ID   RSAD2_HUMAN             Reviewed;         361 AA.
AC   Q8WXG1; Q8WVI4;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   03-NOV-2009, entry version 54.
DE   RecName: Full=Radical S-adenosyl methionine domain-containing protein 2;
DE   AltName: Full=Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible;
DE            Short=Viperin;
DE   AltName: Full=Cytomegalovirus-induced gene 5 protein;
GN   Name=RSAD2; Synonyms=CIG5;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC   TISSUE=Foreskin fibroblast;
RX   MEDLINE=98054347; PubMed=9391139; DOI=10.1073/pnas.94.25.13985;
RA   Zhu H., Cong J.-P., Shenk T.;
RT   "Use of differential display analysis to assess the effect of human
RT   cytomegalovirus infection on the accumulation of cellular RNAs:
RT   induction of interferon-responsive RNAs.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:13985-13990(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP   INDUCTION.
RC   TISSUE=Macrophage;
RX   MEDLINE=21625108; PubMed=11752458; DOI=10.1073/pnas.011593298;
RA   Chin K.-C., Cresswell P.;
RT   "Viperin (cig5), an IFN-inducible antiviral protein directly induced
RT   by human cytomegalovirus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:15125-15130(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-42.
RC   TISSUE=Prostate;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   UP-REGULATION IN ATHEROSCLEROSIS.
RX   PubMed=15890971; DOI=10.1161/01.ATV.0000170130.85334.38;
RA   Olofsson P.S., Jatta K., Waagsaeter D., Gredmark S., Hedin U.,
RA   Paulsson-Berne G., Soederberg-Naucler C., Hansson G.K., Sirsjoe A.;
RT   "The antiviral cytomegalovirus inducible gene 5/viperin is expressed
RT   in atherosclerosis and regulated by proinflammatory agents.";
RL   Arterioscler. Thromb. Vasc. Biol. 25:E113-E116(2005).
RN   [7]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=16108059; DOI=10.1002/hep.20844;
RA   Helbig K.J., Lau D.T.-Y., Semendric L., Harley H.A.J., Beard M.R.;
RT   "Analysis of ISG expression in chronic hepatitis C identifies viperin
RT   as a potential antiviral effector.";
RL   Hepatology 42:702-710(2005).
RN   [8]
RP   INDUCTION.
RX   PubMed=16150475; DOI=10.1016/j.virol.2005.07.035;
RA   Khaiboullina S.F., Rizvanov A.A., Holbrook M.R., St Jeor S.;
RT   "Yellow fever virus strains Asibi and 17D-204 infect human umbilical
RT   cord endothelial cells and induce novel changes in gene expression.";
RL   Virology 342:167-176(2005).
RN   [9]
RP   INDUCTION.
RX   PubMed=16849320; DOI=10.1074/jbc.M604516200;
RA   Severa M., Coccia E.M., Fitzgerald K.A.;
RT   "Toll-like receptor-dependent and -independent viperin gene expression
RT   and counter-regulation by PRDI-binding factor-1/BLIMP1.";
RL   J. Biol. Chem. 281:26188-26195(2006).
RN   [10]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=16982913;
RA   Rivieccio M.A., Suh H.-S., Zhao Y., Zhao M.-L., Chin K.-C., Lee S.C.,
RA   Brosnan C.F.;
RT   "TLR3 ligation activates an antiviral response in human fetal
RT   astrocytes: a role for viperin/cig5.";
RL   J. Immunol. 177:4735-4741(2006).
RN   [11]
RP   FUNCTION.
RX   PubMed=17686841; DOI=10.1128/JVI.01282-07;
RA   Zhang Y., Burke C.W., Ryman K.D., Klimstra W.B.;
RT   "Identification and characterization of interferon-induced proteins
RT   that inhibit alphavirus replication.";
RL   J. Virol. 81:11246-11255(2007).
RN   [12]
RP   INTERACTION WITH FPPS.
RX   PubMed=18005724; DOI=10.1016/j.chom.2007.06.009;
RA   Wang X., Hinson E.R., Cresswell P.;
RT   "The interferon-inducible protein viperin inhibits influenza virus
RT   release by perturbing lipid rafts.";
RL   Cell Host Microbe 2:96-105(2007).
RN   [13]
RP   FUNCTION.
RX   PubMed=18005719; DOI=10.1016/j.chom.2007.07.005;
RA   Waheed A.A., Freed E.O.;
RT   "Influenza virus not cRAFTy enough to dodge viperin.";
RL   Cell Host Microbe 2:71-72(2007).
CC   -!- FUNCTION: Involved in antiviral defense. May impair virus budding
CC       by disrupting lipid rafts at the plasma membrane, a feature which
CC       is essential for the budding process of many viruses. Acts through
CC       binding with and inactivating FPPS, an enzyme involved in
CC       synthesis of cholesterol, farnesylated and geranylated proteins,
CC       ubiquinones dolichol and heme. Plays a major role in the cell
CC       antiviral state induced by type I and type II interferon. Displays
CC       antiviral effect against HIV-1 virus, hepatitis C virus, human
CC       cytomegalovirus, and aphaviruses, but not vesiculovirus.
CC   -!- COFACTOR: Binds 1 4Fe-4S cluster. The cluster is coordinated with
CC       3 cysteines and an exchangeable S-adenosyl-L-methionine (By
CC       similarity).
CC   -!- SUBUNIT: Interacts with FPPS.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC       membrane protein; Cytoplasmic side. Golgi apparatus. Note=Probably
CC       associates with the cytosolic side of the endoplasmic reticulum.
CC       Infection with human cytomegalovirus (HCMV) causes relocation to
CC       the Golgi apparatus and to cytoplasmic vacuoles which also contain
CC       HCMV proteins glycoprotein B and pp28.
CC   -!- INDUCTION: By interferon type I, type II and LPS. Little or no
CC       induction by interferon gamma is observed in monocytic cell lines.
CC       Induced by infection with human cytomegalovirus (HMCV), hepatitis
CC       C virus, yellow fever virus and Sendai virus, presumably through
CC       type I interferon pathway.
CC   -!- MISCELLANEOUS: Up-regulated in atherosclerosis. Latent viruses
CC       like HCMV may be involved in atherogenesis by initiating local
CC       inflammation. This may induce up-regulation of antiviral gene
CC       RSAD2, which modulates lipids synthesis, and thus could play a
CC       role in abnormal lipid accumulation leading to atherosclerosis.
CC   -!- SIMILARITY: Belongs to the RSAD2 family.
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DR   EMBL; AF026941; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AF442151; AAL50053.1; -; mRNA.
DR   EMBL; AC017076; AAY14802.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAX01034.1; -; Genomic_DNA.
DR   EMBL; BC017969; AAH17969.1; -; mRNA.
DR   IPI; IPI00291463; -.
DR   RefSeq; NP_542388.2; -.
DR   UniGene; Hs.17518; -.
DR   STRING; Q8WXG1; -.
DR   PRIDE; Q8WXG1; -.
DR   Ensembl; ENST00000382040; ENSP00000371471; ENSG00000134321; Homo sapiens.
DR   Ensembl; ENST00000442639; ENSP00000406427; ENSG00000134321; Homo sapiens.
DR   GeneID; 91543; -.
DR   KEGG; hsa:91543; -.
DR   NMPDR; fig|9606.3.peg.17475; -.
DR   UCSC; uc002qyp.1; human.
DR   CTD; 91543; -.
DR   GeneCards; GC02P006969; -.
DR   HGNC; HGNC:30908; RSAD2.
DR   MIM; 607810; gene.
DR   PharmGKB; PA134937442; -.
DR   HOVERGEN; Q8WXG1; -.
DR   OMA; LQKLRTW; -.
DR   NextBio; 77284; -.
DR   ArrayExpress; Q8WXG1; -.
DR   Bgee; Q8WXG1; -.
DR   CleanEx; HS_RSAD2; -.
DR   Genevestigator; Q8WXG1; -.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0009898; C:internal side of plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0003824; F:catalytic activity; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0051536; F:iron-sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR   InterPro; IPR006638; Elp3/MiaB/NifB.
DR   InterPro; IPR007197; Radical_SAM.
DR   Pfam; PF04055; Radical_SAM; 1.
DR   SMART; SM00729; Elp3; 1.
PE   1: Evidence at protein level;
KW   Antiviral defense; Atherosclerosis; Complete proteome;
KW   Endoplasmic reticulum; Golgi apparatus; Iron; Iron-sulfur; Membrane;
KW   Metal-binding; Polymorphism; S-adenosyl-L-methionine.
FT   CHAIN         1    361       Radical S-adenosyl methionine domain-
FT                                containing protein 2.
FT                                /FTId=PRO_0000309583.
FT   METAL        83     83       Iron-sulfur (4Fe-4S-S-AdoMet)
FT                                (Potential).
FT   METAL        87     87       Iron-sulfur (4Fe-4S-S-AdoMet)
FT                                (Potential).
FT   METAL        90     90       Iron-sulfur (4Fe-4S-S-AdoMet)
FT                                (Potential).
FT   VARIANT      42     42       L -> R (in dbSNP:rs17851586).
FT                                /FTId=VAR_036980.
FT   VARIANT      52     52       V -> I (in dbSNP:rs2305257).
FT                                /FTId=VAR_053974.
FT   CONFLICT     13     13       L -> F (in Ref. 1; AF026941).
FT   CONFLICT    216    217       VA -> IP (in Ref. 1; AF026941).
SQ   SEQUENCE   361 AA;  42170 MW;  ED014743CE1568DF CRC64;
     MWVLTPAAFA GKLLSVFRQP LSSLWRSLVP LFCWLRATFW LLATKRRKQQ LVLRGPDETK
     EEEEDPPLPT TPTSVNYHFT RQCNYKCGFC FHTAKTSFVL PLEEAKRGLL LLKEAGMEKI
     NFSGGEPFLQ DRGEYLGKLV RFCKVELRLP SVSIVSNGSL IRERWFQNYG EYLDILAISC
     DSFDEEVNVL IGRGQGKKNH VENLQKLRRW CRDYRVAFKI NSVINRFNVE EDMTEQIKAL
     NPVRWKVFQC LLIEGENCGE DALREAERFV IGDEEFERFL ERHKEVSCLV PESNQKMKDS
     YLILDEYMRF LNCRKGRKDP SKSILDVGVE EAIKFSGFDE KMFLKRGGKY IWSKADLKLD
     W
//