RSAD2_RAT
ID RSAD2_RAT Reviewed; 360 AA.
AC O70600;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Radical S-adenosyl methionine domain-containing protein 2;
DE EC=4.2.-.- {ECO:0000250|UniProtKB:Q8WXG1};
DE AltName: Full=Bone-expressed sequence tag 5 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=Best5 {ECO:0000312|RGD:620495};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAA68971.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP INDUCTION.
RC STRAIN=Wistar {ECO:0000312|EMBL:CAA68971.1};
RC TISSUE=Bone {ECO:0000312|EMBL:CAA68971.1};
RX PubMed=10698968; DOI=10.1096/fasebj.14.3.523;
RA Grewal T.S., Genever P.G., Brabbs A.C., Birch M., Skerry T.M.;
RT "Best5: a novel interferon-inducible gene expressed during bone
RT formation.";
RL FASEB J. 14:523-531(2000).
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. 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 -!- TISSUE SPECIFICITY: In neonatal rat tibia, specifically localized in
CC cells of the periosteum, in osteoblasts lining endosteal and peristeal
CC bone surfaces, to articular surfaces of cartilage and in perichondral
CC cells but not in chondrocytes (at protein level). Expressed
CC predominantly in bone marrow and spleen. {ECO:0000269|PubMed:10698968}.
CC -!- DEVELOPMENTAL STAGE: Not detected in undifferentiated primary
CC osteoblasts. Expression increases during differentiation and declines
CC to much reduced levels in mature osteoblasts.
CC {ECO:0000269|PubMed:10698968}.
CC -!- INDUCTION: By interferon type I, type II and LPS. Interferon alpha
CC induction is rapid and transient, peaks 4-6 hours after stimulation and
CC returns to basal levels 24 hours after stimulation. Interferon gamma
CC elicits a more prolonged response where expression remains elevated 48
CC hours after stimulation. Induced by infection with Vesicular stomatitis
CC virus and pseudorabies virus, presumably through type I interferon
CC pathway. {ECO:0000269|PubMed:10698968}.
CC -!- DOMAIN: The N-terminal region (1-41) 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-196 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-205 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; Y07704; CAA68971.1; -; mRNA.
DR RefSeq; NP_620236.1; NM_138881.1.
DR AlphaFoldDB; O70600; -.
DR SMR; O70600; -.
DR STRING; 10116.ENSRNOP00000010092; -.
DR PaxDb; O70600; -.
DR PRIDE; O70600; -.
DR GeneID; 65190; -.
DR KEGG; rno:65190; -.
DR CTD; 91543; -.
DR RGD; 620495; Rsad2.
DR eggNOG; ENOG502QQMH; Eukaryota.
DR HOGENOM; CLU_049058_2_1_1; -.
DR InParanoid; O70600; -.
DR OrthoDB; 1098093at2759; -.
DR PhylomeDB; O70600; -.
DR PRO; PR:O70600; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; O70600; RN.
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; ISO:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0001503; P:ossification; IDA:RGD.
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:0030278; P:regulation of ossification; IDA:RGD.
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 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..360
FT /note="Radical S-adenosyl methionine domain-containing
FT protein 2"
FT /id="PRO_0000309586"
FT DOMAIN 68..288
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT REGION 44..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 47..61
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 82
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 86
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 MOD_RES 196
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG1"
FT CROSSLNK 205
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8WXG1"
SQ SEQUENCE 360 AA; 41255 MW; 4947AF2A286CB500 CRC64;
MLVPTALAAR LLSLFQQQLG SLWSGLAMLF CWLRIALGWP DPGKGQPRVR GEPKETQETH
EDPGSAQPTT PVSVNYHFTR QCNYKCGFCF HTAKTSFVLP LEEAKRGLLL LKQAGMEKIN
FSGGEPFLQD RGEYLGKLVR FCKEELALPS VSIVSNGSLI RERWFKDYGD YLDILAISCD
SFDEQVNVLI GRGQGKKNHV ENLQKLRKWC RDYKVAFKIN SVINRFNVDE DMNEHIKALS
PVRWKVFQCL LIEGENSGED ALREAERFLI SNEEFEAFLQ RHKDVSCLVP ESNQKMKDSY
LILDEYMRFL NCTGGRKDPS RSILDVGVEE AIKFSGFDEK MFLKRGGKYV WSKADLKLDW
