RSAD2_BOVIN
ID RSAD2_BOVIN Reviewed; 363 AA.
AC Q2HJF9;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Radical S-adenosyl methionine domain-containing protein 2;
DE EC=4.2.-.- {ECO:0000250|UniProtKB:Q8WXG1};
DE AltName: Full=Viperin;
DE AltName: Full=Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible;
GN Name=RSAD2 {ECO:0000250|UniProtKB:Q8WXG1};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1] {ECO:0000312|EMBL:AAI05456.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford {ECO:0000312|EMBL:AAI05456.1};
RC TISSUE=Heart ventricle {ECO:0000312|EMBL:AAI05456.1};
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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. Catalyszes 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. Promotes also TLR7 and TLR9-dependent production of IFN-beta
CC production in plasmacytoid dendritic cells (pDCs) by facilitating 'Lys-
CC 63'-linked ubiquitination of IRAK1 by TRAF6. Plays a role in CD4+ T-
CC cells activation and differentiation. Facilitates T-cell receptor
CC (TCR)-mediated GATA3 activation and optimal T-helper 2 (Th2) cytokine
CC production by modulating NFKB1 and JUNB activities. Can inhibit
CC secretion of soluble proteins. {ECO:0000250|UniProtKB:Q8WXG1}.
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-199 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-208 leads to RSAD2
CC protein degradation. {ECO:0000250|UniProtKB:Q8WXG1}.
CC -!- SIMILARITY: Belongs to the radical SAM superfamily. RSAD2 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC105455; AAI05456.1; -; mRNA.
DR RefSeq; NP_001039406.1; NM_001045941.1.
DR AlphaFoldDB; Q2HJF9; -.
DR SMR; Q2HJF9; -.
DR STRING; 9913.ENSBTAP00000021373; -.
DR PaxDb; Q2HJF9; -.
DR PRIDE; Q2HJF9; -.
DR Ensembl; ENSBTAT00000021373; ENSBTAP00000021373; ENSBTAG00000016061.
DR GeneID; 506415; -.
DR KEGG; bta:506415; -.
DR CTD; 91543; -.
DR VEuPathDB; HostDB:ENSBTAG00000016061; -.
DR VGNC; VGNC:34176; RSAD2.
DR eggNOG; ENOG502QQMH; Eukaryota.
DR GeneTree; ENSGT00390000013670; -.
DR HOGENOM; CLU_049058_2_1_1; -.
DR InParanoid; Q2HJF9; -.
DR OMA; FRWKCFQ; -.
DR OrthoDB; 1098093at2759; -.
DR TreeFam; TF300085; -.
DR Proteomes; UP000009136; Chromosome 11.
DR Bgee; ENSBTAG00000016061; Expressed in milk and 103 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IEA:Ensembl.
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:0005739; C:mitochondrion; IBA:GO_Central.
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:0045071; P:negative regulation of viral genome replication; IEA:Ensembl.
DR GO; GO:0050778; P:positive regulation of immune response; IBA:GO_Central.
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 SMART; SM00729; Elp3; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 2: Evidence at transcript 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..363
FT /note="Radical S-adenosyl methionine domain-containing
FT protein 2"
FT /id="PRO_0000309582"
FT DOMAIN 71..291
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT REGION 46..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 47..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 85
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 89
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 92
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 199
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG1"
FT CROSSLNK 208
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG1"
SQ SEQUENCE 363 AA; 41672 MW; AE9EBC44C6DD96D6 CRC64;
MWMLVPIAFA LKLLNVFLQP LGSVWSSLGP LFLQLRAASW LAGGERSRPL QDRREAGEPG
RAEGEDGGDL PTTPTSVNYH FTRQCNYKCG FCFHTAKTSF VLPLEEAKKG LLMLKEAGME
KINFSGGEPF LQDRGEYLGR LVKFCKQELQ LPSVSIVSNG SLIRERWFQK YGEYLDILAI
SCDSFDEQVN VLIGRGQGKK NHVENLQKLR TWCKEYRVAF KINSVINRFN VDEDMKEQIT
ALNPVRWKVF QCLIIEGENS GEDALREAER FVISDEEFEA FLDRHKDVSC LVPESNQKMR
DSYLILDEYM RFLNCRNGRK DPSKSILDVG VEEAIKFSGF DEKMFLKRGG KYVWSKADLK
LDW
