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Protein

Radical S-adenosyl methionine domain-containing protein 2

Gene

RSAD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

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 Publication1
Metal bindingi87Iron-sulfur (4Fe-4S-S-AdoMet)1 Publication1
Metal bindingi90Iron-sulfur (4Fe-4S-S-AdoMet)1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processAntiviral defense, Host-virus interaction, Immunity, Innate immunity
Ligand4Fe-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

EuPathDBiHostDB:ENSG00000134321.11
HGNCiHGNC:30908 RSAD2
MIMi607810 gene
neXtProtiNX_Q8WXG1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi75031

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 Expressed in 199 organ(s), highest expression level in ectocervix
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 HADHB. Interacts (via C-terminus) with VAPA/VAP33 (via C-terminus).By similarity3 Publications
(Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein vMIA/UL37; this interaction results in RSAD2/viperin relocalization from the endoplasmic reticulum to the mitochondria.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi124843, 3 interactors
IntActiQ8WXG1, 8 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
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR006638 Elp3/MiaB/NifB
IPR007197 rSAM
IPR034395 SPASM/twitch_domain-containing
PfamiView protein in Pfam
PF04055 Radical_SAM, 1 hit
SFLDiSFLDG01067 SPASM/twitch_domain_containing, 1 hit
SFLDS00029 Radical_SAM, 2 hits
SMARTiView protein in SMART
SM00729 Elp3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J674C9J674_HUMAN
Radical S-adenosyl methionine domai...
RSAD2
141Annotation score:

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 → R1 PublicationCorresponds to variant dbSNP:rs17851586Ensembl.1
Natural variantiVAR_05397452V → I. Corresponds to variant dbSNP:rs2305257Ensembl.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

Similar proteinsi

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
IntActiQ8WXG1, 8 interactors
STRINGi9606.ENSP00000371471

PTM databases

iPTMnetiQ8WXG1
PhosphoSitePlusiQ8WXG1

Polymorphism and mutation databases

BioMutaiRSAD2
DMDMi74724033

Proteomic databases

PaxDbiQ8WXG1
PeptideAtlasiQ8WXG1
PRIDEiQ8WXG1
ProteomicsDBi75031

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
EuPathDBiHostDB:ENSG00000134321.11
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
PROiPR:Q8WXG1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134321 Expressed in 199 organ(s), highest expression level in ectocervix
CleanExiHS_RSAD2
ExpressionAtlasiQ8WXG1 baseline and differential
GenevisibleiQ8WXG1 HS

Family and domain databases

Gene3Di3.20.20.70, 1 hit
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR006638 Elp3/MiaB/NifB
IPR007197 rSAM
IPR034395 SPASM/twitch_domain-containing
PfamiView protein in Pfam
PF04055 Radical_SAM, 1 hit
SFLDiSFLDG01067 SPASM/twitch_domain_containing, 1 hit
SFLDS00029 Radical_SAM, 2 hits
SMARTiView protein in SMART
SM00729 Elp3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRSAD2_HUMAN
AccessioniPrimary (citable) accession number: Q8WXG1
Secondary accession number(s): Q8WVI4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: March 1, 2002
Last modified: November 7, 2018
This is version 123 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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