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UniProtKB/Swiss-Prot entry Q8WXG1


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name RSAD2_HUMAN
Primary accession number Q8WXG1
Secondary accession number Q8WVI4
Integrated into Swiss-Prot on November 13, 2007
Sequence was last modified on March 1, 2002 (Sequence version 1)
Annotations were last modified on    June 16, 2009 (Entry version 48)
Name and origin of the protein
Protein name Radical S-adenosyl methionine domain-containing protein 2
Synonyms Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible
Viperin
Cytomegalovirus-induced gene 5 protein
Gene name
Name: RSAD2
Synonyms: CIG5
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
TISSUE=Foreskin fibroblast;
DOI=10.1073/pnas.94.25.13985; PubMed=9391139 [NCBI, ExPASy, EBI, Israel, Japan]
Zhu H., Cong J.-P., Shenk T.;
"Use of differential display analysis to assess the effect of human cytomegalovirus infection on the accumulation of cellular RNAs: induction of interferon-responsive RNAs.";
Proc. Natl. Acad. Sci. U.S.A. 94:13985-13990(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
TISSUE=Macrophage;
DOI=10.1073/pnas.011593298; PubMed=11752458 [NCBI, ExPASy, EBI, Israel, Japan]
Chin K.-C., Cresswell P.;
"Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus.";
Proc. Natl. Acad. Sci. U.S.A. 98:15125-15130(2001).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature03466; PubMed=15815621 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2 and 4.";
Nature 434:724-731(2005).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-42.
TISSUE=Prostate;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
UP-REGULATION IN ATHEROSCLEROSIS.
DOI=10.1161/01.ATV.0000170130.85334.38; PubMed=15890971 [NCBI, ExPASy, EBI, Israel, Japan]
Olofsson P.S., Jatta K., Waagsaeter D., Gredmark S., Hedin U., Paulsson-Berne G., Soederberg-Naucler C., Hansson G.K., Sirsjoe A.;
"The antiviral cytomegalovirus inducible gene 5/viperin is expressed in atherosclerosis and regulated by proinflammatory agents.";
Arterioscler. Thromb. Vasc. Biol. 25:E113-E116(2005).
[7]
FUNCTION, AND INDUCTION.
DOI=10.1002/hep.20844; PubMed=16108059 [NCBI, ExPASy, EBI, Israel, Japan]
Helbig K.J., Lau D.T.-Y., Semendric L., Harley H.A.J., Beard M.R.;
"Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector.";
Hepatology 42:702-710(2005).
[8]
INDUCTION.
DOI=10.1016/j.virol.2005.07.035; PubMed=16150475 [NCBI, ExPASy, EBI, Israel, Japan]
Khaiboullina S.F., Rizvanov A.A., Holbrook M.R., St Jeor S.;
"Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord endothelial cells and induce novel changes in gene expression.";
Virology 342:167-176(2005).
[9]
INDUCTION.
DOI=10.1074/jbc.M604516200; PubMed=16849320 [NCBI, ExPASy, EBI, Israel, Japan]
Severa M., Coccia E.M., Fitzgerald K.A.;
"Toll-like receptor-dependent and -independent viperin gene expression and counter-regulation by PRDI-binding factor-1/BLIMP1.";
J. Biol. Chem. 281:26188-26195(2006).
[10]
FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=16982913 [NCBI, ExPASy, EBI, Israel, Japan]
Rivieccio M.A., Suh H.-S., Zhao Y., Zhao M.-L., Chin K.-C., Lee S.C., Brosnan C.F.;
"TLR3 ligation activates an antiviral response in human fetal astrocytes: a role for viperin/cig5.";
J. Immunol. 177:4735-4741(2006).
[11]
FUNCTION.
DOI=10.1128/JVI.01282-07; PubMed=17686841 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang Y., Burke C.W., Ryman K.D., Klimstra W.B.;
"Identification and characterization of interferon-induced proteins that inhibit alphavirus replication.";
J. Virol. 81:11246-11255(2007).
[12]
INTERACTION WITH FPPS.
DOI=10.1016/j.chom.2007.06.009; PubMed=18005724 [NCBI, ExPASy, EBI, Israel, Japan]
Wang X., Hinson E.R., Cresswell P.;
"The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts.";
Cell Host Microbe 2:96-105(2007).
[13]
FUNCTION.
DOI=10.1016/j.chom.2007.07.005; PubMed=18005719 [NCBI, ExPASy, EBI, Israel, Japan]
Waheed A.A., Freed E.O.;
"Influenza virus not cRAFTy enough to dodge viperin.";
Cell Host Microbe 2:71-72(2007).
Comments
  • FUNCTION: Involved in antiviral defense. May impair virus budding by disrupting lipid rafts at the plasma membrane, a feature which is essential for the budding process of many viruses. Acts through binding with and inactivating FPPS, an enzyme involved in synthesis of cholesterol, farnesylated and geranylated proteins, ubiquinones dolichol and heme. Plays a major role in the cell antiviral state induced by type I and type II interferon. Displays antiviral effect against HIV-1 virus, hepatitis C virus, human cytomegalovirus, and aphaviruses, but not vesiculovirus.
  • COFACTOR: Binds 1 4Fe-4S cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine (By similarity).
  • SUBUNIT: Interacts with FPPS.
  • SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Golgi apparatus. Note=Probably associates with the cytosolic side of the endoplasmic reticulum. Infection with human cytomegalovirus (HCMV) causes relocation to the Golgi apparatus and to cytoplasmic vacuoles which also contain HCMV proteins glycoprotein B and pp28.
  • INDUCTION: By interferon type I, type II and LPS. Little or no induction by interferon gamma is observed in monocytic cell lines. Induced by infection with human cytomegalovirus (HMCV), hepatitis C virus, yellow fever virus and Sendai virus, presumably through type I interferon pathway.
  • MISCELLANEOUS: Up-regulated in atherosclerosis. Latent viruses like HCMV may be involved in atherogenesis by initiating local inflammation. This may induce up-regulation of antiviral gene RSAD2, which modulates lipids synthesis, and thus could play a role in abnormal lipid accumulation leading to atherosclerosis.
  • SIMILARITY: Belongs to the RSAD2 family.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF026941; -; NOT_ANNOTATED_CDS; mRNA.[EMBL / GenBank / DDBJ]
AF442151; AAL50053.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC017076; AAY14802.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CH471053; EAX01034.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC017969; AAH17969.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00291463; -.
RefSeq NP_542388.2; -.
UniGene Hs.17518
3D structure databases
ModBase Q8WXG1.
Organism-specific databases
GeneCards GC02P006969; -.
HGNC HGNC:30908; RSAD2.
GenAtlas RSAD2.
MIM 607810; gene. [NCBI / EBI]
PharmGKB PA134937442; -.
Gene expression databases
ArrayExpress Q8WXG1; -.
Bgee Q8WXG1; -.
CleanEx HS_RSAD2; -.
Ontologies
GO
GO:0005789; Cellular component: endoplasmic reticulum membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005794; Cellular component: Golgi apparatus (inferred from electronic annotation from UniProtKB-SubCell).
GO:0003824; Molecular function: catalytic activity (inferred from electronic annotation from InterPro).
GO:0005506; Molecular function: iron ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0051536; Molecular function: iron-sulfur cluster binding (inferred from electronic annotation from UniProtKB-KW).
GO:0051607; Biological process: defense response to virus (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR006638; Elp3/MiaB/NifB.
IPR007197; Radical_SAM.
Graphical view of domain structure.
Pfam PF04055; Radical_SAM; 1.
Pfam graphical view of domain structure.
SMART SM00729; Elp3; 1.
SMART graphical view of domain structure.
Proteomic databases
PRIDE Q8WXG1; -.
Genome annotation databases
Ensembl ENSG00000134321; Homo sapiens. [Contig view]
GeneID 91543; -.
KEGG hsa:91543; -.
NMPDR fig|9606.3.peg.17475; -.
Phylogenomic databases
HOVERGEN Q8WXG1; -.
OMA Q8WXG1; LQKLRTW.
Other
NextBio 77284; -.
SOURCE RSAD2; Homo sapiens.
ProtoNet Q8WXG1.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Antiviral defense; Atherosclerosis; Endoplasmic reticulum; Golgi apparatus; Iron; Iron-sulfur; Membrane; Metal-binding; Polymorphism; S-adenosyl-L-methionine.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
CHAIN   1   361  361     Radical S-adenosyl methionine domain-containing protein 2. PRO_0000309583
METAL   83    83        Iron-sulfur (4Fe-4S-S-AdoMet) (Potential). 
METAL   87    87        Iron-sulfur (4Fe-4S-S-AdoMet) (Potential). 
METAL   90    90        Iron-sulfur (4Fe-4S-S-AdoMet) (Potential). 
VARIANT   42    42  1     L -> R (in dbSNP:rs17851586 [NCBI]). VAR_036980 
VARIANT   52    52  1     V -> I (in dbSNP:rs2305257 [NCBI]). VAR_053974 
CONFLICT   13    13        L -> F (in Ref. 1; AF026941). 
CONFLICT   216   217        VA -> IP (in Ref. 1; AF026941). 
Sequence information
Length: 361 AA [This is the length of the unprocessed precursor] Molecular weight: 42170 Da [This is the MW of the unprocessed precursor] CRC64: ED014743CE1568DF [This is a checksum on the sequence]
        10         20         30         40         50         60 
MWVLTPAAFA GKLLSVFRQP LSSLWRSLVP LFCWLRATFW LLATKRRKQQ LVLRGPDETK 

        70         80         90        100        110        120 
EEEEDPPLPT TPTSVNYHFT RQCNYKCGFC FHTAKTSFVL PLEEAKRGLL LLKEAGMEKI 

       130        140        150        160        170        180 
NFSGGEPFLQ DRGEYLGKLV RFCKVELRLP SVSIVSNGSL IRERWFQNYG EYLDILAISC 

       190        200        210        220        230        240 
DSFDEEVNVL IGRGQGKKNH VENLQKLRRW CRDYRVAFKI NSVINRFNVE EDMTEQIKAL 

       250        260        270        280        290        300 
NPVRWKVFQC LLIEGENCGE DALREAERFV IGDEEFERFL ERHKEVSCLV PESNQKMKDS 

       310        320        330        340        350        360 
YLILDEYMRF LNCRKGRKDP SKSILDVGVE EAIKFSGFDE KMFLKRGGKY IWSKADLKLD 


W 

Q8WXG1 in FASTA format

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