Reviewed, UniProtKB/Swiss-Prot Q8WXG1 (RSAD2_HUMAN)

Names and origin

Protein names

Recommended name:
    Radical S-adenosyl methionine domain-containing protein 2
Alternative name(s):
    Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible
      Short name=Viperin
    Cytomegalovirus-induced gene 5 protein

Gene names

Name:	RSAD2
Synonyms:	CIG5

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	361 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (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. Ref.2 Ref.7 Ref.10 Ref.11 Ref.13
Cofactor	Binds 1 4Fe-4S cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine By similarity.
Subunit structure	Interacts with FPPS. Ref.12
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. Ref.2 Ref.10
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. Ref.2 Ref.7 Ref.1 Ref.8 Ref.9
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.
Sequence similarities	Belongs to the RSAD2 family.

Ontologies

Keywords
Biological process	Antiviral defense
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Disease	Atherosclerosis
Ligand	Iron Iron-sulfur Metal-binding S-adenosyl-L-methionine
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	defense response to virus Ref.1 Ref.7 Ref.10 Inferred from direct assay. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from direct assay. Source: UniProtKB internal side of plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	catalytic activity Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW iron-sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 361	361	Radical S-adenosyl methionine domain-containing protein 2		PRO_0000309583
Sites
	Metal binding	83	1	Iron-sulfur (4Fe-4S-S-AdoMet) Potential
	Metal binding	87	1	Iron-sulfur (4Fe-4S-S-AdoMet) Potential
	Metal binding	90	1	Iron-sulfur (4Fe-4S-S-AdoMet) Potential
Natural variations
	Natural variant	42	1	L → R: dbSNP rs17851586. Ref.5		VAR_036980
	Natural variant	52	1	V → I: dbSNP rs2305257.		VAR_053974
Experimental info
	Sequence conflict	13	1	L → F in AF026941. Ref.1
	Sequence conflict	216 – 217	2	VA → IP in AF026941. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8WXG1-1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: ED014743CE1568DF	FASTA	361	42,170
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Use of differential display analysis to assess the effect of human cytomegalovirus infection on the accumulation of cellular RNAs: induction of interferon-responsive RNAs." Zhu H., Cong J.-P., Shenk T. Proc. Natl. Acad. Sci. U.S.A. 94:13985-13990(1997) [PubMed: 9391139] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION. Tissue: Foreskin fibroblast.
[2]	"Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus." Chin K.-C., Cresswell P. Proc. Natl. Acad. Sci. U.S.A. 98:15125-15130(2001) [PubMed: 11752458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INDUCTION. Tissue: Macrophage.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." 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. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-42. Tissue: Prostate.
[6]	"The antiviral cytomegalovirus inducible gene 5/viperin is expressed in atherosclerosis and regulated by proinflammatory agents." Olofsson P.S., Jatta K., Waagsaeter D., Gredmark S., Hedin U., Paulsson-Berne G., Soederberg-Naucler C., Hansson G.K., Sirsjoe A. Arterioscler. Thromb. Vasc. Biol. 25:E113-E116(2005) [PubMed: 15890971] [Abstract] Cited for: UP-REGULATION IN ATHEROSCLEROSIS.
[7]	"Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector." Helbig K.J., Lau D.T.-Y., Semendric L., Harley H.A.J., Beard M.R. Hepatology 42:702-710(2005) [PubMed: 16108059] [Abstract] Cited for: FUNCTION, INDUCTION.
[8]	"Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord endothelial cells and induce novel changes in gene expression." Khaiboullina S.F., Rizvanov A.A., Holbrook M.R., St Jeor S. Virology 342:167-176(2005) [PubMed: 16150475] [Abstract] Cited for: INDUCTION.
[9]	"Toll-like receptor-dependent and -independent viperin gene expression and counter-regulation by PRDI-binding factor-1/BLIMP1." Severa M., Coccia E.M., Fitzgerald K.A. J. Biol. Chem. 281:26188-26195(2006) [PubMed: 16849320] [Abstract] Cited for: INDUCTION.
[10]	"TLR3 ligation activates an antiviral response in human fetal astrocytes: a role for viperin/cig5." Rivieccio M.A., Suh H.-S., Zhao Y., Zhao M.-L., Chin K.-C., Lee S.C., Brosnan C.F. J. Immunol. 177:4735-4741(2006) [PubMed: 16982913] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"Identification and characterization of interferon-induced proteins that inhibit alphavirus replication." Zhang Y., Burke C.W., Ryman K.D., Klimstra W.B. J. Virol. 81:11246-11255(2007) [PubMed: 17686841] [Abstract] Cited for: FUNCTION.
[12]	"The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts." Wang X., Hinson E.R., Cresswell P. Cell Host Microbe 2:96-105(2007) [PubMed: 18005724] [Abstract] Cited for: INTERACTION WITH FPPS.
[13]	"Influenza virus not cRAFTy enough to dodge viperin." Waheed A.A., Freed E.O. Cell Host Microbe 2:71-72(2007) [PubMed: 18005719] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF026941 mRNA. No translation available. AF442151 mRNA. Translation: AAL50053.1. AC017076 Genomic DNA. Translation: AAY14802.1. CH471053 Genomic DNA. Translation: EAX01034.1. BC017969 mRNA. Translation: AAH17969.1.
IPI	IPI00291463.
RefSeq	NP_542388.2.
UniGene	Hs.17518
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q8WXG1.
Proteomic databases
PRIDE	Q8WXG1.
Genome annotation databases
Ensembl	ENST00000382040; ENSP00000371471; ENSG00000134321; Homo sapiens. [Genome view] ENST00000442639; ENSP00000406427; ENSG00000134321; Homo sapiens. [Genome view]
GeneID	91543.
KEGG	hsa:91543.
NMPDR	fig|9606.3.peg.17475.
UCSC	uc002qyp.1. human.
Organism-specific databases
CTD	91543.
GeneCards	GC02P006969.
HGNC	HGNC:30908. RSAD2.
MIM	607810. gene.
PharmGKB	PA134937442.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q8WXG1.
OMA	LQKLRTW.
Gene expression databases
ArrayExpress	Q8WXG1.
Bgee	Q8WXG1.
CleanEx	HS_RSAD2.
Genevestigator	Q8WXG1.
Family and domain databases
InterPro	IPR006638. Elp3/MiaB/NifB. IPR007197. Radical_SAM. [Graphical view]
Pfam	PF04055. Radical_SAM. 1 hit. [Graphical view]
SMART	SM00729. Elp3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	77284.
SOURCE	Search...

Entry information

Entry name

RSAD2_HUMAN

Accession

Primary (citable) accession number: Q8WXG1
Secondary accession number(s): Q8WVI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 13, 2007
Last sequence update:	March 1, 2002
Last modified:	November 3, 2009
This is version 54 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.