RIOK3_HUMAN
ID RIOK3_HUMAN Reviewed; 519 AA.
AC O14730; Q8IXN9;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Serine/threonine-protein kinase RIO3;
DE EC=2.7.11.1;
DE AltName: Full=RIO kinase 3;
DE AltName: Full=sudD homolog;
GN Name=RIOK3; Synonyms=SUDD;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9602165; DOI=10.1016/s0378-1119(98)00115-2;
RA Anaya P., Evans S.C., Dai C., Lozano G., May G.S.;
RT "Isolation of the Aspergillus nidulans sudD gene and its human homologue.";
RL Gene 211:323-329(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-122; SER-127 AND SER-128, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP FUNCTION, INTERACTION WITH CASP10, MUTAGENESIS OF LYS-290, AND
RP PHOSPHORYLATION.
RX PubMed=19557502; DOI=10.1007/s11010-009-0180-8;
RA Shan J., Wang P., Zhou J., Wu D., Shi H., Huo K.;
RT "RIOK3 interacts with caspase-10 and negatively regulates the NF-kappaB
RT signaling pathway.";
RL Mol. Cell. Biochem. 332:113-120(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP SUBUNIT.
RX PubMed=22072790; DOI=10.1091/mbc.e11-07-0639;
RA Widmann B., Wandrey F., Badertscher L., Wyler E., Pfannstiel J., Zemp I.,
RA Kutay U.;
RT "The kinase activity of human Rio1 is required for final steps of
RT cytoplasmic maturation of 40S subunits.";
RL Mol. Biol. Cell 23:22-35(2012).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=22418843; DOI=10.4161/rna.18810;
RA Baumas K., Soudet J., Caizergues-Ferrer M., Faubladier M., Henry Y.,
RA Mougin A.;
RT "Human RioK3 is a novel component of cytoplasmic pre-40S pre-ribosomal
RT particles.";
RL RNA Biol. 9:162-174(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8 AND SER-112, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP FUNCTION, INTERACTION WITH IRF3, AND MUTAGENESIS OF LYS-290.
RX PubMed=24807708; DOI=10.1128/jvi.00643-14;
RA Feng J., De Jesus P.D., Su V., Han S., Gong D., Wu N.C., Tian Y., Li X.,
RA Wu T.T., Chanda S.K., Sun R.;
RT "RIOK3 is an adaptor protein required for IRF3-mediated antiviral type I
RT interferon production.";
RL J. Virol. 88:7987-7997(2014).
RN [11]
RP FUNCTION.
RX PubMed=25865883; DOI=10.1016/j.celrep.2015.03.027;
RA Takashima K., Oshiumi H., Takaki H., Matsumoto M., Seya T.;
RT "RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and
RT attenuates the innate immune response.";
RL Cell Rep. 11:192-200(2015).
RN [12]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-336; GLN-441 AND LEU-447.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Involved in regulation of type I interferon (IFN)-dependent
CC immune response which plays a critical role in the innate immune
CC response against DNA and RNA viruses. May act as an adapter protein
CC essential for the recruitment of TBK1 to IRF3 (PubMed:24807708).
CC Phosphorylates IFIH1 on 'Ser-828' interfering with IFIH1 filament
CC assembly on long dsRNA and resulting in attenuated IFIH1-signaling
CC (PubMed:25865883). Can inhibit CASP10 isoform 7-mediated activation of
CC the NF-kappaB signaling pathway (PubMed:19557502). May play a role in
CC the biogenesis of the 40S ribosomal subunit. Involved in the processing
CC of 21S pre-rRNA to the mature 18S rRNA (PubMed:22418843).
CC {ECO:0000269|PubMed:19557502, ECO:0000269|PubMed:22418843,
CC ECO:0000269|PubMed:24807708, ECO:0000269|PubMed:25865883}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC -!- SUBUNIT: Interacts with CASP10 (PubMed:19557502). Interacts with IRF3;
CC RIOK3 probably mediates the interaction of TBK1 with IRF3
CC (PubMed:24807708). Associated with 40S pre-ribosomal particles.
CC {ECO:0000269|PubMed:19557502, ECO:0000269|PubMed:22072790,
CC ECO:0000269|PubMed:22418843}.
CC -!- INTERACTION:
CC O14730; Q92851: CASP10; NbExp=6; IntAct=EBI-1047061, EBI-495095;
CC O14730; Q92851-7: CASP10; NbExp=3; IntAct=EBI-1047061, EBI-12737837;
CC O14730; Q9BYX4: IFIH1; NbExp=6; IntAct=EBI-1047061, EBI-6115771;
CC O14730; Q14653: IRF3; NbExp=6; IntAct=EBI-1047061, EBI-2650369;
CC O14730; Q9UHD2: TBK1; NbExp=3; IntAct=EBI-1047061, EBI-356402;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22418843}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O14730-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14730-2; Sequence=VSP_012164;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9602165}.
CC -!- PTM: Autophosphorylated (in vitro). {ECO:0000269|PubMed:19557502}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. RIO-type Ser/Thr
CC kinase family. {ECO:0000305}.
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DR EMBL; AF013591; AAC26080.1; -; mRNA.
DR EMBL; AC026634; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC039729; AAH39729.1; -; mRNA.
DR CCDS; CCDS11877.1; -. [O14730-1]
DR RefSeq; NP_003822.2; NM_003831.4. [O14730-1]
DR AlphaFoldDB; O14730; -.
DR SMR; O14730; -.
DR BioGRID; 114309; 65.
DR IntAct; O14730; 19.
DR STRING; 9606.ENSP00000341874; -.
DR BindingDB; O14730; -.
DR ChEMBL; CHEMBL5659; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; O14730; -.
DR GlyGen; O14730; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O14730; -.
DR PhosphoSitePlus; O14730; -.
DR BioMuta; RIOK3; -.
DR EPD; O14730; -.
DR jPOST; O14730; -.
DR MassIVE; O14730; -.
DR MaxQB; O14730; -.
DR PaxDb; O14730; -.
DR PeptideAtlas; O14730; -.
DR PRIDE; O14730; -.
DR ProteomicsDB; 48188; -. [O14730-1]
DR ProteomicsDB; 48189; -. [O14730-2]
DR Antibodypedia; 967; 198 antibodies from 30 providers.
DR DNASU; 8780; -.
DR Ensembl; ENST00000339486.8; ENSP00000341874.3; ENSG00000101782.15. [O14730-1]
DR Ensembl; ENST00000577501.5; ENSP00000462548.1; ENSG00000101782.15. [O14730-2]
DR GeneID; 8780; -.
DR KEGG; hsa:8780; -.
DR MANE-Select; ENST00000339486.8; ENSP00000341874.3; NM_003831.5; NP_003822.2.
DR UCSC; uc002kui.5; human. [O14730-1]
DR CTD; 8780; -.
DR DisGeNET; 8780; -.
DR GeneCards; RIOK3; -.
DR HGNC; HGNC:11451; RIOK3.
DR HPA; ENSG00000101782; Tissue enhanced (bone).
DR MIM; 603579; gene.
DR neXtProt; NX_O14730; -.
DR OpenTargets; ENSG00000101782; -.
DR PharmGKB; PA36248; -.
DR VEuPathDB; HostDB:ENSG00000101782; -.
DR eggNOG; KOG2269; Eukaryota.
DR GeneTree; ENSGT00940000157008; -.
DR InParanoid; O14730; -.
DR OMA; IPRCGFK; -.
DR PhylomeDB; O14730; -.
DR TreeFam; TF105831; -.
DR PathwayCommons; O14730; -.
DR Reactome; R-HSA-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR SignaLink; O14730; -.
DR SIGNOR; O14730; -.
DR BioGRID-ORCS; 8780; 39 hits in 1115 CRISPR screens.
DR ChiTaRS; RIOK3; human.
DR GenomeRNAi; 8780; -.
DR Pharos; O14730; Tchem.
DR PRO; PR:O14730; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O14730; protein.
DR Bgee; ENSG00000101782; Expressed in jejunal mucosa and 210 other tissues.
DR ExpressionAtlas; O14730; baseline and differential.
DR Genevisible; O14730; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030688; C:preribosome, small subunit precursor; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0089720; F:caspase binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:1990786; P:cellular response to dsDNA; IMP:UniProtKB.
DR GO; GO:0071359; P:cellular response to dsRNA; IMP:UniProtKB.
DR GO; GO:0098586; P:cellular response to virus; IMP:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; TAS:ProtInc.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0030490; P:maturation of SSU-rRNA; IMP:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0039534; P:negative regulation of MDA-5 signaling pathway; IMP:UniProtKB.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000687; RIO_kinase.
DR InterPro; IPR018935; RIO_kinase_CS.
DR InterPro; IPR017406; Ser/Thr_kinase_Rio3.
DR PIRSF; PIRSF038146; Ser/Thr_PK_RIO3; 1.
DR SMART; SM00090; RIO; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01245; RIO1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiviral defense; ATP-binding; Cytoplasm; Immunity;
KW Innate immunity; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Ribosome biogenesis;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..519
FT /note="Serine/threonine-protein kinase RIO3"
FT /id="PRO_0000213529"
FT DOMAIN 251..519
FT /note="Protein kinase"
FT REGION 121..159
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 406
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 257..265
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 290
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 122
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 125
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBU3"
FT MOD_RES 127
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 449..451
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012164"
FT VARIANT 336
FT /note="L -> V (in dbSNP:rs35401850)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042355"
FT VARIANT 441
FT /note="R -> Q (in dbSNP:rs33969048)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042356"
FT VARIANT 447
FT /note="S -> L (in dbSNP:rs56282762)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042357"
FT MUTAGEN 290
FT /note="K->A: Decreases autophosphorylation (in vitro);
FT abolishes inhibition of TNF-alpha-induced NF-kappaB
FT activation; no effect on interaction with IRF3; fails to
FT activate IFN-beta promoter and IRF3 phosphorylation."
FT /evidence="ECO:0000269|PubMed:19557502,
FT ECO:0000269|PubMed:24807708"
FT CONFLICT 325
FT /note="I -> H (in Ref. 1; AAC26080)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 59093 MW; 3C3392BAC4ECB912 CRC64;
MDLVGVASPE PGTAAAWGPS KCPWAIPQNT ISCSLADVMS EQLAKELQLE EEAAVFPEVA
VAEGPFITGE NIDTSSDLML AQMLQMEYDR EYDAQLRREE KKFNGDSKVS ISFENYRKVH
PYEDSDSSED EVDWQDTRDD PYRPAKPVPT PKKGFIGKGK DITTKHDEVV CGRKNTARME
NFAPEFQVGD GIGMDLKLSN HVFNALKQHA YSEERRSARL HEKKEHSTAE KAVDPKTRLL
MYKMVNSGML ETITGCISTG KESVVFHAYG GSMEDEKEDS KVIPTECAIK VFKTTLNEFK
NRDKYIKDDF RFKDRFSKLN PRKIIRMWAE KEMHNLARMQ RAGIPCPTVV LLKKHILVMS
FIGHDQVPAP KLKEVKLNSE EMKEAYYQTL HLMRQLYHEC TLVHADLSEY NMLWHAGKVW
LIDVSQSVEP THPHGLEFLF RDCRNVSQFF QKGGVKEALS ERELFNAVSG LNITADNEAD
FLAEIEALEK MNEDHVQKNG RKAASFLKDD GDPPLLYDE
