ID DUS4L_HUMAN Reviewed; 317 AA. AC O95620; B4DLX0; Q2NKK1; DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 25-JUL-2006, sequence version 2. DT 14-DEC-2022, entry version 150. DE RecName: Full=tRNA-dihydrouridine(20a/20b) synthase [NAD(P)+]-like; DE EC=1.3.1.90 {ECO:0000305|PubMed:34798057}; DE AltName: Full=pp35; DE AltName: Full=tRNA-dihydrouridine synthase 4-like; GN Name=DUS4L; 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). RC TISSUE=Placenta; RA Laustsen P.G., Kristensen T.; RT "The gene encoding a human placental cDNA homologous with the E.coli yhdg RT and R. capsulatus nifR3 genes is located on chromosome 7."; RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; 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]. 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [5] 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). CC -!- FUNCTION: Catalyzes the synthesis of dihydrouridine, a modified base CC found in the D-loop of most tRNAs. {ECO:0000269|PubMed:34798057}. CC -!- CATALYTIC ACTIVITY: CC Reaction=5,6-dihydrouridine(20a) in tRNA + NADP(+) = H(+) + NADPH + CC uridine(20a) in tRNA; Xref=Rhea:RHEA:53344, Rhea:RHEA-COMP:13535, CC Rhea:RHEA-COMP:13536, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:65315, ChEBI:CHEBI:74443; EC=1.3.1.90; CC Evidence={ECO:0000305|PubMed:34798057}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53346; CC Evidence={ECO:0000305|PubMed:34798057}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5,6-dihydrouridine(20a) in tRNA + NAD(+) = H(+) + NADH + CC uridine(20a) in tRNA; Xref=Rhea:RHEA:53348, Rhea:RHEA-COMP:13535, CC Rhea:RHEA-COMP:13536, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:65315, ChEBI:CHEBI:74443; EC=1.3.1.90; CC Evidence={ECO:0000305|PubMed:34798057}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53350; CC Evidence={ECO:0000305|PubMed:34798057}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5,6-dihydrouridine(20b) in tRNA + NAD(+) = H(+) + NADH + CC uridine(20b) in tRNA; Xref=Rhea:RHEA:53352, Rhea:RHEA-COMP:13537, CC Rhea:RHEA-COMP:13538, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:65315, ChEBI:CHEBI:74443; EC=1.3.1.90; CC Evidence={ECO:0000250|UniProtKB:Q06063}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53354; CC Evidence={ECO:0000250|UniProtKB:Q06063}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5,6-dihydrouridine(20b) in tRNA + NADP(+) = H(+) + NADPH + CC uridine(20b) in tRNA; Xref=Rhea:RHEA:53356, Rhea:RHEA-COMP:13537, CC Rhea:RHEA-COMP:13538, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:65315, ChEBI:CHEBI:74443; EC=1.3.1.90; CC Evidence={ECO:0000250|UniProtKB:Q06063}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53358; CC Evidence={ECO:0000250|UniProtKB:Q06063}; CC -!- COFACTOR: CC Name=FMN; Xref=ChEBI:CHEBI:58210; CC Evidence={ECO:0000250|UniProtKB:Q5SMC7}; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O95620-1; Sequence=Displayed; CC Name=2; CC IsoId=O95620-2; Sequence=VSP_019975; CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the Dus family. Dus4 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD00100.1; Type=Frameshift; Evidence={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; U62767; AAD00100.1; ALT_FRAME; mRNA. DR EMBL; AK297195; BAG59682.1; -; mRNA. DR EMBL; CH471070; EAW83400.1; -; Genomic_DNA. DR EMBL; BC111774; AAI11775.1; -; mRNA. DR CCDS; CCDS5745.1; -. [O95620-1] DR RefSeq; NP_001257348.1; NM_001270419.1. [O95620-1] DR RefSeq; NP_853559.1; NM_181581.2. [O95620-1] DR RefSeq; XP_005250182.1; XM_005250125.4. DR RefSeq; XP_011514068.1; XM_011515766.2. DR RefSeq; XP_011514069.1; XM_011515767.2. DR RefSeq; XP_016867197.1; XM_017011708.1. DR AlphaFoldDB; O95620; -. DR SMR; O95620; -. DR BioGRID; 116246; 10. DR IntAct; O95620; 5. DR STRING; 9606.ENSP00000265720; -. DR iPTMnet; O95620; -. DR PhosphoSitePlus; O95620; -. DR BioMuta; DUS4L; -. DR EPD; O95620; -. DR jPOST; O95620; -. DR MassIVE; O95620; -. DR MaxQB; O95620; -. DR PaxDb; O95620; -. DR PeptideAtlas; O95620; -. DR ProteomicsDB; 50952; -. [O95620-1] DR ProteomicsDB; 50953; -. [O95620-2] DR Antibodypedia; 48607; 138 antibodies from 20 providers. DR DNASU; 11062; -. DR Ensembl; ENST00000265720.8; ENSP00000265720.3; ENSG00000105865.11. [O95620-1] DR Ensembl; ENST00000639937.2; ENSP00000491438.1; ENSG00000284103.2. [O95620-1] DR GeneID; 11062; -. DR KEGG; hsa:11062; -. DR MANE-Select; ENST00000265720.8; ENSP00000265720.3; NM_181581.3; NP_853559.1. DR UCSC; uc003veh.5; human. [O95620-1] DR AGR; HGNC:21517; -. DR CTD; 11062; -. DR DisGeNET; 11062; -. DR GeneCards; DUS4L; -. DR HGNC; HGNC:21517; DUS4L. DR HPA; ENSG00000105865; Low tissue specificity. DR MalaCards; DUS4L; -. DR neXtProt; NX_O95620; -. DR OpenTargets; ENSG00000105865; -. DR PharmGKB; PA142671939; -. DR VEuPathDB; HostDB:ENSG00000105865; -. DR eggNOG; KOG2335; Eukaryota. DR GeneTree; ENSGT00550000074907; -. DR HOGENOM; CLU_013299_4_2_1; -. DR InParanoid; O95620; -. DR OMA; LIYPYVD; -. DR PhylomeDB; O95620; -. DR TreeFam; TF105618; -. DR PathwayCommons; O95620; -. DR SignaLink; O95620; -. DR BioGRID-ORCS; 11062; 10 hits in 1071 CRISPR screens. DR GenomeRNAi; 11062; -. DR Pharos; O95620; Tbio. DR PRO; PR:O95620; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; O95620; protein. DR Bgee; ENSG00000105865; Expressed in endometrium and 100 other tissues. DR ExpressionAtlas; O95620; baseline and differential. DR Genevisible; O95620; HS. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro. DR GO; GO:0017150; F:tRNA dihydrouridine synthase activity; IBA:GO_Central. DR GO; GO:0002943; P:tRNA dihydrouridine synthesis; IDA:UniProtKB. DR CDD; cd02801; DUS_like_FMN; 1. DR Gene3D; 3.20.20.70; -; 1. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR035587; DUS-like_FMN-bd. DR InterPro; IPR001269; DUS_fam. DR InterPro; IPR018517; tRNA_hU_synthase_CS. DR Pfam; PF01207; Dus; 1. DR PIRSF; PIRSF006621; Dus; 1. DR PROSITE; PS01136; UPF0034; 1. PE 1: Evidence at protein level; KW Alternative splicing; Flavoprotein; FMN; Oxidoreductase; KW Reference proteome; tRNA processing. FT CHAIN 1..317 FT /note="tRNA-dihydrouridine(20a/20b) synthase [NAD(P)+]- FT like" FT /id="PRO_0000247347" FT ACT_SITE 116 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:Q5SMC7" FT BINDING 33..35 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:Q5SMC7" FT BINDING 87 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:Q5SMC7" FT BINDING 158 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:Q5SMC7" FT BINDING 186 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:Q5SMC7" FT BINDING 216..218 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:Q5SMC7" FT BINDING 240..241 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:Q5SMC7" FT VAR_SEQ 1..121 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_019975" FT VARIANT 178 FT /note="T -> A (in dbSNP:rs6956789)" FT /id="VAR_048938" FT VARIANT 230 FT /note="R -> Q (in dbSNP:rs6957510)" FT /id="VAR_027094" FT CONFLICT 162 FT /note="H -> N (in Ref. 1; AAD00100)" FT /evidence="ECO:0000305" FT CONFLICT 210 FT /note="S -> C (in Ref. 1; AAD00100)" FT /evidence="ECO:0000305" SQ SEQUENCE 317 AA; 35816 MW; 52A8AF158275B3BF CRC64; MKSDCMQTTI CQERKKDPIE MFHSGQLVKV CAPMVRYSKL AFRTLVRKYS CDLCYTPMIV AADFVKSIKA RDSEFTTNQG DCPLIVQFAA NDARLLSDAA RIVCPYANGI DINCGCPQRW AMAEGYGACL INKPELVQDM VKQVRNQVET PGFSVSIKIR IHDDLKRTVD LCQKAEATGV SWITVHGRTA EERHQPVHYD SIKIIKENMS IPVIANGDIR SLKEAENVWR ITGTDGVMVA RGLLANPAMF AGYEETPLKC IWDWVDIALE LGTPYMCFHQ HLMYMMEKIT SRQEKRVFNA LSSTSAIIDY LTDHYGI //