DUS2L_MOUSE
ID DUS2L_MOUSE Reviewed; 493 AA.
AC Q9D7B1; Q6PDX2;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=tRNA-dihydrouridine(20) synthase [NAD(P)+]-like;
DE EC=1.3.1.91 {ECO:0000250|UniProtKB:Q9NX74};
DE AltName: Full=Dihydrouridine synthase 2;
DE AltName: Full=tRNA-dihydrouridine synthase 2-like;
GN Name=Dus2; Synonyms=Dus2l;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 205-493.
RC STRAIN=C57BL/6J; 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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP STRUCTURE BY NMR OF 350-464.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the DSRBD from hypothetical protein BAB26260.";
RL Submitted (NOV-2004) to the PDB data bank.
CC -!- FUNCTION: Dihydrouridine synthase. Catalyzes the NADPH-dependent
CC synthesis of dihydrouridine, a modified base found in the D-loop of
CC most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.
CC {ECO:0000250|UniProtKB:Q9NX74}.
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:0000250|UniProtKB:Q9NX74};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53338;
CC Evidence={ECO:0000250|UniProtKB:Q9NX74};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q9NX74};
CC -!- SUBUNIT: Interacts with EPRS1. Interacts (via DRBM domain) with PRKRA
CC and EIF2AK2/PKR (via DRBM 1 domain). {ECO:0000250|UniProtKB:Q9NX74}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9NX74}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q9NX74}. Note=Mainly at
CC the endoplasmic reticulum. {ECO:0000250|UniProtKB:Q9NX74}.
CC -!- DOMAIN: Efficient dihydrouridine synthesis requires the presence of
CC both the catalytic domain and the C-terminal RNA-binding DRBM domain.
CC {ECO:0000250|UniProtKB:Q9NX74}.
CC -!- SIMILARITY: Belongs to the Dus family. Dus2 subfamily. {ECO:0000305}.
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DR EMBL; AK009391; BAB26260.1; -; mRNA.
DR EMBL; BC058431; AAH58431.1; -; mRNA.
DR CCDS; CCDS22627.1; -.
DR RefSeq; NP_001288105.1; NM_001301176.1.
DR RefSeq; NP_079794.1; NM_025518.4.
DR RefSeq; XP_006531341.1; XM_006531278.3.
DR PDB; 1WHN; NMR; -; A=350-464.
DR PDBsum; 1WHN; -.
DR AlphaFoldDB; Q9D7B1; -.
DR BMRB; Q9D7B1; -.
DR SMR; Q9D7B1; -.
DR STRING; 10090.ENSMUSP00000034375; -.
DR iPTMnet; Q9D7B1; -.
DR PhosphoSitePlus; Q9D7B1; -.
DR EPD; Q9D7B1; -.
DR MaxQB; Q9D7B1; -.
DR PaxDb; Q9D7B1; -.
DR PRIDE; Q9D7B1; -.
DR ProteomicsDB; 279583; -.
DR Antibodypedia; 50008; 146 antibodies from 23 providers.
DR Ensembl; ENSMUST00000034375; ENSMUSP00000034375; ENSMUSG00000031901.
DR GeneID; 66369; -.
DR KEGG; mmu:66369; -.
DR UCSC; uc009nfa.2; mouse.
DR CTD; 54920; -.
DR MGI; MGI:1913619; Dus2.
DR VEuPathDB; HostDB:ENSMUSG00000031901; -.
DR eggNOG; KOG2334; Eukaryota.
DR GeneTree; ENSGT00550000075019; -.
DR HOGENOM; CLU_013299_3_0_1; -.
DR InParanoid; Q9D7B1; -.
DR OMA; FRTCAQE; -.
DR OrthoDB; 801857at2759; -.
DR PhylomeDB; Q9D7B1; -.
DR TreeFam; TF106151; -.
DR BioGRID-ORCS; 66369; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Dus2; mouse.
DR EvolutionaryTrace; Q9D7B1; -.
DR PRO; PR:Q9D7B1; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9D7B1; protein.
DR Bgee; ENSMUSG00000031901; Expressed in otolith organ and 215 other tissues.
DR ExpressionAtlas; Q9D7B1; baseline and differential.
DR Genevisible; Q9D7B1; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0010181; F:FMN binding; ISS:UniProtKB.
DR GO; GO:0070402; F:NADPH binding; ISS:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR GO; GO:0017150; F:tRNA dihydrouridine synthase activity; ISS:UniProtKB.
DR GO; GO:0102264; F:tRNA-dihydrouridine20 synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0060548; P:negative regulation of cell death; ISS:UniProtKB.
DR GO; GO:0002943; P:tRNA dihydrouridine synthesis; ISS: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;
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_0000162158"
FT DOMAIN 369..436
FT /note="DRBM"
FT REGION 1..333
FT /note="Catalytic domain"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT REGION 367..371
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT REGION 420..424
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT REGION 438..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..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:0000250|UniProtKB:Q9NX74"
FT BINDING 43
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT BINDING 87
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT BINDING 155
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT BINDING 183
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT BINDING 214..216
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT BINDING 242..243
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NX74"
FT STRAND 349..355
FT /evidence="ECO:0007829|PDB:1WHN"
FT HELIX 361..363
FT /evidence="ECO:0007829|PDB:1WHN"
FT HELIX 370..380
FT /evidence="ECO:0007829|PDB:1WHN"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:1WHN"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:1WHN"
FT STRAND 399..405
FT /evidence="ECO:0007829|PDB:1WHN"
FT STRAND 408..414
FT /evidence="ECO:0007829|PDB:1WHN"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:1WHN"
FT HELIX 419..434
FT /evidence="ECO:0007829|PDB:1WHN"
FT STRAND 437..439
FT /evidence="ECO:0007829|PDB:1WHN"
FT TURN 440..442
FT /evidence="ECO:0007829|PDB:1WHN"
SQ SEQUENCE 493 AA; 55325 MW; B66BDCB06B096299 CRC64;
MIVNSLSLCY HNKLILAPMV RVGTLPMRLL ALDYGADIVY CEELIDLKML QCKRVVNEVL
STVDFVAPDD RVVFRTCERE QSRVVFQMGT SDAERALAVA RLVENDVAGI DVNMGCPKEY
STKGGMGAAL LSDPDKIEKI LSTLVKGTHR PVTCKIRILP SLEDTLNLVK RIERTGISAI
AVHGRNRDER PQHPVSCEVI RAIAETLSIP VIANGGSHDH IQQHVDIEDF RQATAASSVM
VARAAMWNPS IFLKDGLRPL EEVMQKYIRY AVQYDNHYTN TKYCLCQMLR EQLESPQGRL
LHAAQSSQEI CEAFGLGAFY EETIRELDAR RADLLAKTPE AVEEPAEDTS GIIKMAIRFD
RRAYPPQITP KMCLLEWCRR EKLPQPVYET VQRTIDRMFC SVVTVAEQKY QSTLWDKSKK
LAEQTAAIVC LRSQGLPEGR LGEESPSLNK RKREAPDQDP GGPRVQEPAL PGEICKKPFV
TLDSSEENLL EGC
