ID   DUS2L_HUMAN             Reviewed;         493 AA.
AC   Q9NX74; A8K3G3; Q4H4D9;
DT   16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 171.
DE   RecName: Full=tRNA-dihydrouridine(20) synthase [NAD(P)+]-like;
DE            EC=1.3.1.91 {ECO:0000269|PubMed:15994936, ECO:0000269|PubMed:26429968, ECO:0000269|PubMed:30149704, ECO:0000305|PubMed:34798057};
DE   AltName: Full=Dihydrouridine synthase 2;
DE   AltName: Full=Up-regulated in lung cancer protein 8;
DE            Short=URLC8;
DE   AltName: Full=tRNA-dihydrouridine synthase 2-like {ECO:0000303|PubMed:15994936};
DE            Short=hDUS2 {ECO:0000303|PubMed:15994936};
GN   Name=DUS2; Synonyms=DUS2L;
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], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP   LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH EPRS1.
RX   PubMed=15994936; DOI=10.1158/0008-5472.can-05-0600;
RA   Kato T., Daigo Y., Hayama S., Ishikawa N., Yamabuki T., Ito T.,
RA   Miyamoto M., Kondo S., Nakamura Y.;
RT   "A novel human tRNA-dihydrouridine synthase involved in pulmonary
RT   carcinogenesis.";
RL   Cancer Res. 65:5638-5646(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Gastric carcinoma;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA   Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA   Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA   Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA   Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA   Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA   Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA   Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA   Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA   Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA   Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA   Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA   Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA   Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA   Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA   Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA   Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA   DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA   Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA   Myers R.M., Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
RN   [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon;
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]
RP   FUNCTION, AND INTERACTION WITH PRKRA AND EIF2AK2.
RX   PubMed=18096616; DOI=10.1093/nar/gkm1129;
RA   Mittelstadt M., Frump A., Khuu T., Fowlkes V., Handy I., Patel C.V.,
RA   Patel R.C.;
RT   "Interaction of human tRNA-dihydrouridine synthase-2 with interferon-
RT   induced protein kinase PKR.";
RL   Nucleic Acids Res. 36:998-1008(2008).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, AND IDENTIFICATION BY
RP   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   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [10]
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   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445 AND SER-488, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and 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   [12]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=34798057; DOI=10.1016/j.molcel.2021.11.003;
RA   Finet O., Yague-Sanz C., Krueger L.K., Tran P., Migeot V., Louski M.,
RA   Nevers A., Rougemaille M., Sun J., Ernst F.G.M., Wacheul L., Wery M.,
RA   Morillon A., Dedon P., Lafontaine D.L.J., Hermand D.;
RT   "Transcription-wide mapping of dihydrouridine reveals that mRNA
RT   dihydrouridylation is required for meiotic chromosome segregation.";
RL   Mol. Cell 0:0-0(2021).
RN   [13] {ECO:0007744|PDB:4XP7}
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-340 IN COMPLEX WITH FMN, AND
RP   COFACTOR.
RX   PubMed=26143927; DOI=10.1107/s1399004715009220;
RA   Whelan F., Jenkins H.T., Griffiths S.C., Byrne R.T., Dodson E.J.,
RA   Antson A.A.;
RT   "From bacterial to human dihydrouridine synthase: automated structure
RT   determination.";
RL   Acta Crystallogr. D 71:1564-1571(2015).
RN   [14] {ECO:0007744|PDB:4WFS, ECO:0007744|PDB:4WFT}
RP   X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 338-450 IN COMPLEX WITH FMN,
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND DOMAIN.
RX   PubMed=26429968; DOI=10.1093/nar/gkv989;
RA   Bou-Nader C., Pecqueur L., Bregeon D., Kamah A., Guerineau V.,
RA   Golinelli-Pimpaneau B., Guimaraes B.G., Fontecave M., Hamdane D.;
RT   "An extended dsRBD is required for post-transcriptional modification in
RT   human tRNAs.";
RL   Nucleic Acids Res. 43:9446-9456(2015).
RN   [15] {ECO:0007744|PDB:6EZA, ECO:0007744|PDB:6EZB, ECO:0007744|PDB:6EZC}
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 14-333 OF MUTANTS LYS-294 AND
RP   LYS-305 IN COMPLEX WITH FMN, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP   DOMAIN, AND MUTAGENESIS OF GLU-294 AND GLN-305.
RX   PubMed=30149704; DOI=10.1021/acs.biochem.8b00584;
RA   Bou-Nader C., Bregeon D., Pecqueur L., Fontecave M., Hamdane D.;
RT   "Electrostatic Potential in the tRNA Binding Evolution of Dihydrouridine
RT   Synthases.";
RL   Biochemistry 57:5407-5414(2018).
RN   [16] {ECO:0007744|PDB:5OC4, ECO:0007744|PDB:5OC5, ECO:0007744|PDB:5OC6}
RP   X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 338-450 IN COMPLEX WITH
RP   DOUBLE-STRANDED RNA, AND MUTAGENESIS OF 361-ARG-ARG-362; GLN-367; LYS-371;
RP   MET-372; ARG-379; ARG-397; LYS-417; LYS-419 AND LYS-420.
RX   PubMed=30605527; DOI=10.1093/nar/gky1302;
RA   Bou-Nader C., Barraud P., Pecqueur L., Perez J., Velours C., Shepard W.,
RA   Fontecave M., Tisne C., Hamdane D.;
RT   "Molecular basis for transfer RNA recognition by the double-stranded RNA-
RT   binding domain of human dihydrouridine synthase 2.";
RL   Nucleic Acids Res. 47:3117-3126(2019).
CC   -!- FUNCTION: Dihydrouridine synthase. Catalyzes the NADPH-dependent
CC       synthesis of dihydrouridine, a modified base found in the D-loop of
CC       most tRNAs (PubMed:15994936, PubMed:26429968, PubMed:30149704,
CC       PubMed:34798057). Negatively regulates the activation of EIF2AK2/PKR
CC       (PubMed:18096616). {ECO:0000269|PubMed:15994936,
CC       ECO:0000269|PubMed:18096616, ECO:0000269|PubMed:26429968,
CC       ECO:0000269|PubMed:30149704, ECO:0000269|PubMed:34798057}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5,6-dihydrouridine(20) in tRNA + NADP(+) = H(+) + NADPH +
CC         uridine(20) in tRNA; Xref=Rhea:RHEA:53336, Rhea:RHEA-COMP:13533,
CC         Rhea:RHEA-COMP:13534, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:65315, ChEBI:CHEBI:74443; EC=1.3.1.91;
CC         Evidence={ECO:0000269|PubMed:26429968, ECO:0000269|PubMed:30149704,
CC         ECO:0000305|PubMed:34798057};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53338;
CC         Evidence={ECO:0000269|PubMed:26429968, ECO:0000269|PubMed:30149704,
CC         ECO:0000305|PubMed:34798057};
CC   -!- COFACTOR:
CC       Name=FMN; Xref=ChEBI:CHEBI:58210;
CC         Evidence={ECO:0000269|PubMed:26143927, ECO:0000269|PubMed:26429968,
CC         ECO:0000269|PubMed:30149704};
CC   -!- SUBUNIT: Interacts with EPRS1. Interacts (via DRBM domain) with PRKRA
CC       and EIF2AK2/PKR (via DRBM 1 domain). {ECO:0000269|PubMed:15994936,
CC       ECO:0000269|PubMed:18096616}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15994936}.
CC       Endoplasmic reticulum {ECO:0000269|PubMed:15994936}. Note=Mainly at the
CC       endoplasmic reticulum. {ECO:0000269|PubMed:15994936}.
CC   -!- TISSUE SPECIFICITY: Weak expression in heart, placenta and skeletal
CC       muscle. Up-regulated in most lung cancer cells (at protein level).
CC       {ECO:0000269|PubMed:15994936}.
CC   -!- DOMAIN: Efficient dihydrouridine synthesis requires the presence of
CC       both the catalytic domain and the C-terminal RNA-binding DRBM domain.
CC       {ECO:0000269|PubMed:26429968}.
CC   -!- SIMILARITY: Belongs to the Dus family. Dus2 subfamily. {ECO:0000305}.
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DR   EMBL; AB101210; BAE07219.1; -; mRNA.
DR   EMBL; AK000406; BAA91143.1; -; mRNA.
DR   EMBL; AK290578; BAF83267.1; -; mRNA.
DR   EMBL; AC130462; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471092; EAW83207.1; -; Genomic_DNA.
DR   EMBL; BC006527; AAH06527.1; -; mRNA.
DR   CCDS; CCDS10859.1; -.
DR   RefSeq; NP_001258691.1; NM_001271762.1.
DR   RefSeq; NP_001258692.1; NM_001271763.1.
DR   RefSeq; NP_060273.1; NM_017803.4.
DR   PDB; 4WFS; X-ray; 2.68 A; A=14-333.
DR   PDB; 4WFT; X-ray; 1.70 A; A/B/C=338-450.
DR   PDB; 4XP7; X-ray; 1.90 A; A=1-340.
DR   PDB; 5OC4; X-ray; 1.71 A; A=338-450.
DR   PDB; 5OC5; X-ray; 1.89 A; A=338-450.
DR   PDB; 5OC6; X-ray; 3.20 A; A=338-450.
DR   PDB; 6EI8; X-ray; 2.25 A; A=338-450.
DR   PDB; 6EZA; X-ray; 2.00 A; A/B=14-333.
DR   PDB; 6EZB; X-ray; 2.25 A; A=14-333.
DR   PDB; 6EZC; X-ray; 2.00 A; A=14-333.
DR   PDB; 6F00; X-ray; 2.16 A; A/B/C=338-450.
DR   PDBsum; 4WFS; -.
DR   PDBsum; 4WFT; -.
DR   PDBsum; 4XP7; -.
DR   PDBsum; 5OC4; -.
DR   PDBsum; 5OC5; -.
DR   PDBsum; 5OC6; -.
DR   PDBsum; 6EI8; -.
DR   PDBsum; 6EZA; -.
DR   PDBsum; 6EZB; -.
DR   PDBsum; 6EZC; -.
DR   PDBsum; 6F00; -.
DR   AlphaFoldDB; Q9NX74; -.
DR   SMR; Q9NX74; -.
DR   BioGRID; 120261; 18.
DR   IntAct; Q9NX74; 12.
DR   MINT; Q9NX74; -.
DR   STRING; 9606.ENSP00000455229; -.
DR   BindingDB; Q9NX74; -.
DR   ChEMBL; CHEMBL3879825; -.
DR   iPTMnet; Q9NX74; -.
DR   MetOSite; Q9NX74; -.
DR   PhosphoSitePlus; Q9NX74; -.
DR   BioMuta; DUS2; -.
DR   DMDM; 73620832; -.
DR   EPD; Q9NX74; -.
DR   jPOST; Q9NX74; -.
DR   MassIVE; Q9NX74; -.
DR   MaxQB; Q9NX74; -.
DR   PaxDb; 9606-ENSP00000455229; -.
DR   PeptideAtlas; Q9NX74; -.
DR   ProteomicsDB; 83051; -.
DR   Pumba; Q9NX74; -.
DR   Antibodypedia; 50008; 173 antibodies from 24 providers.
DR   DNASU; 54920; -.
DR   Ensembl; ENST00000358896.10; ENSP00000351769.6; ENSG00000167264.18.
DR   Ensembl; ENST00000565263.6; ENSP00000455229.1; ENSG00000167264.18.
DR   GeneID; 54920; -.
DR   KEGG; hsa:54920; -.
DR   MANE-Select; ENST00000565263.6; ENSP00000455229.1; NM_017803.5; NP_060273.1.
DR   UCSC; uc002evi.5; human.
DR   AGR; HGNC:26014; -.
DR   CTD; 54920; -.
DR   DisGeNET; 54920; -.
DR   GeneCards; DUS2; -.
DR   HGNC; HGNC:26014; DUS2.
DR   HPA; ENSG00000167264; Low tissue specificity.
DR   MIM; 609707; gene.
DR   neXtProt; NX_Q9NX74; -.
DR   OpenTargets; ENSG00000167264; -.
DR   PharmGKB; PA142671937; -.
DR   VEuPathDB; HostDB:ENSG00000167264; -.
DR   eggNOG; KOG2334; Eukaryota.
DR   GeneTree; ENSGT00550000075019; -.
DR   InParanoid; Q9NX74; -.
DR   OMA; GPIRTNS; -.
DR   OrthoDB; 276273at2759; -.
DR   PhylomeDB; Q9NX74; -.
DR   TreeFam; TF106151; -.
DR   BRENDA; 1.3.1.91; 2681.
DR   PathwayCommons; Q9NX74; -.
DR   Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol.
DR   Reactome; R-HSA-9833482; PKR-mediated signaling.
DR   SignaLink; Q9NX74; -.
DR   BioGRID-ORCS; 54920; 18 hits in 1146 CRISPR screens.
DR   ChiTaRS; DUS2; human.
DR   GenomeRNAi; 54920; -.
DR   Pharos; Q9NX74; Tbio.
DR   PRO; PR:Q9NX74; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q9NX74; Protein.
DR   Bgee; ENSG00000167264; Expressed in granulocyte and 164 other cell types or tissues.
DR   ExpressionAtlas; Q9NX74; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0010181; F:FMN binding; IDA:UniProtKB.
DR   GO; GO:0070402; F:NADPH binding; IDA:UniProtKB.
DR   GO; GO:0004860; F:protein kinase inhibitor activity; IDA:UniProtKB.
DR   GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR   GO; GO:0017150; F:tRNA dihydrouridine synthase activity; IDA:UniProtKB.
DR   GO; GO:0102264; F:tRNA-dihydrouridine20 synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0140374; P:antiviral innate immune response; IPI:UniProtKB.
DR   GO; GO:0002943; P:tRNA dihydrouridine synthesis; IDA:UniProtKB.
DR   CDD; cd19871; DSRM_DUS2L; 1.
DR   CDD; cd02801; DUS_like_FMN; 1.
DR   Gene3D; 3.30.160.20; -; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR014720; dsRBD_dom.
DR   InterPro; IPR035587; DUS-like_FMN-bd.
DR   InterPro; IPR044463; DUS2_DSRM.
DR   InterPro; IPR018517; tRNA_hU_synthase_CS.
DR   PANTHER; PTHR45936; TRNA-DIHYDROURIDINE(20) SYNTHASE [NAD(P)+]-LIKE; 1.
DR   PANTHER; PTHR45936:SF1; TRNA-DIHYDROURIDINE(20) SYNTHASE [NAD(P)+]-LIKE; 1.
DR   Pfam; PF00035; dsrm; 1.
DR   Pfam; PF01207; Dus; 1.
DR   SMART; SM00358; DSRM; 1.
DR   SUPFAM; SSF54768; dsRNA-binding domain-like; 1.
DR   SUPFAM; SSF51395; FMN-linked oxidoreductases; 1.
DR   PROSITE; PS01136; UPF0034; 1.
DR   Genevisible; Q9NX74; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Endoplasmic reticulum; Flavoprotein; FMN; NADP;
KW   Oxidoreductase; Phosphoprotein; Reference proteome; RNA-binding;
KW   tRNA processing.
FT   CHAIN           1..493
FT                   /note="tRNA-dihydrouridine(20) synthase [NAD(P)+]-like"
FT                   /id="PRO_0000162157"
FT   DOMAIN          369..436
FT                   /note="DRBM"
FT                   /evidence="ECO:0000269|PubMed:26429968"
FT   REGION          1..333
FT                   /note="Catalytic domain"
FT                   /evidence="ECO:0000269|PubMed:26429968"
FT   REGION          330..349
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          367..371
FT                   /note="Interaction with tRNA"
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   REGION          420..424
FT                   /note="Interaction with tRNA"
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   REGION          438..493
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        330..346
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        443..460
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        116
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q5SMC7"
FT   BINDING         18..20
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:26143927,
FT                   ECO:0000269|PubMed:26429968, ECO:0007744|PDB:4WFS,
FT                   ECO:0007744|PDB:4XP7"
FT   BINDING         43
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:26143927,
FT                   ECO:0000269|PubMed:26429968, ECO:0007744|PDB:4WFS,
FT                   ECO:0007744|PDB:4XP7"
FT   BINDING         87
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:26143927,
FT                   ECO:0000269|PubMed:26429968, ECO:0007744|PDB:4WFS,
FT                   ECO:0007744|PDB:4XP7"
FT   BINDING         155
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:26143927,
FT                   ECO:0000269|PubMed:26429968, ECO:0007744|PDB:4WFS,
FT                   ECO:0007744|PDB:4XP7"
FT   BINDING         183
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:26429968,
FT                   ECO:0007744|PDB:4WFS"
FT   BINDING         214..216
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:26143927,
FT                   ECO:0000269|PubMed:26429968, ECO:0007744|PDB:4WFS,
FT                   ECO:0007744|PDB:4XP7"
FT   BINDING         242..243
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:26143927,
FT                   ECO:0000269|PubMed:26429968, ECO:0007744|PDB:4WFS,
FT                   ECO:0007744|PDB:4XP7"
FT   MOD_RES         445
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         488
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT   MUTAGEN         294
FT                   /note="E->K: Increased affinity for tRNA and increased
FT                   dihydrouridine synthesis; when associated with K-305."
FT                   /evidence="ECO:0000269|PubMed:30149704"
FT   MUTAGEN         305
FT                   /note="Q->K: Increased affinity for tRNA and increased
FT                   dihydrouridine synthesis; when associated with K-294."
FT                   /evidence="ECO:0000269|PubMed:30149704"
FT   MUTAGEN         361..362
FT                   /note="RR->AA: Decreased affinity for tRNA."
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   MUTAGEN         367
FT                   /note="Q->A: Mildly decreased affinity for tRNA."
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   MUTAGEN         371
FT                   /note="K->A: Strongly decreased affinity for tRNA."
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   MUTAGEN         372
FT                   /note="M->A: Mildly decreased affinity for tRNA."
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   MUTAGEN         379
FT                   /note="R->A: Mildly decreased affinity for tRNA."
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   MUTAGEN         397
FT                   /note="R->A: Mildly decreased affinity for tRNA."
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   MUTAGEN         417
FT                   /note="K->A: Mildly decreased affinity for tRNA."
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   MUTAGEN         419
FT                   /note="K->A: Decreased affinity for tRNA. Strongly
FT                   decreased affinity for tRNA; when associated with A-420."
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   MUTAGEN         420
FT                   /note="K->A: Decreased affinity for tRNA. Strongly
FT                   decreased affinity for tRNA; when associated with A-419."
FT                   /evidence="ECO:0000269|PubMed:30605527"
FT   STRAND          14..16
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   TURN            20..23
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           25..33
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          37..40
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           46..49
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          53..57
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   TURN            58..61
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          62..66
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          72..76
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           78..80
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   TURN            81..83
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          84..89
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           93..103
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           104..106
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          108..113
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           130..132
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           134..147
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          152..158
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           162..173
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   TURN            174..176
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          178..186
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           197..206
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          211..214
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   TURN            218..220
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          221..223
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           224..234
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          237..242
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           243..247
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           249..252
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           260..273
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           278..288
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   TURN            289..291
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           296..303
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           307..313
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           317..333
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   HELIX           336..338
FT                   /evidence="ECO:0007829|PDB:4XP7"
FT   STRAND          351..355
FT                   /evidence="ECO:0007829|PDB:4WFT"
FT   HELIX           361..363
FT                   /evidence="ECO:0007829|PDB:4WFT"
FT   HELIX           370..380
FT                   /evidence="ECO:0007829|PDB:4WFT"
FT   STRAND          387..393
FT                   /evidence="ECO:0007829|PDB:4WFT"
FT   HELIX           394..396
FT                   /evidence="ECO:0007829|PDB:4WFT"
FT   STRAND          398..405
FT                   /evidence="ECO:0007829|PDB:4WFT"
FT   STRAND          408..414
FT                   /evidence="ECO:0007829|PDB:4WFT"
FT   STRAND          416..418
FT                   /evidence="ECO:0007829|PDB:4WFT"
FT   HELIX           419..433
FT                   /evidence="ECO:0007829|PDB:4WFT"
SQ   SEQUENCE   493 AA;  55050 MW;  8CFE5046CCF79DCD CRC64;
     MILNSLSLCY HNKLILAPMV RVGTLPMRLL ALDYGADIVY CEELIDLKMI QCKRVVNEVL
     STVDFVAPDD RVVFRTCERE QNRVVFQMGT SDAERALAVA RLVENDVAGI DVNMGCPKQY
     STKGGMGAAL LSDPDKIEKI LSTLVKGTRR PVTCKIRILP SLEDTLSLVK RIERTGIAAI
     AVHGRKREER PQHPVSCEVI KAIADTLSIP VIANGGSHDH IQQYSDIEDF RQATAASSVM
     VARAAMWNPS IFLKEGLRPL EEVMQKYIRY AVQYDNHYTN TKYCLCQMLR EQLESPQGRL
     LHAAQSSREI CEAFGLGAFY EETTQELDAQ QARLSAKTSE QTGEPAEDTS GVIKMAVKFD
     RRAYPAQITP KMCLLEWCRR EKLAQPVYET VQRPLDRLFS SIVTVAEQKY QSTLWDKSKK
     LAEQAAAIVC LRSQGLPEGR LGEESPSLHK RKREAPDQDP GGPRAQELAQ PGDLCKKPFV
     ALGSGEESPL EGW
//