DUS2L_HUMAN
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 03-AUG-2022, entry version 162.
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; 9.
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; Q9NX74; -.
DR PeptideAtlas; Q9NX74; -.
DR PRIDE; Q9NX74; -.
DR ProteomicsDB; 83051; -.
DR Antibodypedia; 50008; 146 antibodies from 23 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 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; FRTCAQE; -.
DR OrthoDB; 801857at2759; -.
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 SignaLink; Q9NX74; -.
DR BioGRID-ORCS; 54920; 15 hits in 1069 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 162 other tissues.
DR ExpressionAtlas; Q9NX74; baseline and differential.
DR Genevisible; Q9NX74; HS.
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:0060548; P:negative regulation of cell death; IDA: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; 3.20.20.70; -; 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 Pfam; PF00035; dsrm; 1.
DR Pfam; PF01207; Dus; 1.
DR SMART; SM00358; DSRM; 1.
DR PROSITE; PS01136; UPF0034; 1.
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
