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 14133887 216 MYGVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKL 295
Cdd:cd13194   1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                        90
                ....*....|....*..
gi 14133887 296 ILQLCIGNHDLFMRRRK 312
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 14133887   346 REEAERTRDELERRLLQMKEEATMANEALMRSEETADLLAEKAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRL 425
Cdd:pfam20492   1 REEAEREKQELEERLKQYEEETKKAQEELEESEETAEELEEERRQAEEEAERLEQKRQEAEEEKERLEESAEMEAEEKEQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 14133887   426 MEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAE 465
Cdd:pfam20492  81 LEAELAEAQEEIARLEEEVERKEEEARRLQEELEEAREEE 120

PRLI-interacting factor K; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14133887  307 FMRRRKADSLEvqqmkaqaREEKARKQMERQRLAREKQMREEAERTRDELE-----RRL--LQMKEEA 367
Cdd:PLN03086   3 FELRRAREKLE--------REQRERKQRAKLKLERERKAKEEAAKQREAIEaaqrsRRLdaIEAQIKA 62

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 14133887 216 MYGVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKL 295
Cdd:cd13194   1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                        90
                ....*....|....*..
gi 14133887 296 ILQLCIGNHDLFMRRRK 312
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 14133887  20 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTI-KDTVAWLKMDKKVLDHDVSKEEPVTFHFLA 98
Cdd:cd17186   1 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTIGLRETWYFGLQYTDsKGTVAWLKMDKKVLDQDVPKEEPVTFHFLA 80

                ....*
gi 14133887  99 KFYPE 103
Cdd:cd17186  81 KFYPE 85

FERM C-terminal PH-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887   226 NKKGTELLLGVDALGLHIYDPENRLtpKISFPWNEIRNISYSDKEFTIKPLDKKI-DVFKFNSSKLRVNKLILQLCIGNH 304
Cdd:pfam09380   1 DKEGTDLWLGVSAKGILVYEDNNKI--LNLFPWREIRKISFKRKKFLIKLRDKSSeETLGFYTESSRACKYLWKLCVEQH 78

                  ....*..
gi 14133887   305 DLFMRRR 311
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 14133887   518 SMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETALDILHNENSdRGGSSKHNTIKK 579
Cdd:pfam00769   1 SLEIEEERVTYAEKNKRLQEQLKELKSELAQARDETKQTALDILHEENV-RQGRDKYKTLRK 61

cell envelope integrity inner membrane protein TolA; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887  319 QQMKAQAREEKARKQMERQRlAREKQMREEAERTR-DELERRLLQMKEEATMAnealmrsEETADLLAEKAQITEEEAKL 397
Cdd:PRK09510  69 QQQKSAKRAEEQRKKKEQQQ-AEELQQKQAAEQERlKQLEKERLAAQEQKKQA-------EEAAKQAALKQKQAEEAAAK 140

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887  398 LAQKA-AEAEQEMQRIKATAIRTEEEKrlmeqKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIA 476
Cdd:PRK09510 141 AAAAAkAKAEAEAKRAAAAAKKAAAEA-----KKKAEAEAAKKAAAEAKKKAEAEAAAKAAAEAKKKAEAEAKKKAAAEA 215

                 ..
gi 14133887  477 TK 478
Cdd:PRK09510 216 KK 217

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887   310 RRKADSLEVQQMKAQAREEkARKQMERQRLAREKQMREEAERTRDELERRllqmKEEATMANEALMRSEEtADLLAEKAQ 389
Cdd:PTZ00121 1430 KKKADEAKKKAEEAKKADE-AKKKAEEAKKAEEAKKKAEEAKKADEAKKK----AEEAKKADEAKKKAEE-AKKKADEAK 1503

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887   390 ITEEEAKLL--------AQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEA 461
Cdd:PTZ00121 1504 KAAEAKKKAdeakkaeeAKKADEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKA 1583

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887   462 REAERRAKQKLLEIAtkPTYPPMNPIPAPLPPDIPSFNLIGDSLSfdfKDTDMKRLSMEIEKEKVEYMEKSKHLQEQLNE 541
Cdd:PTZ00121 1584 EEAKKAEEARIEEVM--KLYEEEKKMKAEEAKKAEEAKIKAEELK---KAEEEKKKVEQLKKKEAEEKKKAEELKKAEEE 1658

                         250
                  ....*....|....
gi 14133887   542 LKTEIEALKLKERE 555
Cdd:PTZ00121 1659 NKIKAAEEAKKAEE 1672

polarized growth protein Scy;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887   312 KADSLEVQQmKAQAREEKARKQMERQRLAREKQMREEAERTRDELERrllQMKEEATMANEALMRSEETAdllaekAQIT 391
Cdd:NF041483  490 KADADELRS-TATAESERVRTEAIERATTLRRQAEETLERTRAEAER---LRAEAEEQAEEVRAAAERAA------RELR 559

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887   392 EEEAKLLAQKAAEAEQEMQRikataIRTEEEKRLM--EQKV----LEAEVLALKMAEESERRAKEADQLKQDLQEAREAE 465
Cdd:NF041483  560 EETERAIAARQAEAAEELTR-----LHTEAEERLTaaEEALadarAEAERIRREAAEETERLRTEAAERIRTLQAQAEQE 634

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 307 FMRRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEETADLLAE 386
Cdd:COG1196 565 YLKAAKAGRATFLPLDKIRARAALAAALARGAIGAAVDLVASDLREADARYYVLGDTLLGRTLVAARLEAALRRAVTLAG 644

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 387 KAQITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAE---VLALKMAEESERRAKEADQLKQDLQEARE 463
Cdd:COG1196 645 RLREVTLEGEGGSAGGSLTGGSRRELLAALLEAEAELEELAERLAEEElelEEALLAEEEEERELAEAEEERLEEELEEE 724

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 464 AERRAKQKLLEIATKPTYPPMNPIPAPLPPDIPsfnligDSLSFDFKDTDMKRLSMEIEK-EKV------EY---MEKSK 533
Cdd:COG1196 725 ALEEQLEAEREELLEELLEEEELLEEEALEELP------EPPDLEELERELERLEREIEAlGPVnllaieEYeelEERYD 798

                       250
                ....*....|....*.
gi 14133887 534 HLQEQLNELKTEIEAL 549
Cdd:COG1196 799 FLSEQREDLEEARETL 814

F-type ATP synthase, membrane subunit b; Membrane subunit b is a component of the Fo complex of FoF1-ATP synthase. The F-type ATP synthases (FoF1-ATPase) consist of two structural domains: the F1 (assembly factor one) complex containing the soluble catalytic core, and the Fo (oligomycin sensitive factor) complex containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. F1 is composed of alpha (or A), beta (B), gamma (C), delta (D) and epsilon (E) subunits with a stoichiometry of 3:3:1:1:1, while Fo consists of the three subunits a, b, and c (1:2:10-14). An oligomeric ring of 10-14 c subunits (c-ring) make up the Fo rotor. The flux of protons through the ATPase channel (Fo) drives the rotation of the c-ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the c-ring of Fo. The F-ATP synthases are primarily found in the inner membranes of eukaryotic mitochondria, in the thylakoid membranes of chloroplasts or in the plasma membranes of bacteria. The F-ATP synthases are the primary producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts). Alternatively, under conditions of low driving force, ATP synthases function as ATPases, thus generating a transmembrane proton or Na(+) gradient at the expense of energy derived from ATP hydrolysis. This group also includes F-ATP synthase that has also been found in the archaea Candidatus Methanoperedens.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 329 KARKQMERQRLAREKQMREEAERTRDELERRLLQMKEEA-TMANEALMRSEETADLLAEKAQitEEEAKLLAQKAAEAEQ 407
Cdd:cd06503  29 DEREEKIAESLEEAEKAKEEAEELLAEYEEKLAEARAEAqEIIEEARKEAEKIKEEILAEAK--EEAERILEQAKAEIEQ 106

                        90
                ....*....|...
gi 14133887 408 EMQRIKAtAIRTE 420
Cdd:cd06503 107 EKEKALA-ELRKE 118

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 14133887  305 DLFMRRRKADSLEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEETADLL 384
Cdd:NF033838 189 ELELVKEEAKEPRDEEKIKQAKAKVESKKAEATRLEKIKTDREKAEEEAKRRADAKLKEAVEKNVATSEQDKPKRRAKRG 268

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887  385 AEKAQIT----EEEAKLLA----------------QKAAEAEQEMQRIKATAIRTEEEKRL----------------MEQ 428
Cdd:NF033838 269 VLGEPATpdkkENDAKSSDssvgeetlpspslkpeKKVAEAEKKVEEAKKKAKDQKEEDRRnyptntyktleleiaeSDV 348

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887  429 KVLEAEVLALK--------------MAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIATKPTYPPMNPIPAPLP-P 493
Cdd:NF033838 349 KVKEAELELVKeeakeprneekikqAKAKVESKKAEATRLEKIKTDRKKAEEEAKRKAAEEDKVKEKPAEQPQPAPAPqP 428

                 ....
gi 14133887  494 DIPS 497
Cdd:NF033838 429 EKPA 432

polarized growth protein Scy;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887   319 QQMKAQArEEKARKQMERQRLAREKQM---REEAERTRDELERRLLQMKEEATMANEALM-RSEETADLLAEKAQITEEE 394
Cdd:NF041483  155 EQLRART-ESQARRLLDESRAEAEQALaaaRAEAERLAEEARQRLGSEAESARAEAEAILrRARKDAERLLNAASTQAQE 233

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 14133887   395 A-----KLLAQKAAEAEQEMQrikataiRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEA 451
Cdd:NF041483  234 AtdhaeQLRSSTAAESDQARR-------QAAELSRAAEQRMQEAEEALREARAEAEKVVAEA 288

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 14133887 216 MYGVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKKIDVFKFNSSKLRVNKL 295
Cdd:cd13194   1 MYGVNYFEIKNKKGTDLWLGVDALGLNIYEPDNKLTPKIGFPWSEIRNISFNDKKFVIKPIDKKAPDFVFYSPRLRINKR 80

                        90
                ....*....|....*..
gi 14133887 296 ILQLCIGNHDLFMRRRK 312
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 14133887  20 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTI-KDTVAWLKMDKKVLDHDVSKEEPVTFHFLA 98
Cdd:cd17186   1 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTIGLRETWYFGLQYTDsKGTVAWLKMDKKVLDQDVPKEEPVTFHFLA 80

                ....*
gi 14133887  99 KFYPE 103
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 14133887   106 EEELVQEITQHLFFLQVKKQILDEKIYCPPEASVLLASYAVQAKYGDYDPSVHKRGFLAQEELLPKRVINlyQMTPEMWE 185
Cdd:pfam00373   3 ELLLQDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDYQPSSHTSEYLSLESFLPKQLLR--KMKSKELE 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 14133887   186 ERITAWYAEHRGRARDEAEMEYLKIAQDLEMYGVNYF 222
Cdd:pfam00373  81 KRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in the ERM family proteins, Ezrin, Radixin, and Moesin; The ezrin-radixin-moesin (ERM) family includes a group of closely related 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. 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).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887  23 TVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYT-IKDTVAWLKMDKKVLDHDVSKEEPVTFHFLAKFY 101
Cdd:cd17187   2 NVRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREIWFFGLQYVdSKGYSTWLKLNKKVLSQDVKKENPLQFKFRAKFY 81

                ..
gi 14133887 102 PE 103
Cdd:cd17187  82 PE 83

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 14133887  20 KTFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYT-IKDTVAWLKMDKKVLDHDVSKEEPVTFHFLA 98
Cdd:cd17239   1 KPINVRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREVWYFGLQYVdNKGFPTWLKLDKKVSAQEVRKENPLQFKFRA 80

                ....*
gi 14133887  99 KFYPE 103
Cdd:cd17239  81 KFYPE 85

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in moesin and similar proteins; Moesin, also termed membrane-organizing extension spike protein, 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). Moesin is involved in mitotic spindle function through stabilizing cell shape and microtubules at the cell cortex. It is required for the formation of F-actin networks that mediate endosome biogenesis or maturation and transport through the degradative pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887  21 TFTVRIVTMDAEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYtiKDTVA---WLKMDKKVLDHDVSKEEPVTFHFL 97
Cdd:cd17237   1 TISVRVTTMDAELEFAIQPNTTGKQLFDQVVKTIGLREVWFFGLQY--QDTKGfstWLKLNKKVTAQDVRKESPLLFKFR 78

                ....*.
gi 14133887  98 AKFYPE 103
Cdd:cd17237  79 AKFYPE 84

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 14133887   518 SMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETALDILHNENSdRGGSSKHNTIKK 579
Cdd:pfam00769   1 SLEIEEERVTYAEKNKRLQEQLKELKSELAQARDETKQTALDILHEENV-RQGRDKYKTLRK 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 14133887  22 FTVRIVTMD-AEMEFNCEMKWKGKDLFDLVCRTLGLRETWFFGLQYTIKDTVA-WLKMDKKVLDHdVSKEEPVTFHFLAK 99
Cdd:cd01765   1 ISCRVRLLDgTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEDNDGQKhWLDLDKKISKQ-LKRSGPYQFYFRVK 79

                .
gi 14133887 100 F 100
Cdd:cd01765  80 F 80

FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B); FRMD4A is part of the Par-3/FRMD4A/cytohesin-1 complex that activates Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodeling and epithelial polarization. The Par-3/Par-6/aPKC/Cdc42 complex regulates the conversion of primordial adherens junctions (AJs) into belt-like AJs and the formation of linear actin cables. When primordial AJs are formed, Par-3 recruits scaffolding protein FRMD4A which connects Par-3 and the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-1. FRMD4B (also called GRP1-binding protein, GRSP1) is a novel member of GRP1 signaling complexes that are recruited to plasma membrane ruffles in response to insulin receptor signaling. The GRSP1/FRMD4B protein contains a FERM protein domain as well as two coiled coil domains and may function as a scaffolding protein. GRP1 and GRSP1 interact through the coiled coil domains in the two proteins. 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 14133887 218 GVNYFAIRNKKGTELLLGVDALGLHIYDPENRLTPKISFPWNEIRNISYSDKEFTIKPLDKK--------------IDVF 283
Cdd:cd13191   1 GVHYYEVKDKNGIPWWLGVSYKGIGQYDLQDKVKPRKFFQWKQLENLYFRDRKFSIEVRDPRrnshrsrrtfqsssVSVH 80

                        90       100       110
                ....*....|....*....|....*....|
gi 14133887 284 KFNSSKLRVNKLILQLCIGNHDLFMRRRKA 313
Cdd:cd13191  81 VWYGQTPALCKTIWSMAIAQHQFYLDRKQS 110

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 317 EVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEETADLLAEKAQITEEEAK 396
Cdd:COG1196 240 ELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLE 319

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 397 LLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEIA 476
Cdd:COG1196 320 ELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELA 399

                ..
gi 14133887 477 TK 478
Cdd:COG1196 400 AQ 401

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 316 LEVQQMKAQAREEKARKQMERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEETADLLAEKAQITEEEA 395
Cdd:COG1196 274 LELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEEL 353

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 396 KLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAKQKLLEI 475
Cdd:COG1196 354 EEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAEL 433

                ...
gi 14133887 476 ATK 478
Cdd:COG1196 434 EEE 436

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 310 RRKADSLEVQQMKAQAREEKARKQMERQRLAREKQmREEAErtRDELERRLLQMKEEATMANEALMRSEETADLLAEKAQ 389
Cdd:COG1196 285 EAQAEEYELLAELARLEQDIARLEERRRELEERLE-ELEEE--LAELEEELEELEEELEELEEELEEAEEELEEAEAELA 361

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14133887 390 ITEEEAKLLAQKAAEAEQEMQRIKATAIRTEEEKRLMEQKVLEAEVLALKMAEESERRAKEADQLKQDLQEAREAERRAK 469
Cdd:COG1196 362 EAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEE 441