RSAD2_HUMAN
ID RSAD2_HUMAN Reviewed; 361 AA.
AC Q8WXG1; Q8WVI4;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Radical S-adenosyl methionine domain-containing protein 2;
DE EC=4.2.-.- {ECO:0000269|PubMed:29925952, ECO:0000269|PubMed:30872404};
DE AltName: Full=Cytomegalovirus-induced gene 5 protein;
DE AltName: Full=Viperin {ECO:0000303|PubMed:30872404, ECO:0000303|PubMed:31812350};
DE AltName: Full=Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible;
GN Name=RSAD2 {ECO:0000312|EMBL:EAX01034.1};
GN Synonyms=CIG5 {ECO:0000312|EMBL:AAY14802.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC TISSUE=Foreskin fibroblast {ECO:0000269|PubMed:9391139};
RX PubMed=9391139; DOI=10.1073/pnas.94.25.13985;
RA Zhu H., Cong J.-P., Shenk T.;
RT "Use of differential display analysis to assess the effect of human
RT cytomegalovirus infection on the accumulation of cellular RNAs: induction
RT of interferon-responsive RNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:13985-13990(1997).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAL50053.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RC TISSUE=Macrophage {ECO:0000269|PubMed:11752458};
RX PubMed=11752458; DOI=10.1073/pnas.011593298;
RA Chin K.-C., Cresswell P.;
RT "Viperin (cig5), an IFN-inducible antiviral protein directly induced by
RT human cytomegalovirus.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:15125-15130(2001).
RN [3] {ECO:0000312|EMBL:AAY14802.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4] {ECO:0000312|EMBL:EAX01034.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAH17969.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-42.
RC TISSUE=Prostate {ECO:0000312|EMBL:AAH17969.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6] {ECO:0000305}
RP UP-REGULATION IN ATHEROSCLEROSIS.
RX PubMed=15890971; DOI=10.1161/01.atv.0000170130.85334.38;
RA Olofsson P.S., Jatta K., Waagsaeter D., Gredmark S., Hedin U.,
RA Paulsson-Berne G., Soederberg-Naucler C., Hansson G.K., Sirsjoe A.;
RT "The antiviral cytomegalovirus inducible gene 5/viperin is expressed in
RT atherosclerosis and regulated by proinflammatory agents.";
RL Arterioscler. Thromb. Vasc. Biol. 25:E113-E116(2005).
RN [7] {ECO:0000305}
RP FUNCTION, AND INDUCTION.
RX PubMed=16108059; DOI=10.1002/hep.20844;
RA Helbig K.J., Lau D.T.-Y., Semendric L., Harley H.A.J., Beard M.R.;
RT "Analysis of ISG expression in chronic hepatitis C identifies viperin as a
RT potential antiviral effector.";
RL Hepatology 42:702-710(2005).
RN [8] {ECO:0000305}
RP INDUCTION.
RX PubMed=16150475; DOI=10.1016/j.virol.2005.07.035;
RA Khaiboullina S.F., Rizvanov A.A., Holbrook M.R., St Jeor S.;
RT "Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord
RT endothelial cells and induce novel changes in gene expression.";
RL Virology 342:167-176(2005).
RN [9] {ECO:0000305}
RP INDUCTION.
RX PubMed=16849320; DOI=10.1074/jbc.m604516200;
RA Severa M., Coccia E.M., Fitzgerald K.A.;
RT "Toll-like receptor-dependent and -independent viperin gene expression and
RT counter-regulation by PRDI-binding factor-1/BLIMP1.";
RL J. Biol. Chem. 281:26188-26195(2006).
RN [10] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16982913; DOI=10.4049/jimmunol.177.7.4735;
RA Rivieccio M.A., Suh H.-S., Zhao Y., Zhao M.-L., Chin K.-C., Lee S.C.,
RA Brosnan C.F.;
RT "TLR3 ligation activates an antiviral response in human fetal astrocytes: a
RT role for viperin/cig5.";
RL J. Immunol. 177:4735-4741(2006).
RN [11]
RP FUNCTION.
RX PubMed=17686841; DOI=10.1128/jvi.01282-07;
RA Zhang Y., Burke C.W., Ryman K.D., Klimstra W.B.;
RT "Identification and characterization of interferon-induced proteins that
RT inhibit alphavirus replication.";
RL J. Virol. 81:11246-11255(2007).
RN [12]
RP INTERACTION WITH FPPS.
RX PubMed=18005724; DOI=10.1016/j.chom.2007.06.009;
RA Wang X., Hinson E.R., Cresswell P.;
RT "The interferon-inducible protein viperin inhibits influenza virus release
RT by perturbing lipid rafts.";
RL Cell Host Microbe 2:96-105(2007).
RN [13]
RP FUNCTION.
RX PubMed=18005719; DOI=10.1016/j.chom.2007.07.005;
RA Waheed A.A., Freed E.O.;
RT "Influenza virus not cRAFTy enough to dodge viperin.";
RL Cell Host Microbe 2:71-72(2007).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=19074433; DOI=10.1074/jbc.m807261200;
RA Hinson E.R., Cresswell P.;
RT "The N-terminal amphipathic alpha-helix of viperin mediates localization to
RT the cytosolic face of the endoplasmic reticulum and inhibits protein
RT secretion.";
RL J. Biol. Chem. 284:4705-4712(2009).
RN [15]
RP COFACTOR.
RX PubMed=20176015; DOI=10.1016/j.febslet.2010.02.041;
RA Duschene K.S., Broderick J.B.;
RT "The antiviral protein viperin is a radical SAM enzyme.";
RL FEBS Lett. 584:1263-1267(2010).
RN [16]
RP INTERACTION WITH HHV-5 PROTEIN UL37 (MICROBIAL INFECTION) AND HADHB, AND
RP SUBCELLULAR LOCATION.
RX PubMed=21527675; DOI=10.1126/science.1202007;
RA Seo J.Y., Yaneva R., Hinson E.R., Cresswell P.;
RT "Human cytomegalovirus directly induces the antiviral protein viperin to
RT enhance infectivity.";
RL Science 332:1093-1097(2011).
RN [17]
RP INTERACTION WITH VAPA.
RX PubMed=21957124; DOI=10.1099/vir.0.033860-0;
RA Wang S., Wu X., Pan T., Song W., Wang Y., Zhang F., Yuan Z.;
RT "Viperin inhibits hepatitis C virus replication by interfering with binding
RT of NS5A to host protein hVAP-33.";
RL J. Gen. Virol. 93:83-92(2012).
RN [18]
RP COFACTOR, AND MUTAGENESIS OF CYS-83; CYS-87 AND CYS-90.
RX PubMed=22363738; DOI=10.1371/journal.pone.0031797;
RA Haldar S., Paul S., Joshi N., Dasgupta A., Chattopadhyay K.;
RT "The presence of the iron-sulfur motif is important for the conformational
RT stability of the antiviral protein, Viperin.";
RL PLoS ONE 7:E31797-E31797(2012).
RN [19]
RP REVIEW.
RX PubMed=22177558; DOI=10.1016/j.chom.2011.11.004;
RA Seo J.Y., Yaneva R., Cresswell P.;
RT "Viperin: a multifunctional, interferon-inducible protein that regulates
RT virus replication.";
RL Cell Host Microbe 10:534-539(2011).
RN [20]
RP REVIEW.
RX PubMed=21142818; DOI=10.1089/jir.2010.0127;
RA Fitzgerald K.A.;
RT "The interferon inducible gene: Viperin.";
RL J. Interferon Cytokine Res. 31:131-135(2011).
RN [21]
RP REVIEW.
RX PubMed=22182524; DOI=10.1016/j.micinf.2011.11.015;
RA Mattijssen S., Pruijn G.J.;
RT "Viperin, a key player in the antiviral response.";
RL Microbes Infect. 14:419-426(2012).
RN [22]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29925952; DOI=10.1038/s41586-018-0238-4;
RA Gizzi A.S., Grove T.L., Arnold J.J., Jose J., Jangra R.K., Garforth S.J.,
RA Du Q., Cahill S.M., Dulyaninova N.G., Love J.D., Chandran K.,
RA Bresnick A.R., Cameron C.E., Almo S.C.;
RT "A naturally occurring antiviral ribonucleotide encoded by the human
RT genome.";
RL Nature 558:610-614(2018).
RN [23]
RP FUNCTION, INTERACTION WITH ENTEROVIRUS A71 PROTEIN 2C (MICROBIAL
RP INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=30587778; DOI=10.3390/v11010013;
RA Wei C., Zheng C., Sun J., Luo D., Tang Y., Zhang Y., Ke X., Liu Y.,
RA Zheng Z., Wang H.;
RT "Viperin Inhibits c Replication by Interacting with Viral 2C Protein.";
RL Viruses 11:0-0(2018).
RN [24]
RP FUNCTION, INTERACTION WITH HERPES SIMPLEX VIRUS 1/HHV-1 GLYCOPROTEIN D
RP (MICROBIAL INFECTION), SUBCELLULAR LOCATION, AND INTERACTION WITH TRAF6 AND
RP IRAK1.
RX PubMed=31921110; DOI=10.3389/fimmu.2019.02810;
RA Li M., Liao Z., Xu Z., Zou X., Wang Y., Peng H., Li Y., Ou X., Deng Y.,
RA Guo Y., Gan W., Peng T., Chen D., Cai M.;
RT "The Interaction Mechanism Between Herpes Simplex Virus 1 Glycoprotein D
RT and Host Antiviral Protein Viperin.";
RL Front. Immunol. 10:2810-2810(2019).
RN [25]
RP FUNCTION, INTERACTION WITH IRAK1 AND TRAF6, ACTIVITY REGULATION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=30872404; DOI=10.1074/jbc.ra119.007719;
RA Dumbrepatil A.B., Ghosh S., Zegalia K.A., Malec P.A., Hoff J.D.,
RA Kennedy R.T., Marsh E.N.G.;
RT "Viperin interacts with the kinase IRAK1 and the E3 ubiquitin ligase TRAF6,
RT coupling innate immune signaling to antiviral ribonucleotide synthesis.";
RL J. Biol. Chem. 294:6888-6898(2019).
RN [26]
RP FUNCTION, AND MUTAGENESIS OF LYS-358.
RX PubMed=30934824; DOI=10.3390/ijms20071574;
RA Vanwalscappel B., Gadea G., Despres P.;
RT "A Viperin Mutant Bearing the K358R Substitution Lost its Anti-ZIKA Virus
RT Activity.";
RL Int. J. Mol. Sci. 20:0-0(2019).
RN [27]
RP FUNCTION, ACETYLATION AT LYS-197, UBIQUITINATION AT LYS-206, AND
RP MUTAGENESIS OF LYS-197 AND LYS-206.
RX PubMed=31812350; DOI=10.1016/j.molcel.2019.11.003;
RA Yuan Y., Miao Y., Qian L., Zhang Y., Liu C., Liu J., Zuo Y., Feng Q.,
RA Guo T., Zhang L., Chen X., Jin L., Huang F., Zhang H., Zhang W., Li W.,
RA Xu G., Zheng H.;
RT "Targeting UBE4A Revives Viperin Protein in Epithelium to Enhance Host
RT Antiviral Defense.";
RL Mol. Cell 77:734-747(2020).
RN [28]
RP STRUCTURE BY NMR OF 45-361, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP COFACTOR.
RX PubMed=20026307; DOI=10.1016/j.bbrc.2009.12.070;
RA Shaveta G., Shi J., Chow V.T., Song J.;
RT "Structural characterization reveals that viperin is a radical S-adenosyl-
RT L-methionine (SAM) enzyme.";
RL Biochem. Biophys. Res. Commun. 391:1390-1395(2010).
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 (PubMed:31812350). Catalyzes the conversion of cytidine
CC triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) via a SAM-
CC dependent radical mechanism (PubMed:29925952, PubMed:30872404). In
CC turn, ddhCTP acts as a chain terminator for the RNA-dependent RNA
CC polymerases from multiple viruses and directly inhibits viral
CC replication (PubMed:29925952). Therefore, inhibits a wide range of DNA
CC and RNA viruses, including human cytomegalovirus (HCMV), hepatitis C
CC virus (HCV), west Nile virus (WNV), dengue virus, sindbis virus,
CC influenza A virus, sendai virus, vesicular stomatitis virus (VSV), zika
CC virus, and human immunodeficiency virus (HIV-1) (PubMed:29925952,
CC PubMed:30587778, PubMed:31921110, PubMed:30934824). Promotes also TLR7
CC and TLR9-dependent production of IFN-beta production in plasmacytoid
CC dendritic cells (pDCs) by facilitating 'Lys-63'-linked ubiquitination
CC of IRAK1 by TRAF6 (PubMed:30872404). Plays a role in CD4+ T-cells
CC activation and differentiation. Facilitates T-cell receptor (TCR)-
CC 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:0000269|PubMed:11752458,
CC ECO:0000269|PubMed:16108059, ECO:0000269|PubMed:16982913,
CC ECO:0000269|PubMed:17686841, ECO:0000269|PubMed:18005719,
CC ECO:0000269|PubMed:19074433, ECO:0000269|PubMed:29925952,
CC ECO:0000269|PubMed:30587778, ECO:0000269|PubMed:30872404,
CC ECO:0000269|PubMed:30934824, ECO:0000269|PubMed:31812350,
CC ECO:0000269|PubMed:31921110}.
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:0000269|PubMed:29925952,
CC ECO:0000269|PubMed:30872404};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:20026307, ECO:0000269|PubMed:20176015,
CC ECO:0000269|PubMed:22363738};
CC Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000269|PubMed:20026307, ECO:0000269|PubMed:20176015,
CC ECO:0000269|PubMed:22363738};
CC -!- ACTIVITY REGULATION: IRAK1 and TRAF6 synergistically activate RSAD2
CC increasing its activity with CTP as substrate about 10-fold.
CC {ECO:0000269|PubMed:30872404}.
CC -!- SUBUNIT: Homodimer. Interacts with IRAK1 and TRAF6 (PubMed:30872404,
CC PubMed:31921110). Interacts with FPPS (PubMed:18005724). Interacts with
CC HADHB (PubMed:21527675). Interacts (via C-terminus) with VAPA/VAP33
CC (via C-terminus) (PubMed:21957124). {ECO:0000269|PubMed:18005724,
CC ECO:0000269|PubMed:21527675, ECO:0000269|PubMed:21957124,
CC ECO:0000269|PubMed:30872404, ECO:0000269|PubMed:31921110}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human
CC cytomegalovirus/HHV-5 protein vMIA/UL37; this interaction results in
CC RSAD2/viperin relocalization from the endoplasmic reticulum to the
CC mitochondria. {ECO:0000269|PubMed:21527675}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via N-terminus) with
CC enterovirus A71 protein 2C; this interaction inhibits viral
CC replication. {ECO:0000269|PubMed:30587778}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus
CC 1/HHV-1 glycoprotein D; this interaction inhibits HHV-1 replication by
CC facilitating IRF7-mediated IFN-beta production.
CC {ECO:0000269|PubMed:31921110}.
CC -!- INTERACTION:
CC Q8WXG1; P02654: APOC1; NbExp=3; IntAct=EBI-12736320, EBI-1220105;
CC Q8WXG1; P55056: APOC4; NbExp=3; IntAct=EBI-12736320, EBI-18302142;
CC Q8WXG1; O76071: CIAO1; NbExp=2; IntAct=EBI-12736320, EBI-725145;
CC Q8WXG1; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-12736320, EBI-17589229;
CC Q8WXG1; Q9P0L0: VAPA; NbExp=10; IntAct=EBI-12736320, EBI-1059156;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein; Cytoplasmic side. Golgi apparatus
CC {ECO:0000269|PubMed:11752458, ECO:0000269|PubMed:16982913,
CC ECO:0000269|PubMed:31921110}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:11752458, ECO:0000269|PubMed:16982913,
CC ECO:0000269|PubMed:30587778}. Lipid droplet
CC {ECO:0000269|PubMed:31921110}. Mitochondrion. Mitochondrion inner
CC membrane. Mitochondrion outer membrane. Note=Infection with human
CC cytomegalovirus (HCMV) causes relocation to the Golgi apparatus and to
CC cytoplasmic vacuoles which also contain HCMV proteins glycoprotein B
CC and pp28. Interaction with human cytomegalovirus/HHV-5 protein
CC vMIA/UL37 results in its relocalization from the endoplasmic reticulum
CC to the mitochondria.
CC -!- INDUCTION: By interferon type I, type II and bacterial
CC lipopolysaccharides (LPS). Little or no induction by IFNG/IFN-gamma is
CC observed in monocytic cell lines. Induced by infection with hepatitis C
CC virus, yellow fever virus and Sendai virus, presumably through type I
CC interferon pathway. Induction by infection with human cytomegalovirus
CC (HCMV), stomatitis virus (VSV), chikungunya virus (CHIKV), Japanese
CC encephalitis virus (JEV) occurs independent of the IFN pathway.
CC {ECO:0000269|PubMed:11752458, ECO:0000269|PubMed:16108059,
CC ECO:0000269|PubMed:16150475, ECO:0000269|PubMed:16849320,
CC ECO:0000269|PubMed:9391139}.
CC -!- DOMAIN: The N-terminal region (1-42) is necessary for its localization
CC to the endoplasmic reticulum membrane and lipid droplet.
CC -!- PTM: Acetylated by HAT1. HAT1-mediated acetylation of Lys-197 in turn
CC recruits UBE4A that stimulates RSAD2 polyubiquitination leading to
CC proteasomal degradation. {ECO:0000269|PubMed:31812350}.
CC -!- PTM: 'Lys-6'-linked polyubiquitination at Lys-206 leads to RSAD2
CC protein degradation. {ECO:0000269|PubMed:31812350}.
CC -!- MISCELLANEOUS: Up-regulated in atherosclerosis. Latent viruses like
CC HCMV may be involved in atherogenesis by initiating local inflammation.
CC This may induce up-regulation of antiviral gene RSAD2, which modulates
CC lipids synthesis, and thus could play a role in abnormal lipid
CC accumulation leading to atherosclerosis.
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; AF026941; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF442151; AAL50053.1; -; mRNA.
DR EMBL; AC017076; AAY14802.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX01034.1; -; Genomic_DNA.
DR EMBL; BC017969; AAH17969.1; -; mRNA.
DR CCDS; CCDS1656.1; -.
DR RefSeq; NP_542388.2; NM_080657.4.
DR RefSeq; XP_011508716.1; XM_011510414.2.
DR AlphaFoldDB; Q8WXG1; -.
DR SMR; Q8WXG1; -.
DR BioGRID; 124843; 26.
DR IntAct; Q8WXG1; 11.
DR STRING; 9606.ENSP00000371471; -.
DR iPTMnet; Q8WXG1; -.
DR PhosphoSitePlus; Q8WXG1; -.
DR BioMuta; RSAD2; -.
DR DMDM; 74724033; -.
DR jPOST; Q8WXG1; -.
DR MassIVE; Q8WXG1; -.
DR PaxDb; Q8WXG1; -.
DR PeptideAtlas; Q8WXG1; -.
DR PRIDE; Q8WXG1; -.
DR ProteomicsDB; 75031; -.
DR Antibodypedia; 12336; 205 antibodies from 32 providers.
DR DNASU; 91543; -.
DR Ensembl; ENST00000382040.4; ENSP00000371471.3; ENSG00000134321.13.
DR Ensembl; ENST00000680607.1; ENSP00000506390.1; ENSG00000134321.13.
DR GeneID; 91543; -.
DR KEGG; hsa:91543; -.
DR MANE-Select; ENST00000382040.4; ENSP00000371471.3; NM_080657.5; NP_542388.2.
DR UCSC; uc002qyp.2; human.
DR CTD; 91543; -.
DR DisGeNET; 91543; -.
DR GeneCards; RSAD2; -.
DR HGNC; HGNC:30908; RSAD2.
DR HPA; ENSG00000134321; Tissue enhanced (salivary).
DR MIM; 607810; gene.
DR neXtProt; NX_Q8WXG1; -.
DR OpenTargets; ENSG00000134321; -.
DR PharmGKB; PA134937442; -.
DR VEuPathDB; HostDB:ENSG00000134321; -.
DR eggNOG; ENOG502QQMH; Eukaryota.
DR GeneTree; ENSGT00390000013670; -.
DR HOGENOM; CLU_049058_2_1_1; -.
DR InParanoid; Q8WXG1; -.
DR OMA; FRWKCFQ; -.
DR OrthoDB; 1098093at2759; -.
DR PhylomeDB; Q8WXG1; -.
DR TreeFam; TF300085; -.
DR PathwayCommons; Q8WXG1; -.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; Q8WXG1; -.
DR SIGNOR; Q8WXG1; -.
DR BioGRID-ORCS; 91543; 5 hits in 1073 CRISPR screens.
DR ChiTaRS; RSAD2; human.
DR GenomeRNAi; 91543; -.
DR Pharos; Q8WXG1; Tbio.
DR PRO; PR:Q8WXG1; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8WXG1; protein.
DR Bgee; ENSG00000134321; Expressed in buccal mucosa cell and 186 other tissues.
DR ExpressionAtlas; Q8WXG1; baseline and differential.
DR Genevisible; Q8WXG1; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
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; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA: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; IDA: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; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0050709; P:negative regulation of protein secretion; IDA:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
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; IDA: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; Atherosclerosis;
KW Endoplasmic reticulum; Golgi apparatus; Host-virus interaction; Immunity;
KW Innate immunity; Iron; Iron-sulfur; Isopeptide bond; Lipid droplet; Lyase;
KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Mitochondrion outer membrane; Reference proteome; S-adenosyl-L-methionine;
KW Ubl conjugation.
FT CHAIN 1..361
FT /note="Radical S-adenosyl methionine domain-containing
FT protein 2"
FT /id="PRO_0000309583"
FT DOMAIN 69..289
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT BINDING 83
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000305|PubMed:22363738"
FT BINDING 87
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000305|PubMed:22363738"
FT BINDING 90
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000305|PubMed:22363738"
FT MOD_RES 197
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:31812350"
FT CROSSLNK 206
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:31812350"
FT VARIANT 42
FT /note="L -> R (in dbSNP:rs17851586)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_036980"
FT VARIANT 52
FT /note="V -> I (in dbSNP:rs2305257)"
FT /id="VAR_053974"
FT MUTAGEN 83
FT /note="C->A: Loss of ability to assemble an Fe-S cluster
FT and significant decrease in protein stability."
FT /evidence="ECO:0000269|PubMed:22363738"
FT MUTAGEN 87
FT /note="C->A: Loss of ability to assemble an Fe-S cluster
FT and significant decrease in protein stability."
FT /evidence="ECO:0000269|PubMed:22363738"
FT MUTAGEN 90
FT /note="C->A: Loss of ability to assemble an Fe-S cluster
FT and significant decrease in protein stability."
FT /evidence="ECO:0000269|PubMed:22363738"
FT MUTAGEN 197
FT /note="K->R: Loss of acetylation."
FT /evidence="ECO:0000269|PubMed:31812350"
FT MUTAGEN 206
FT /note="K->R: Loss of Lys-6-linked ubiquitination."
FT /evidence="ECO:0000269|PubMed:31812350"
FT MUTAGEN 358
FT /note="K->A: Complete loss of antiviral activity against
FT Zika virus."
FT /evidence="ECO:0000269|PubMed:30934824"
FT CONFLICT 13
FT /note="L -> F (in Ref. 1; AF026941)"
FT /evidence="ECO:0000305"
FT CONFLICT 216..217
FT /note="VA -> IP (in Ref. 1; AF026941)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 361 AA; 42170 MW; ED014743CE1568DF CRC64;
MWVLTPAAFA GKLLSVFRQP LSSLWRSLVP LFCWLRATFW LLATKRRKQQ LVLRGPDETK
EEEEDPPLPT TPTSVNYHFT RQCNYKCGFC FHTAKTSFVL PLEEAKRGLL LLKEAGMEKI
NFSGGEPFLQ DRGEYLGKLV RFCKVELRLP SVSIVSNGSL IRERWFQNYG EYLDILAISC
DSFDEEVNVL IGRGQGKKNH VENLQKLRRW CRDYRVAFKI NSVINRFNVE EDMTEQIKAL
NPVRWKVFQC LLIEGENCGE DALREAERFV IGDEEFERFL ERHKEVSCLV PESNQKMKDS
YLILDEYMRF LNCRKGRKDP SKSILDVGVE EAIKFSGFDE KMFLKRGGKY IWSKADLKLD
W
