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Protein

Radical S-adenosyl methionine domain-containing protein 2

Gene

Rsad2

Organism
Rattus norvegicus (Rat)
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 viruses, including west Nile virus (WNV), dengue virus, sindbis virus, influenza A virus, sendai virus and vesicular stomatitis virus (VSV). 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 diphospate 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 (By similarity).By similarity

Cofactori

[4Fe-4S] clusterBy similarityNote: Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi82 – 821Iron-sulfur (4Fe-4S-S-AdoMet)By similarity
Metal bindingi86 – 861Iron-sulfur (4Fe-4S-S-AdoMet)By similarity
Metal bindingi89 – 891Iron-sulfur (4Fe-4S-S-AdoMet)By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity

Keywords - Ligandi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Radical S-adenosyl methionine domain-containing protein 2
Alternative name(s):
Bone-expressed sequence tag 5 protein
Viperin
Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible
Gene namesi
Name:Rsad2By similarity
Synonyms:Best5Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620495. Rsad2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Lipid droplet, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 360360Radical S-adenosyl methionine domain-containing protein 2PRO_0000309586Add
BLAST

Proteomic databases

PaxDbiO70600.
PRIDEiO70600.

Expressioni

Tissue specificityi

In neonatal rat tibia, specifically localized in cells of the periosteum, in osteoblasts lining endosteal and peristeal bone surfaces, to articular surfaces of cartilage and in perichondral cells but not in chondrocytes (at protein level). Expressed predominantly in bone marrow and spleen.1 Publication

Developmental stagei

Not detected in undifferentiated primary osteoblasts. Expression increases during differentiation and declines to much reduced levels in mature osteoblasts.1 Publication

Inductioni

By interferon type I, type II and LPS. Interferon alpha induction is rapid and transient, peaks 4-6 hours after stimulation and returns to basal levels 24 hours after stimulation. Interferon gamma elicits a more prolonged response where expression remains elevated 48 hours after stimulation. Induced by infection with Vesicular stomatitis virus and pseudorabies virus, presumably through type I interferon pathway.1 Publication

Gene expression databases

GenevisibleiO70600. RN.

Interactioni

Subunit structurei

Homodimer. Interacts (via C-terminus) with VAPA/VAP33 (via C-terminus) and inhibits its interaction with hepatitis virus C (HCV) protein NS5A. Interacts with HADHB, IRAK1 and TRAF6 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000010092.

Structurei

3D structure databases

ProteinModelPortaliO70600.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The N-terminal region (1-41) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet.By similarity

Sequence similaritiesi

Belongs to the radical SAM superfamily. RSAD2 family.Curated

Phylogenomic databases

eggNOGiENOG410IGZE. Eukaryota.
ENOG410XQM5. LUCA.
HOGENOMiHOG000194793.
HOVERGENiHBG053099.
InParanoidiO70600.
KOiK15045.
OMAiINRFNVE.
OrthoDBiEOG7FFMRW.
PhylomeDBiO70600.

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.

O70600-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLVPTALAAR LLSLFQQQLG SLWSGLAMLF CWLRIALGWP DPGKGQPRVR
60 70 80 90 100
GEPKETQETH EDPGSAQPTT PVSVNYHFTR QCNYKCGFCF HTAKTSFVLP
110 120 130 140 150
LEEAKRGLLL LKQAGMEKIN FSGGEPFLQD RGEYLGKLVR FCKEELALPS
160 170 180 190 200
VSIVSNGSLI RERWFKDYGD YLDILAISCD SFDEQVNVLI GRGQGKKNHV
210 220 230 240 250
ENLQKLRKWC RDYKVAFKIN SVINRFNVDE DMNEHIKALS PVRWKVFQCL
260 270 280 290 300
LIEGENSGED ALREAERFLI SNEEFEAFLQ RHKDVSCLVP ESNQKMKDSY
310 320 330 340 350
LILDEYMRFL NCTGGRKDPS RSILDVGVEE AIKFSGFDEK MFLKRGGKYV
360
WSKADLKLDW
Length:360
Mass (Da):41,255
Last modified:August 1, 1998 - v1
Checksum:i4947AF2A286CB500
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y07704 mRNA. Translation: CAA68971.1.
RefSeqiNP_620236.1. NM_138881.1.
UniGeneiRn.14882.

Genome annotation databases

GeneIDi65190.
KEGGirno:65190.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y07704 mRNA. Translation: CAA68971.1.
RefSeqiNP_620236.1. NM_138881.1.
UniGeneiRn.14882.

3D structure databases

ProteinModelPortaliO70600.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000010092.

Proteomic databases

PaxDbiO70600.
PRIDEiO70600.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi65190.
KEGGirno:65190.

Organism-specific databases

CTDi91543.
RGDi620495. Rsad2.

Phylogenomic databases

eggNOGiENOG410IGZE. Eukaryota.
ENOG410XQM5. LUCA.
HOGENOMiHOG000194793.
HOVERGENiHBG053099.
InParanoidiO70600.
KOiK15045.
OMAiINRFNVE.
OrthoDBiEOG7FFMRW.
PhylomeDBiO70600.

Miscellaneous databases

PROiO70600.

Gene expression databases

GenevisibleiO70600. RN.

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...

Publicationsi

  1. "Best5: a novel interferon-inducible gene expressed during bone formation."
    Grewal T.S., Genever P.G., Brabbs A.C., Birch M., Skerry T.M.
    FASEB J. 14:523-531(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
    Strain: WistarImported.
    Tissue: BoneImported.

Entry informationi

Entry nameiRSAD2_RAT
AccessioniPrimary (citable) accession number: O70600
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: August 1, 1998
Last modified: June 8, 2016
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.