DUS4L_HUMAN
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 03-AUG-2022, entry version 149.
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 PRIDE; 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 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
