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Protein

Radical S-adenosyl methionine domain-containing protein 2

Gene

RSAD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Interferon-inducible iron-sulfur (4FE-4S) cluster-binding antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon. Can inhibit a wide range of DNA and RNA viruses, including human cytomegalovirus (HCMV), hepatitis C virus (HCV), west Nile virus (WNV), dengue virus, sindbis virus, influenza A virus, sendai virus, vesicular stomatitis virus (VSV), and human immunodeficiency virus (HIV-1). Displays antiviral activity against influenza A virus by inhibiting the budding of the virus from the plasma membrane by disturbing the lipid rafts. This is accomplished, at least in part, through binding and inhibition of the enzyme farnesyl diphosphate synthase (FPPS), which is essential for the biosynthesis of isoprenoid-derived lipids. Promotes TLR7 and TLR9-dependent production of IFN-beta production in plasmacytoid dendritic cells (pDCs) by facilitating Lys-63'-linked ubiquitination of IRAK1. Plays a role in CD4+ T-cells activation and differentiation. Facilitates T-cell receptor (TCR)-mediated GATA3 activation and optimal T-helper 2 (Th2) cytokine production by modulating NFKB1 and JUNB activities. Can inhibit secretion of soluble proteins.6 Publications

Cofactori

[4Fe-4S] cluster3 PublicationsNote: Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi83Iron-sulfur (4Fe-4S-S-AdoMet)1
Metal bindingi87Iron-sulfur (4Fe-4S-S-AdoMet)1
Metal bindingi90Iron-sulfur (4Fe-4S-S-AdoMet)1

GO - Molecular functioni

  • 4 iron, 4 sulfur cluster binding Source: UniProtKB
  • catalytic activity Source: InterPro
  • metal ion binding Source: UniProtKB-KW
  • protein self-association Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Antiviral defense, Host-virus interaction, Immunity, Innate immunity

Keywords - Ligandi

4Fe-4S, Iron, Iron-sulfur, Metal-binding, S-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiR-HSA-909733. Interferon alpha/beta signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Radical S-adenosyl methionine domain-containing protein 2
Alternative name(s):
Cytomegalovirus-induced gene 5 protein
Viperin
Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible
Gene namesi
Name:RSAD2Imported
Synonyms:CIG5Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:30908. RSAD2.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB
  • Golgi apparatus Source: UniProtKB-SubCell
  • lipid particle Source: UniProtKB
  • mitochondrial inner membrane Source: UniProtKB
  • mitochondrial outer membrane Source: UniProtKB
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Lipid droplet, Membrane, Mitochondrion, Mitochondrion inner membrane, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi83C → A: Loss of ability to assemble an Fe-S cluster and significant decrease in protein stability. 1 Publication1
Mutagenesisi87C → A: Loss of ability to assemble an Fe-S cluster and significant decrease in protein stability. 1 Publication1
Mutagenesisi90C → A: Loss of ability to assemble an Fe-S cluster and significant decrease in protein stability. 1 Publication1

Keywords - Diseasei

Atherosclerosis

Organism-specific databases

DisGeNETi91543.
OpenTargetsiENSG00000134321.
PharmGKBiPA134937442.

Polymorphism and mutation databases

BioMutaiRSAD2.
DMDMi74724033.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003095831 – 361Radical S-adenosyl methionine domain-containing protein 2Add BLAST361

Proteomic databases

PaxDbiQ8WXG1.
PeptideAtlasiQ8WXG1.
PRIDEiQ8WXG1.

PTM databases

iPTMnetiQ8WXG1.
PhosphoSitePlusiQ8WXG1.

Expressioni

Inductioni

By interferon type I, type II and bacterial lipopolysaccharides (LPS). Little or no induction by IFNG/IFN-gamma is observed in monocytic cell lines. Induced by infection with hepatitis C virus, yellow fever virus and Sendai virus, presumably through type I interferon pathway. Induction by infection with human cytomegalovirus (HCMV), stomatitis virus (VSV), chikungunya virus (CHIKV), Japanese encephalitis virus (JEV) occurs independent of the IFN pathway.5 Publications

Gene expression databases

BgeeiENSG00000134321.
CleanExiHS_RSAD2.
ExpressionAtlasiQ8WXG1. baseline and differential.
GenevisibleiQ8WXG1. HS.

Organism-specific databases

HPAiHPA041160.
HPA049409.

Interactioni

Subunit structurei

Homodimer. Interacts with IRAK1 and TRAF6 (By similarity). Interacts with FPPS. Interacts with human cytomegalovirus/HHV-5 protein vMIA/UL37; this interaction results in RSAD2/viperin relocalization from the endoplasmic reticulum to the mitochondria. Interacts with HADHB. Interacts (via C-terminus) with VAPA/VAP33 (via C-terminus) and inhibits its interaction with hepatitis virus C (HCV) protein NS5A.By similarity4 Publications

GO - Molecular functioni

  • protein self-association Source: UniProtKB

Protein-protein interaction databases

BioGridi124843. 3 interactors.
STRINGi9606.ENSP00000371471.

Structurei

3D structure databases

ProteinModelPortaliQ8WXG1.
SMRiQ8WXG1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The N-terminal region (1-42) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet.

Sequence similaritiesi

Belongs to the radical SAM superfamily. RSAD2 family.Curated

Phylogenomic databases

eggNOGiENOG410IGZE. Eukaryota.
ENOG410XQM5. LUCA.
GeneTreeiENSGT00390000013670.
HOGENOMiHOG000194793.
HOVERGENiHBG053099.
InParanoidiQ8WXG1.
KOiK15045.
OMAiINRFNVE.
OrthoDBiEOG091G0GXY.
PhylomeDBiQ8WXG1.
TreeFamiTF300085.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR006638. Elp3/MiaB/NifB.
IPR007197. rSAM.
IPR026372. Viperin.
[Graphical view]
PfamiPF04055. Radical_SAM. 1 hit.
[Graphical view]
SMARTiSM00729. Elp3. 1 hit.
[Graphical view]
TIGRFAMsiTIGR04278. viperin. 1 hit.

Sequencei

Sequence statusi: Complete.

Q8WXG1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWVLTPAAFA GKLLSVFRQP LSSLWRSLVP LFCWLRATFW LLATKRRKQQ
60 70 80 90 100
LVLRGPDETK EEEEDPPLPT TPTSVNYHFT RQCNYKCGFC FHTAKTSFVL
110 120 130 140 150
PLEEAKRGLL LLKEAGMEKI NFSGGEPFLQ DRGEYLGKLV RFCKVELRLP
160 170 180 190 200
SVSIVSNGSL IRERWFQNYG EYLDILAISC DSFDEEVNVL IGRGQGKKNH
210 220 230 240 250
VENLQKLRRW CRDYRVAFKI NSVINRFNVE EDMTEQIKAL NPVRWKVFQC
260 270 280 290 300
LLIEGENCGE DALREAERFV IGDEEFERFL ERHKEVSCLV PESNQKMKDS
310 320 330 340 350
YLILDEYMRF LNCRKGRKDP SKSILDVGVE EAIKFSGFDE KMFLKRGGKY
360
IWSKADLKLD W
Length:361
Mass (Da):42,170
Last modified:March 1, 2002 - v1
Checksum:iED014743CE1568DF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13L → F in AF026941 (PubMed:9391139).Curated1
Sequence conflicti216 – 217VA → IP in AF026941 (PubMed:9391139).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03698042L → R.1 PublicationCorresponds to variant rs17851586dbSNPEnsembl.1
Natural variantiVAR_05397452V → I.Corresponds to variant rs2305257dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1656.1.
RefSeqiNP_542388.2. NM_080657.4.
XP_011508716.1. XM_011510414.2.
UniGeneiHs.17518.

Genome annotation databases

EnsembliENST00000382040; ENSP00000371471; ENSG00000134321.
GeneIDi91543.
KEGGihsa:91543.
UCSCiuc002qyp.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1656.1.
RefSeqiNP_542388.2. NM_080657.4.
XP_011508716.1. XM_011510414.2.
UniGeneiHs.17518.

3D structure databases

ProteinModelPortaliQ8WXG1.
SMRiQ8WXG1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124843. 3 interactors.
STRINGi9606.ENSP00000371471.

PTM databases

iPTMnetiQ8WXG1.
PhosphoSitePlusiQ8WXG1.

Polymorphism and mutation databases

BioMutaiRSAD2.
DMDMi74724033.

Proteomic databases

PaxDbiQ8WXG1.
PeptideAtlasiQ8WXG1.
PRIDEiQ8WXG1.

Protocols and materials databases

DNASUi91543.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000382040; ENSP00000371471; ENSG00000134321.
GeneIDi91543.
KEGGihsa:91543.
UCSCiuc002qyp.2. human.

Organism-specific databases

CTDi91543.
DisGeNETi91543.
GeneCardsiRSAD2.
HGNCiHGNC:30908. RSAD2.
HPAiHPA041160.
HPA049409.
MIMi607810. gene.
neXtProtiNX_Q8WXG1.
OpenTargetsiENSG00000134321.
PharmGKBiPA134937442.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGZE. Eukaryota.
ENOG410XQM5. LUCA.
GeneTreeiENSGT00390000013670.
HOGENOMiHOG000194793.
HOVERGENiHBG053099.
InParanoidiQ8WXG1.
KOiK15045.
OMAiINRFNVE.
OrthoDBiEOG091G0GXY.
PhylomeDBiQ8WXG1.
TreeFamiTF300085.

Enzyme and pathway databases

ReactomeiR-HSA-909733. Interferon alpha/beta signaling.

Miscellaneous databases

ChiTaRSiRSAD2. human.
GenomeRNAii91543.
PROiQ8WXG1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134321.
CleanExiHS_RSAD2.
ExpressionAtlasiQ8WXG1. baseline and differential.
GenevisibleiQ8WXG1. HS.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR006638. Elp3/MiaB/NifB.
IPR007197. rSAM.
IPR026372. Viperin.
[Graphical view]
PfamiPF04055. Radical_SAM. 1 hit.
[Graphical view]
SMARTiSM00729. Elp3. 1 hit.
[Graphical view]
TIGRFAMsiTIGR04278. viperin. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRSAD2_HUMAN
AccessioniPrimary (citable) accession number: Q8WXG1
Secondary accession number(s): Q8WVI4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: March 1, 2002
Last modified: November 2, 2016
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.