLGEPATpdkkENDAKSSDssvgeetlpspslkpeKKVAEAEKKVEEAKKKAKDQKEEDRRnyptntyktleleiaeSDV 348

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191  425 KVLEAEVLALK--------------MAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIATKPTYPPMNPIPAPLP-P 489
Cdd:NF033838 349 KVKEAELELVKeeakeprneekikqAKAKVESKKAEATRLEKIKTDRKKAEEEAKRKAAEEDKVKEKPAEQPQPAPAPqP 428

                 ....
gi 32363191  490 DIPS 493
Cdd:NF033838 429 EKPA 432

polarized growth protein Scy;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191   329 QMERQRLARE-KQMREEA----ERSRDEPERR-VLHMKEEATMANEALMRSEETADLLAEKAQITEEEAKllaqkaAEAE 402
Cdd:NF041483  439 QEEARRLRGEaEQLRAEAvaegERIRGEARREaVQQIEEAARTAEELLTKAKADADELRSTATAESERVR------TEAI 512

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32363191   403 QemqriKATAIRTEEEKRLmEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEarEAERRAKQKLLEIATKPT 476
Cdd:NF041483  513 E-----RATTLRRQAEETL-ERTRAEAERLRAEAEEQAEEVRAAAERAARELRE--ETERAIAARQAEAAEELT 578

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 32363191 212 MYGVNYFTIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKL 291
Cdd:cd13194   1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                        90
                ....*....|....*..
gi 32363191 292 ILQLCIGNHDLFMRRRK 308
Cdd:cd13194  81 ILDLCMGNHELYMRRRK 97

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in merlin and similar proteins; Merlin, also termed moesin-ezrin-radixin-like protein, or neurofibromin-2 (NF2), or Schwannomerlin, or Schwannomin, 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, merlin however lacks the typical actin-binding motif in the C-tail. 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 plays vital roles in controlling proper development of organ sizes by specifically binding to a large number of target proteins localized both in cytoplasm and nuclei. Merlin may function as a tumor suppressor that functions upstream of the core Hippo pathway kinases Lats1/2 (Wts in Drosophila) and Mst1/2 (Hpo in Drosophila), as well as the nuclear E3 ubiquitin ligase DDB1-and-Cullin 4-associated Factor 1 (DCAF1)-associated cullin 4-Roc1 ligase, CRL4(DCAF1). Merlin may also has a tumor suppressor function in melanoma cells, the inhibition of the proto-oncogenic Na(+)/H(+) exchanger isoform 1 (NHE1) activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191  16 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTI-KDTVAWLKMDKKVLDHDVSKEEPVTFHFLA 94
Cdd:cd17186   1 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTIGLRETWYFGLQYTDsKGTVAWLKMDKKVLDQDVPKEEPVTFHFLA 80

                ....*
gi 32363191  95 KFYPE 99
Cdd:cd17186  81 KFYPE 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191   102 EEELVQEITQHLFFLQVKKQILDEKVYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINlyQMTPEMWE 181
Cdd:pfam00373   3 ELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLR--KMKSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 32363191   182 ERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYF 218
Cdd:pfam00373  81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 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 32363191 110 TQHLFFLQVKKQILDEKVYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINlyQMTPEMWEERITAWYA 189
Cdd:cd14473   1 TRYLLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKPKYLSLKRFLPKQLLK--QRKPEEWEKRIVELHK 78

                        90       100
                ....*....|....*....|.
gi 32363191 190 EHRGRARDEAEMEYLKIAQDL 210
Cdd:cd14473  79 KLRGLSPAEAKLKYLKIARKL 99

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Ezrin and similar proteins; Ezrin, also termed cytovillin, or villin-2, or p81, 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 F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Ezrin is a tyrosine kinase substrate that functions as a cross-linker between actin cytoskeleton and plasma membrane. It has been implicated in the regulation of the proliferation, apoptosis, adhesion, invasion, metastasis and angiogenesis of cancer cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191  16 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYT-IKDTVAWLKMDKKVLDHDVSKEEPVTFHFLA 94
Cdd:cd17239   1 KPINVRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREVWYFGLQYVdNKGFPTWLKLDKKVSAQEVRKENPLQFKFRA 80

                ....*
gi 32363191  95 KFYPE 99
Cdd:cd17239  81 KFYPE 85

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 32363191   342 REEAERSRDEPERRVLHMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRL 421
Cdd:pfam20492   1 REEAEREKQELEERLKQYEEETKKAQEELEESEETAEELEEERRQAEEEAERLEQKRQEAEEEKERLEESAEMEAEEKEQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 32363191   422 MEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAE 461
Cdd:pfam20492  81 LEAELAEAQEEIARLEEEVERKEEEARRLQEELEEAREEE 120

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32363191   514 SMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETALDILHSEHSDSGTsSKHNTIKK 575
Cdd:pfam00769   1 SLEIEEERVTYAEKNKRLQEQLKELKSELAQARDETKQTALDILHEENVRQGR-DKYKTLRK 61

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 32363191  18 FTVRIVTMD-AEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVA-WLKMDKKVLDHdVSKEEPVTFHFLAK 95
Cdd:cd01765   1 ISCRVRLLDgTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEDNDGQKhWLDLDKKISKQ-LKRSGPYQFYFRVK 79

                .
gi 32363191  96 F 96
Cdd:cd01765  80 F 80

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191 306 RRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERSRDEPERRVLHMKEEATMANEALMRSEETADLLAEKAQ 385
Cdd:COG1196 275 ELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELE 354

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191 386 ITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAK 465
Cdd:COG1196 355 EAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELE 434

                ....*..
gi 32363191 466 QKLLEIA 472
Cdd:COG1196 435 EEEEEEE 441

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191 305 RRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERSRDEPERRVLHMKEEATMANEALMRSEETADLLAEKA 384
Cdd:COG1196 253 AELEELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEEL 332

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191 385 QITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRA 464
Cdd:COG1196 333 EELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEAL 412

                ....*....
gi 32363191 465 KQKLLEIAT 473
Cdd:COG1196 413 LERLERLEE 421

FERM N-terminal domain; This domain is the N-terminal ubiquitin-like structural domain of the FERM domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 32363191    22 IVTMDA-EMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYT-IKDTVAWLKMDKKVLDHDV 82
Cdd:pfam09379   1 VRLLDGtVLEFDVQPKATGQVLLDQVCNHLNLKEKDYFGLQFLdDNGEHRWLDLSKRLSKQAP 63

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32363191  26 DAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYT-IKDTVAWLKMDKKVLDHdVSKEEPVTFHFLAKFYP 98
Cdd:cd17098  10 DTVHIFQVQQKALGEVLFDQVCKHLNLLESDYFGLEFTdPEGNKCWLDPEKPILRQ-VKRPKDVVFKFVVKFYT 82

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191 306 RRKADSLEVQQMKAQAREEKARKQMERQRLAREKQmREEAERSRDepERRVLHMKEEATMANEALMRSEETADLLAEKAQ 385
Cdd:COG1196 285 EAQAEEYELLAELARLEQDIARLEERRRELEERLE-ELEEELAEL--EEELEELEEELEELEEELEEAEEELEEAEAELA 361

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191 386 ITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAK 465
Cdd:COG1196 362 EAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEE 441

                ....*....
gi 32363191 466 QKLLEIATK 474
Cdd:COG1196 442 EALEEAAEE 450

Ras-associating (RA) domain, FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0/F1 sub-domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting, directly or indirectly, with Ras proteins and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras protein is a small GTPase that is involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon. The FERM 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. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, also known as the N-terminal Ubl-like structural domain of the FERM domain (FERM_N), which is structurally similar to Ub. Some FERM domain-containing proteins contain an N-terminal region, which also has the beta-grasp Ub-like fold, precedes the FERM domain and has been referred to as the F0 domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191  20 VRIVTM-----DAEMEFNCEMKWKGKDLFDLVCRTLGLR-----------ETWFFGLQYTIKDTVA-------------- 69
Cdd:cd01768   2 LKIFGAglasgANYKSVLATARSTARELVAEALERYGLAgspgggpgessCVDAFALCDALGRPAAagvgsgewraehlr 81

                        90       100
                ....*....|....*....|....*....
gi 32363191  70 WLKMDKKV----LDHDVSKEEPVTFHFLA 94
Cdd:cd01768  82 VLGDSERPllvqELWRARPGWARRFELRG 110

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32363191 305 RRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERSRDEPERRVLHMKEEATMANEALMRSEETADLLAEKA 384
Cdd:COG1196 225 LEAELLLLKLRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDI 304