{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P0DSV7","secondaryAccessions":["P34015","Q85407","Q89098","Q89118"],"uniProtkbId":"CRMB_VAR67","entryAudit":{"firstPublicDate":"2019-10-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2019-10-16","entryVersion":23,"sequenceVersion":1},"annotationScore":4.0,"organism":{"scientificName":"Variola virus (isolate Human/India/Ind3/1967)","commonName":"VARV","synonyms":["Smallpox virus"],"taxonId":587200,"lineage":["Viruses","Varidnaviria","Bamfordvirae","Nucleocytoviricota","Pokkesviricetes","Chitovirales","Poxviridae","Chordopoxvirinae","Orthopoxvirus","Orthopoxvirus variola","Variola virus"]},"organismHosts":[{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606}],"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Cytokine response-modifying protein B"},"shortNames":[{"value":"CrmB"}]},"alternativeNames":[{"fullName":{"value":"Viral tumor necrosis factor receptor II"},"shortNames":[{"value":"vTNFR"}]}],"flag":"Precursor"},"genes":[{"geneName":{"value":"OPG002"},"orfNames":[{"value":"G2R"},{"value":"G4R"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16581912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17070121"}],"value":"Inhibits host immune defense by binding to host TNF and various chemokines in the extracellular space (PubMed:16581912, PubMed:17070121). Binds host CC chemokines (beta chemokines) and CXC chemokines (alpha chemokines) (PubMed:16581912)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16581912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19961417"}],"value":"Homodimer (PubMed:19961417). Interacts with host TNF, LTA, CCL28, CCL25, CXCL12, CXCL13 and CXCl14 (PubMed:16581912)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O73559"}],"value":"Secreted","id":"SL-0243"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q76ZJ3"}],"value":"Expressed in the early phase of the viral replicative cycle"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20979600"}],"value":"The N-terminal region is similar to host TNF receptor 2/TNFRSF1B and binds host TNF. The C-terminal region is called smallpox virus-encoded chemokine receptor (SECRET), and binds host cytokines (PubMed:20979600)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the orthopoxvirus OPG002 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":22,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Chain","location":{"start":{"value":23,"modifier":"EXACT"},"end":{"value":349,"modifier":"EXACT"}},"description":"Cytokine response-modifying protein B","featureId":"PRO_0000034615"},{"type":"Repeat","location":{"start":{"value":31,"modifier":"EXACT"},"end":{"value":66,"modifier":"EXACT"}},"description":"TNFR-Cys 1"},{"type":"Repeat","location":{"start":{"value":67,"modifier":"EXACT"},"end":{"value":108,"modifier":"EXACT"}},"description":"TNFR-Cys 2"},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":160,"modifier":"EXACT"}},"description":"TNF-binding"},{"type":"Region","location":{"start":{"value":161,"modifier":"EXACT"},"end":{"value":349,"modifier":"EXACT"}},"description":"Chemokine-binding"},{"type":"Glycosylation","location":{"start":{"value":101,"modifier":"EXACT"},"end":{"value":101,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine; by host","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":173,"modifier":"EXACT"},"end":{"value":173,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine; by host","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":189,"modifier":"EXACT"},"end":{"value":189,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine; by host","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":215,"modifier":"EXACT"},"end":{"value":215,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine; by host","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":248,"modifier":"EXACT"},"end":{"value":248,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine; by host","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":""},{"type":"Disulfide bond","location":{"start":{"value":32,"modifier":"EXACT"},"end":{"value":43,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00206"}]},{"type":"Disulfide bond","location":{"start":{"value":44,"modifier":"EXACT"},"end":{"value":57,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00206"}]},{"type":"Disulfide bond","location":{"start":{"value":47,"modifier":"EXACT"},"end":{"value":65,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00206"}]},{"type":"Disulfide bond","location":{"start":{"value":68,"modifier":"EXACT"},"end":{"value":83,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00206"}]},{"type":"Disulfide bond","location":{"start":{"value":86,"modifier":"EXACT"},"end":{"value":100,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00206"}]},{"type":"Disulfide bond","location":{"start":{"value":90,"modifier":"EXACT"},"end":{"value":108,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00206"}]}],"keywords":[{"id":"KW-1015","category":"PTM","name":"Disulfide bond"},{"id":"KW-0325","category":"PTM","name":"Glycoprotein"},{"id":"KW-0945","category":"Biological process","name":"Host-virus interaction"},{"id":"KW-1086","category":"Biological process","name":"Inhibition of host chemokines by virus"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0677","category":"Domain","name":"Repeat"},{"id":"KW-0964","category":"Cellular component","name":"Secreted"},{"id":"KW-0732","category":"Domain","name":"Signal"},{"id":"KW-0899","category":"Biological process","name":"Viral immunoevasion"}],"references":[{"referenceNumber":1,"citation":{"id":"8384129","citationType":"journal article","authors":["Shchelkunov S.N.","Blinov V.M.","Sandakhchiev L.S."],"citationCrossReferences":[{"database":"PubMed","id":"8384129"},{"database":"DOI","id":"10.1016/0014-5793(93)80041-r"}],"title":"Genes of variola and vaccinia viruses necessary to overcome the host protective mechanisms.","publicationDate":"1993","journal":"FEBS Lett.","firstPage":"80","lastPage":"83","volume":"319"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]"]},{"referenceNumber":2,"citation":{"id":"16581912","citationType":"journal article","authors":["Alejo A.","Ruiz-Arguello M.B.","Ho Y.","Smith V.P.","Saraiva M.","Alcami A."],"citationCrossReferences":[{"database":"PubMed","id":"16581912"},{"database":"DOI","id":"10.1073/pnas.0510462103"}],"title":"A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.","publicationDate":"2006","journal":"Proc. Natl. Acad. Sci. U.S.A.","firstPage":"5995","lastPage":"6000","volume":"103"},"referencePositions":["FUNCTION","INTERACTION WITH HOST TNF; LTA; CCL28; CCL25; CXCL12; CXCL13 AND CXCL14"]},{"referenceNumber":3,"citation":{"id":"17070121","citationType":"journal article","authors":["Gileva I.P.","Nepomnyashchikh T.S.","Antonets D.V.","Lebedev L.R.","Kochneva G.V.","Grazhdantseva A.V.","Shchelkunov S.N."],"citationCrossReferences":[{"database":"PubMed","id":"17070121"},{"database":"DOI","id":"10.1016/j.bbapap.2006.09.006"}],"title":"Properties of the recombinant TNF-binding proteins from variola, monkeypox, and cowpox viruses are different.","publicationDate":"2006","journal":"Biochim. Biophys. Acta","firstPage":"1710","lastPage":"1718","volume":"1764"},"referencePositions":["FUNCTION"]},{"referenceNumber":4,"citation":{"id":"19961417","citationType":"journal article","authors":["Gileva I.P.","Nepomnyashchikh T.S.","Ryazankin I.A.","Shchelkunov S.N."],"citationCrossReferences":[{"database":"PubMed","id":"19961417"},{"database":"DOI","id":"10.1134/s0006297909120098"}],"title":"Recombinant TNF-binding protein from variola virus as a novel potential TNF antagonist.","publicationDate":"2009","journal":"Biochemistry (Mosc.)","firstPage":"1356","lastPage":"1362","volume":"74"},"referencePositions":["SUBUNIT"]},{"referenceNumber":5,"citation":{"id":"20979600","citationType":"journal article","authors":["Antonets D.V.","Nepomnyashchikh T.S.","Shchelkunov S.N."],"citationCrossReferences":[{"database":"PubMed","id":"20979600"},{"database":"DOI","id":"10.1186/1756-0500-3-271"}],"title":"SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family.","publicationDate":"2010","journal":"BMC Res. Notes","firstPage":"271","lastPage":"271","volume":"3"},"referencePositions":["DOMAIN"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"X69198","properties":[{"key":"ProteinId","value":"CAA49137.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"X67117","properties":[{"key":"ProteinId","value":"CAA47540.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"PIR","id":"D36858","properties":[{"key":"EntryName","value":"D36858"}]},{"database":"RefSeq","id":"NP_042240.1","properties":[{"key":"NucleotideSequenceId","value":"NC_001611.1"}]},{"database":"AlphaFoldDB","id":"P0DSV7","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"P0DSV7","properties":[{"key":"Description","value":"-"}]},{"database":"DIP","id":"DIP-61146N","properties":[{"key":"Description","value":"-"}]},{"database":"IntAct","id":"P0DSV7","properties":[{"key":"Interactions","value":"11"}]},{"database":"GlyCosmos","id":"P0DSV7","properties":[{"key":"glycosylation","value":"5 sites, No reported glycans"}]},{"database":"GeneID","id":"1486427","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"vg:1486427","properties":[{"key":"Description","value":"-"}]},{"database":"Proteomes","id":"UP000002060","properties":[{"key":"Component","value":"Segment"}]},{"database":"GO","id":"GO:0005576","properties":[{"key":"GoTerm","value":"C:extracellular region"},{"key":"GoEvidenceType","value":"IDA:UniProt"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"16581912"}]},{"database":"GO","id":"GO:0005031","properties":[{"key":"GoTerm","value":"F:tumor necrosis factor receptor activity"},{"key":"GoEvidenceType","value":"IDA:UniProt"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"16581912"}]},{"database":"GO","id":"GO:0052031","properties":[{"key":"GoTerm","value":"P:symbiont-mediated perturbation of host defense response"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-KW"}]},{"database":"CDD","id":"cd15839","properties":[{"key":"EntryName","value":"TNFRSF_viral"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"2.60.240.20","properties":[{"key":"EntryName","value":"-"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"2.10.50.10","properties":[{"key":"EntryName","value":"Tumor Necrosis Factor Receptor, subunit A, domain 2"},{"key":"MatchStatus","value":"2"}]},{"database":"InterPro","id":"IPR010806","properties":[{"key":"EntryName","value":"Poxvirus_TNF-rcpt-II_C"}]},{"database":"InterPro","id":"IPR011172","properties":[{"key":"EntryName","value":"Poxvirus_TNF_rcpt-II"}]},{"database":"InterPro","id":"IPR051670","properties":[{"key":"EntryName","value":"TNF_chemokine_rcpt-like"}]},{"database":"InterPro","id":"IPR001368","properties":[{"key":"EntryName","value":"TNFR/NGFR_Cys_rich_reg"}]},{"database":"InterPro","id":"IPR034059","properties":[{"key":"EntryName","value":"TNFRSF_N_viral"}]},{"database":"PANTHER","id":"PTHR47386","properties":[{"key":"EntryName","value":"TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 1B"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR47386:SF1","properties":[{"key":"EntryName","value":"TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 1B"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF07190","properties":[{"key":"EntryName","value":"CrmD_SECRET"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF00020","properties":[{"key":"EntryName","value":"TNFR_c6"},{"key":"MatchStatus","value":"1"}]},{"database":"PIRSF","id":"PIRSF001790","properties":[{"key":"EntryName","value":"TNF_C22L"},{"key":"MatchStatus","value":"1"}]},{"database":"SMART","id":"SM00208","properties":[{"key":"EntryName","value":"TNFR"},{"key":"MatchStatus","value":"3"}]},{"database":"SUPFAM","id":"SSF57586","properties":[{"key":"EntryName","value":"TNF receptor-like"},{"key":"MatchStatus","value":"2"}]},{"database":"PROSITE","id":"PS00652","properties":[{"key":"EntryName","value":"TNFR_NGFR_1"},{"key":"MatchStatus","value":"2"}]},{"database":"PROSITE","id":"PS50050","properties":[{"key":"EntryName","value":"TNFR_NGFR_2"},{"key":"MatchStatus","value":"2"}]}],"sequence":{"value":"MKSVLYLYILFLSCIIINGRDAAPYTPPNGKCKDTEYKRHNLCCLSCPPGTYASRLCDSKTNTQCTPCGSGTFTSRNNHLPACLSCNGRCNSNQVETRSCNTTHNRICECSPGYYCLLKGSSGCKACVSQTKCGIGYGVSGHTSVGDVICSPCGFGTYSHTVSSADKCEPVPNNTFNYIDVEITLYPVNDTSCTRTTTTGLSESILTSELTITMNHTDCNPVFREEYFSVLNKVATSGFFTGENRYQNISKVCTLNFEIKCNNKGSSFKQLTKAKNDDGMMSHSETVTLAGDCLSSVDIYILYSNTNAQDYETDTISYRVGNVLDDDSHMPGSCNIHKPITNSKPTRFL","length":349,"molWeight":38189,"crc64":"D45D40B5C6E780EF","md5":"41B72D3652D32DF7E9652A3D9965888C"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"SUBUNIT":1,"SUBCELLULAR LOCATION":1,"INDUCTION":1,"DOMAIN":1,"SIMILARITY":1},"countByFeatureType":{"Signal":1,"Chain":1,"Repeat":2,"Region":2,"Glycosylation":5,"Disulfide bond":6},"uniParcId":"UPI0000128460"}}