RSAD2_PIG
ID RSAD2_PIG Reviewed; 362 AA.
AC Q9MZU4;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Radical S-adenosyl methionine domain-containing protein 2;
DE EC=4.2.-.- {ECO:0000250|UniProtKB:Q8WXG1};
DE AltName: Full=Inflammatory response gene 6 protein;
DE AltName: Full=Viperin;
DE AltName: Full=Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible;
GN Name=RSAD2 {ECO:0000250|UniProtKB:Q8WXG1};
GN Synonyms=CIG6 {ECO:0000303|Ref.1}, IRG6 {ECO:0000303|Ref.1};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1] {ECO:0000312|EMBL:AAF74525.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Dorfleutner A., Stehlik C., Koranda M., Kroismayr R., Binder B.R., Lipp J.;
RT "Inflammatory response gene 6 (IRG6/CIG6) is regulated by NF-kB in
RT endothelial cells.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, INTERACTION WITH PORCINE EPIDEMIC DIARRHEA VIRUS PROTEIN N
RP (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=32719955; DOI=10.1007/s00705-020-04747-8;
RA Wu J., Chi H., Fu Y., Cao A., Shi J., Zhu M., Zhang L., Hua D., Huang J.;
RT "The antiviral protein viperin interacts with the viral N protein to
RT inhibit proliferation of porcine epidemic diarrhea virus.";
RL Arch. Virol. 165:2279-2289(2020).
RN [3]
RP FUNCTION, AND INTERACTION WITH CLASSICAL SWINE FEVER VIRUS PROTEIN NS5A
RP (MICROBIAL INFECTION).
RX PubMed=31517388; DOI=10.1002/jmv.25595;
RA Xu C., Feng L., Chen P., Li A., Guo S., Jiao X., Zhang C., Zhao Y., Jin X.,
RA Zhong K., Guo Y., Zhu H., Han L., Yang G., Li H., Wang Y.;
RT "Viperin inhibits classical swine fever virus replication by interacting
RT with viral nonstructural 5A protein.";
RL J. Med. Virol. 92:149-160(2020).
CC -!- FUNCTION: Interferon-inducible antiviral protein which plays a major
CC role in the cell antiviral state induced by type I and type II
CC interferon. Catalyzes the conversion of cytidine triphosphate (CTP) to
CC 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) via a SAM-dependent radical
CC mechanism. In turn, ddhCTP acts as a chain terminator for the RNA-
CC dependent RNA polymerases from multiple viruses and directly inhibits
CC viral replication. Therefore, inhibits a wide range of DNA and RNA
CC viruses (PubMed:32719955, PubMed:31517388). Promotes also TLR7 and
CC TLR9-dependent production of IFN-beta production in plasmacytoid
CC dendritic cells (pDCs) by facilitating 'Lys-63'-linked ubiquitination
CC of IRAK1 by TRAF6. Plays a role in CD4+ T-cells activation and
CC differentiation. Facilitates T-cell receptor (TCR)-mediated GATA3
CC activation and optimal T-helper 2 (Th2) cytokine production by
CC modulating NFKB1 and JUNB activities. Can inhibit secretion of soluble
CC proteins (By similarity). {ECO:0000250|UniProtKB:Q8WXG1,
CC ECO:0000269|PubMed:31517388, ECO:0000269|PubMed:32719955}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + CTP + S-adenosyl-L-methionine = 3'-deoxy-3',4'-
CC didehydro-CTP + 5'-deoxyadenosine + A + H(+) + H2O + L-methionine;
CC Xref=Rhea:RHEA:65944, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17319, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:37563, ChEBI:CHEBI:57844, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:166821; Evidence={ECO:0000250|UniProtKB:Q8WXG1};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:Q8WXG1};
CC Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000250|UniProtKB:Q8WXG1};
CC -!- ACTIVITY REGULATION: IRAK1 and TRAF6 synergistically activate RSAD2
CC increasing its activity with CTP as substrate about 10-fold.
CC {ECO:0000250|UniProtKB:Q8WXG1}.
CC -!- SUBUNIT: Homodimer. Interacts with IRAK1 and TRAF6. Interacts with
CC FPPS. Interacts with HADHB. Interacts (via C-terminus) with VAPA/VAP33
CC (via C-terminus). {ECO:0000250, ECO:0000250|UniProtKB:Q8WXG1}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8WXG1}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8WXG1}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q8WXG1}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q8WXG1}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q8WXG1}. Lipid droplet
CC {ECO:0000250|UniProtKB:Q8WXG1}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q8WXG1}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q8WXG1}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q8WXG1}.
CC -!- INDUCTION: By interferon type I, type II and LPS.
CC -!- DOMAIN: The N-terminal region (1-42) is necessary for its localization
CC to the endoplasmic reticulum membrane and lipid droplet. {ECO:0000250}.
CC -!- PTM: Acetylated by HAT1. HAT1-mediated acetylation of Lys-198 in turn
CC recruits UBE4A that stimulates RSAD2 polyubiquitination leading to
CC proteasomal degradation. {ECO:0000250|UniProtKB:Q8WXG1}.
CC -!- PTM: 'Lys-6'-linked polyubiquitination at Lys-207 leads to RSAD2
CC protein degradation. {ECO:0000250|UniProtKB:Q8WXG1}.
CC -!- SIMILARITY: Belongs to the radical SAM superfamily. RSAD2 family.
CC {ECO:0000305}.
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DR EMBL; AF156929; AAF74525.1; -; mRNA.
DR RefSeq; NP_998982.1; NM_213817.1.
DR AlphaFoldDB; Q9MZU4; -.
DR SMR; Q9MZU4; -.
DR STRING; 9823.ENSSSCP00000009218; -.
DR PaxDb; Q9MZU4; -.
DR PRIDE; Q9MZU4; -.
DR GeneID; 396752; -.
DR KEGG; ssc:396752; -.
DR CTD; 91543; -.
DR eggNOG; ENOG502QQMH; Eukaryota.
DR InParanoid; Q9MZU4; -.
DR OrthoDB; 1098093at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
DR GO; GO:0035710; P:CD4-positive, alpha-beta T cell activation; ISS:UniProtKB.
DR GO; GO:0043367; P:CD4-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0050709; P:negative regulation of protein secretion; ISS:UniProtKB.
DR GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; ISS:UniProtKB.
DR GO; GO:0034157; P:positive regulation of toll-like receptor 7 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; ISS:UniProtKB.
DR GO; GO:0009615; P:response to virus; ISS:UniProtKB.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR007197; rSAM.
DR Pfam; PF04055; Radical_SAM; 1.
DR SFLD; SFLDS00029; Radical_SAM; 1.
DR SMART; SM00729; Elp3; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Acetylation; Antiviral defense; Endoplasmic reticulum;
KW Golgi apparatus; Immunity; Innate immunity; Iron; Iron-sulfur;
KW Isopeptide bond; Lipid droplet; Lyase; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion inner membrane; Mitochondrion outer membrane;
KW Reference proteome; S-adenosyl-L-methionine; Ubl conjugation.
FT CHAIN 1..362
FT /note="Radical S-adenosyl methionine domain-containing
FT protein 2"
FT /id="PRO_0000309587"
FT DOMAIN 70..290
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT REGION 49..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 84
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250|UniProtKB:Q8CBB9"
FT BINDING 88
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250|UniProtKB:Q8CBB9"
FT BINDING 91
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250|UniProtKB:Q8CBB9"
FT MOD_RES 198
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG1"
FT CROSSLNK 207
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG1"
SQ SEQUENCE 362 AA; 41864 MW; 01EF0CDAF4282FC5 CRC64;
MWTLVPVTFA LRLLSTFVQP LGSLGSSLGP LFLWLWAAFW RAGGDRSRQQ LQGKTEAGEP
PRAQEDSHLP TTPTSVNYHF TRQCNYKCGF CFHTAKTSFV LPLEEAKRGL WLLKEAGMEK
INFSGGEPFI HDRGEYLGKL VRFCKEELQL PSVSIVSNGS LIWERWFKSY GEYLDILAIS
CDSFDEQVNV LIGRGQGKKN HVENLQKLRT WCRDYKVAFK INSVINRFNV EEDMTEHIKA
LNPVRWKVFQ CLLIEGENVG EDALREAEQF VISDEEFEEF LDRHKDVSCL VPESNRQMRD
SYLILDEYMR FLNCRNGRKD PSKSILDVGV EKAIKFSGFD EKMFLKRGGK YVWSKADLKL
DW
