DCXR_HUMAN
ID DCXR_HUMAN Reviewed; 244 AA.
AC Q7Z4W1; Q9BTZ3; Q9UHY9;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=L-xylulose reductase;
DE Short=XR;
DE EC=1.1.1.10;
DE AltName: Full=Carbonyl reductase II;
DE AltName: Full=Dicarbonyl/L-xylulose reductase;
DE AltName: Full=Kidney dicarbonyl reductase;
DE Short=kiDCR;
DE AltName: Full=Short chain dehydrogenase/reductase family 20C member 1;
DE AltName: Full=Sperm surface protein P34H;
GN Name=DCXR; Synonyms=SDR20C1;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Epididymis;
RX PubMed=10385429; DOI=10.1210/endo.140.7.6791;
RA Legare C., Gaudreault C., St Jacques S., Sullivan R.;
RT "P34H sperm protein is preferentially expressed by the human corpus
RT epididymidis.";
RL Endocrinology 140:3318-3327(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, TISSUE SPECIFICITY, AND
RP INVOLVEMENT IN PNTSU.
RX PubMed=11882650; DOI=10.1074/jbc.m110703200;
RA Nakagawa J., Ishikura S., Asami J., Isaji T., Usami N., Hara A.,
RA Sakurai T., Tsuritani K., Oda K., Takahashi M., Yoshimoto M., Otsuka N.,
RA Kitamura K.;
RT "Molecular characterization of mammalian dicarbonyl/L-xylulose reductase
RT and its localization in kidney.";
RL J. Biol. Chem. 277:17883-17891(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Epididymis, Liver, and Testis;
RX PubMed=12680326;
RA Xia X.Y., Xu X.F., Gao Y., Huang Y.F.;
RT "Molecular cloning of human sperm surface protein P34H gene and semi-
RT quantitative analysis of its expression in testis and epididymidis.";
RL Zhonghua Nan Ke Xue 9:24-27(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal gland;
RA Huang C., Li Y., Wu T., Peng Y., Gu Y., Zhang L., Jiang C., Zhang C.,
RA Han Z., Wang Y., Chen Z., Fu G.;
RT "A novel gene expressed in the human adrenal gland.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liu Q., Yu L., Zhao S.Y.;
RT "Cloning and characterization of a new human cDNA of carbonyl reductase.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Placenta;
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 [8]
RP PROTEIN SEQUENCE OF 1-8, AND ACETYLATION AT MET-1.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP POSSIBLE INVOLVEMENT IN PNTSU.
RX PubMed=4392213; DOI=10.1056/nejm197004162821604;
RA Wang Y.M., Van Eys J.;
RT "The enzymatic defect in essential pentosuria.";
RL N. Engl. J. Med. 282:892-896(1970).
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 INVOLVEMENT IN PNTSU.
RX PubMed=22042873; DOI=10.1073/pnas.1115888108;
RA Pierce S.B., Spurrell C.H., Mandell J.B., Lee M.K., Zeligson S.,
RA Bereman M.S., Stray S.M., Fokstuen S., MacCoss M.J., Levy-Lahad E.,
RA King M.C., Motulsky A.G.;
RT "Garrod's fourth inborn error of metabolism solved by the identification of
RT mutations causing pentosuria.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:18313-18317(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-21, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS).
RX PubMed=12136162; DOI=10.1107/s0907444902008156;
RA El-Kabbani O., Chung R.P.-T., Ishikura S., Usami N., Nakagawa J., Hara A.;
RT "Crystallization and preliminary crystallographic analysis of human L-
RT xylulose reductase.";
RL Acta Crystallogr. D 58:1379-1380(2002).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) IN COMPLEX WITH NADP AND SUBSTRATE,
RP AND MUTAGENESIS OF ASN-107.
RX PubMed=15103634; DOI=10.1002/prot.20047;
RA El-Kabbani O., Ishikura S., Darmanin C., Carbone V., Chung R.P.-T.,
RA Usami N., Hara A.;
RT "Crystal structure of human L-xylulose reductase holoenzyme: probing the
RT role of Asn107 with site-directed mutagenesis.";
RL Proteins 55:724-732(2004).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of several pentoses,
CC tetroses, trioses, alpha-dicarbonyl compounds and L-xylulose.
CC Participates in the uronate cycle of glucose metabolism. May play a
CC role in the water absorption and cellular osmoregulation in the
CC proximal renal tubules by producing xylitol, an osmolyte, thereby
CC preventing osmolytic stress from occurring in the renal tubules.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + xylitol = H(+) + L-xylulose + NADPH;
CC Xref=Rhea:RHEA:17025, ChEBI:CHEBI:15378, ChEBI:CHEBI:17151,
CC ChEBI:CHEBI:17399, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.10;
CC Evidence={ECO:0000269|PubMed:11882650};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:15103634}.
CC -!- INTERACTION:
CC Q7Z4W1; Q7Z4W1: DCXR; NbExp=5; IntAct=EBI-1044712, EBI-1044712;
CC Q7Z4W1; Q9NS18: GLRX2; NbExp=3; IntAct=EBI-1044712, EBI-12102178;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Note=Probably recruited to membranes via an
CC interaction with phosphatidylinositol. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney, liver and epididymis.
CC In the epididymis, it is mainly expressed in the proximal and distal
CC sections of the corpus region. Weakly or not expressed in brain, lung,
CC heart, spleen and testis. {ECO:0000269|PubMed:10385429,
CC ECO:0000269|PubMed:11882650}.
CC -!- DISEASE: Pentosuria (PNTSU) [MIM:260800]: An inborn error of metabolism
CC characterized by excessive urinary excretion of L-xylulose.
CC {ECO:0000269|PubMed:11882650, ECO:0000269|PubMed:22042873,
CC ECO:0000269|PubMed:4392213}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {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; AB013846; BAB64299.1; -; mRNA.
DR EMBL; AF515623; AAN59786.1; -; mRNA.
DR EMBL; AF515624; AAO15991.1; -; mRNA.
DR EMBL; AF515625; AAM54026.1; -; mRNA.
DR EMBL; AF113123; AAF14864.1; -; mRNA.
DR EMBL; AF139841; AAP97273.1; -; mRNA.
DR EMBL; BT006881; AAP35527.1; -; mRNA.
DR EMBL; BC001470; AAH01470.1; -; mRNA.
DR EMBL; BC003018; AAH03018.1; -; mRNA.
DR CCDS; CCDS11799.1; -.
DR RefSeq; NP_001182147.1; NM_001195218.1.
DR RefSeq; NP_057370.1; NM_016286.3.
DR PDB; 1PR9; X-ray; 1.96 A; A/B=1-244.
DR PDB; 1WNT; X-ray; 2.30 A; A/B/C/D=1-244.
DR PDB; 3D3W; X-ray; 1.87 A; A/B=1-244.
DR PDBsum; 1PR9; -.
DR PDBsum; 1WNT; -.
DR PDBsum; 3D3W; -.
DR AlphaFoldDB; Q7Z4W1; -.
DR SMR; Q7Z4W1; -.
DR BioGRID; 119357; 72.
DR IntAct; Q7Z4W1; 15.
DR MINT; Q7Z4W1; -.
DR STRING; 9606.ENSP00000303356; -.
DR ChEMBL; CHEMBL2314; -.
DR DrugBank; DB02831; Dihydrogenphosphate.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR iPTMnet; Q7Z4W1; -.
DR PhosphoSitePlus; Q7Z4W1; -.
DR SwissPalm; Q7Z4W1; -.
DR BioMuta; DCXR; -.
DR DMDM; 50400451; -.
DR REPRODUCTION-2DPAGE; IPI00448095; -.
DR CPTAC; CPTAC-492; -.
DR CPTAC; CPTAC-493; -.
DR EPD; Q7Z4W1; -.
DR jPOST; Q7Z4W1; -.
DR MassIVE; Q7Z4W1; -.
DR MaxQB; Q7Z4W1; -.
DR PaxDb; Q7Z4W1; -.
DR PeptideAtlas; Q7Z4W1; -.
DR PRIDE; Q7Z4W1; -.
DR ProteomicsDB; 69250; -.
DR Antibodypedia; 19868; 351 antibodies from 33 providers.
DR DNASU; 51181; -.
DR Ensembl; ENST00000306869.7; ENSP00000303356.2; ENSG00000169738.8.
DR GeneID; 51181; -.
DR KEGG; hsa:51181; -.
DR MANE-Select; ENST00000306869.7; ENSP00000303356.2; NM_016286.4; NP_057370.1.
DR UCSC; uc002kdg.4; human.
DR CTD; 51181; -.
DR DisGeNET; 51181; -.
DR GeneCards; DCXR; -.
DR HGNC; HGNC:18985; DCXR.
DR HPA; ENSG00000169738; Tissue enriched (liver).
DR MalaCards; DCXR; -.
DR MIM; 260800; phenotype.
DR MIM; 608347; gene.
DR neXtProt; NX_Q7Z4W1; -.
DR OpenTargets; ENSG00000169738; -.
DR Orphanet; 2843; Pentosuria.
DR PharmGKB; PA38772; -.
DR VEuPathDB; HostDB:ENSG00000169738; -.
DR eggNOG; KOG1207; Eukaryota.
DR GeneTree; ENSGT00940000154873; -.
DR HOGENOM; CLU_010194_1_1_1; -.
DR InParanoid; Q7Z4W1; -.
DR OMA; GICEFKE; -.
DR OrthoDB; 1051625at2759; -.
DR PhylomeDB; Q7Z4W1; -.
DR TreeFam; TF313841; -.
DR BRENDA; 1.1.1.10; 2681.
DR PathwayCommons; Q7Z4W1; -.
DR Reactome; R-HSA-5661270; Formation of xylulose-5-phosphate.
DR Reactome; R-HSA-5662853; Essential pentosuria.
DR SABIO-RK; Q7Z4W1; -.
DR SignaLink; Q7Z4W1; -.
DR BioGRID-ORCS; 51181; 9 hits in 1080 CRISPR screens.
DR ChiTaRS; DCXR; human.
DR EvolutionaryTrace; Q7Z4W1; -.
DR GenomeRNAi; 51181; -.
DR Pharos; Q7Z4W1; Tbio.
DR PRO; PR:Q7Z4W1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q7Z4W1; protein.
DR Bgee; ENSG00000169738; Expressed in right lobe of liver and 195 other tissues.
DR ExpressionAtlas; Q7Z4W1; baseline and differential.
DR Genevisible; Q7Z4W1; HS.
DR GO; GO:0005903; C:brush border; IEA:Ensembl.
DR GO; GO:0005881; C:cytoplasmic microtubule; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050038; F:L-xylulose reductase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IDA:UniProtKB.
DR GO; GO:0042732; P:D-xylose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006006; P:glucose metabolic process; IDA:UniProtKB.
DR GO; GO:0006739; P:NADP metabolic process; IEA:Ensembl.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:UniProtKB.
DR GO; GO:0005997; P:xylulose metabolic process; IDA:UniProtKB.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Carbohydrate metabolism;
KW Direct protein sequencing; Glucose metabolism; Membrane; Methylation; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Xylose metabolism.
FT CHAIN 1..244
FT /note="L-xylulose reductase"
FT /id="PRO_0000054554"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT BINDING 11..40
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15103634"
FT BINDING 136
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15103634"
FT BINDING 153
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15103634"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 21
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MUTAGEN 107
FT /note="N->L,D: Loss of function. Probably due to defects in
FT formation of the active site and binding of coenzyme."
FT /evidence="ECO:0000269|PubMed:15103634"
FT CONFLICT 118
FT /note="V -> A (in Ref. 5; AAP97273)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="G -> R (in Ref. 1)"
FT /evidence="ECO:0000305"
FT STRAND 9..14
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:1PR9"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 41..50
FT /evidence="ECO:0007829|PDB:1PR9"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 64..71
FT /evidence="ECO:0007829|PDB:1PR9"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 97..107
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 109..125
FT /evidence="ECO:0007829|PDB:1PR9"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 147..167
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:1PR9"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 185..188
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 194..201
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 212..223
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:1PR9"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:1PR9"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:1PR9"
SQ SEQUENCE 244 AA; 25913 MW; F82B7A178D46EAA5 CRC64;
MELFLAGRRV LVTGAGKGIG RGTVQALHAT GARVVAVSRT QADLDSLVRE CPGIEPVCVD
LGDWEATERA LGSVGPVDLL VNNAAVALLQ PFLEVTKEAF DRSFEVNLRA VIQVSQIVAR
GLIARGVPGA IVNVSSQCSQ RAVTNHSVYC STKGALDMLT KVMALELGPH KIRVNAVNPT
VVMTSMGQAT WSDPHKAKTM LNRIPLGKFA EVEHVVNAIL FLLSDRSGMT TGSTLPVEGG
FWAC
