Reviewed, UniProtKB/Swiss-Prot Q7Z4W1 (DCXR_HUMAN)

Names and origin

Protein names

Recommended name:
    L-xylulose reductase
      Short name=XR
    EC=1.1.1.10
Alternative name(s):
    Dicarbonyl/L-xylulose reductase
    Kidney dicarbonyl reductase
      Short name=kiDCR
    Carbonyl reductase II
    Sperm surface protein P34H

Gene names

Name:

DCXR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	244 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the NADPH-dependent reduction of several pentoses, tetroses, trioses, alpha-dicarbonyl compounds and L-xylulose. Participates in the uronate cycle of glucose metabolism. May play a role in the water absorption and cellular osmoregulation in the proximal renal tubules by producing xylitol, an osmolyte, thereby preventing osmolytic stress from occurring in the renal tubules.
Catalytic activity	Xylitol + NADP(+) = L-xylulose + NADPH.
Subunit structure	Homotetramer.
Subcellular location	Membrane; Peripheral membrane proteinBy similarity. Note= Probably recruited to membranes via an interaction with phosphatidylinositol By similarity.
Tissue specificity	Highly expressed in kidney, liver and epididymis. In the epididymis, it is mainly expressed in the proximal and distal sections of the corpus region. Weakly or not expressed in brain, lung, heart, spleen and testis.
Involvement in disease	Defects in DCXR are a cause of pentosuria [MIM:260800]; also called L-xylulosuria or xylitol dehydrogenase deficiency. Pentosuria is an inborn error of carbohydrate metabolism, characterized by the excessive urinary excretion of the sugar xylitol.
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glucose metabolism Xylose metabolism
Cellular component	Membrane
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	D-xylose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW glucose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	L-xylulose reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 244

244

L-xylulose reductase

PRO_0000054554

Regions

Nucleotide binding

11 – 40

30

NADP

Sites

Active site

149

1

Proton acceptor

Binding site

136

1

Substrate

Binding site

153

1

NADP

Amino acid modifications

Modified residue

1

1

N-acetylmethionine

Modified residue

149

1

Phosphotyrosine

Experimental info

Mutagenesis

107

1

N → L or D: Loss of function. Probably due to defects in formation of the active site and binding of coenzyme

Sequence conflict

118

1

V → A in AAP97273. Ref.5

Sequence conflict

239

1

G → R Ref.1

Secondary structure

1

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244

Helix Strand Turn

Details...

Beta strand

9 – 14

6

Helix

18 – 29

12

Beta strand

33 – 39

7

Helix

41 – 50

10

Beta strand

55 – 58

4

Helix

64 – 71

8

Beta strand

79 – 82

4

Helix

92 – 94

3

Helix

97 – 107

11

Helix

109 – 125

17

Beta strand

129 – 134

6

Helix

137 – 139

3

Helix

147 – 167

21

Helix

168 – 170

3

Beta strand

172 – 179

8

Helix

185 – 188

4

Helix

194 – 201

8

Helix

212 – 223

12

Helix

225 – 227

3

Beta strand

234 – 238

5

Helix

241 – 243

3

Sequences

	Sequence		Length	Mass (Da)
	Q7Z4W1-1 [UniParc]. Last modified July 19, 2004. Version 2. Checksum: F82B7A178D46EAA5	FASTA	244	25,913
	10 20 30 40 50 60 MELFLAGRRV LVTGAGKGIG RGTVQALHAT GARVVAVSRT QADLDSLVRE CPGIEPVCVD 70 80 90 100 110 120 LGDWEATERA LGSVGPVDLL VNNAAVALLQ PFLEVTKEAF DRSFEVNLRA VIQVSQIVAR 130 140 150 160 170 180 GLIARGVPGA IVNVSSQCSQ RAVTNHSVYC STKGALDMLT KVMALELGPH KIRVNAVNPT 190 200 210 220 230 240 VVMTSMGQAT WSDPHKAKTM LNRIPLGKFA EVEHVVNAIL FLLSDRSGMT TGSTLPVEGG FWAC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"P34H sperm protein is preferentially expressed by the human corpus epididymidis." Legare C., Gaudreault C., St Jacques S., Sullivan R. Endocrinology 140:3318-3327(1999) [PubMed: 10385429] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Epididymis.
[2]	"Molecular characterization of mammalian dicarbonyl/L-xylulose reductase and its localization in kidney." Nakagawa J., Ishikura S., Asami J., Isaji T., Usami N., Hara A., Sakurai T., Tsuritani K., Oda K., Takahashi M., Yoshimoto M., Otsuka N., Kitamura K. J. Biol. Chem. 277:17883-17891(2002) [PubMed: 11882650] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, TISSUE SPECIFICITY, INVOLVEMENT IN PENTOSURIA.
[3]	"Molecular cloning of human sperm surface protein P34H gene and semi-quantitative analysis of its expression in testis and epididymidis." Xia X.Y., Xu X.F., Gao Y., Huang Y.F. Zhonghua Nan Ke Xue 9:24-27(2003) [PubMed: 12680326] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Epididymis, Liver and Testis.
[4]	"A novel gene expressed in the human adrenal gland." Huang C., Li Y., Wu T., Peng Y., Gu Y., Zhang L., Jiang C., Zhang C., Han Z., Wang Y., Chen Z., Fu G. Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adrenal gland.
[5]	"Cloning and characterization of a new human cDNA of carbonyl reductase." Liu Q., Yu L., Zhao S.Y. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Placenta.
[8]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-8, ACETYLATION AT MET-1. Tissue: Platelet.
[9]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-149, MASS SPECTROMETRY.
[10]	"Crystallization and preliminary crystallographic analysis of human L-xylulose reductase." El-Kabbani O., Chung R.P.-T., Ishikura S., Usami N., Nakagawa J., Hara A. Acta Crystallogr. D 58:1379-1380(2002) [PubMed: 12136162] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS).
[11]	"Crystal structure of human L-xylulose reductase holoenzyme: probing the role of Asn107 with site-directed mutagenesis." El-Kabbani O., Ishikura S., Darmanin C., Carbone V., Chung R.P.-T., Usami N., Hara A. Proteins 55:724-732(2004) [PubMed: 15103634] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) IN COMPLEX WITH NADP AND SUBSTRATE, MUTAGENESIS OF ASN-107.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB013846 mRNA. Translation: BAB64299.1.
AF515623 mRNA. Translation: AAN59786.1.
AF515624 mRNA. Translation: AAO15991.1.
AF515625 mRNA. Translation: AAM54026.1.
AF113123 mRNA. Translation: AAF14864.1.
AF139841 mRNA. Translation: AAP97273.1.
BT006881 mRNA. Translation: AAP35527.1.
BC001470 mRNA. Translation: AAH01470.1.
BC003018 mRNA. Translation: AAH03018.1.

RefSeq

NP_057370.1.

UniGene

Hs.9857

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PR9	X-ray	1.96	A/B	1-244	[»]
1WNT	X-ray	2.30	A/B/C/D	1-244	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q7Z4W1.

PTM databases

PhosphoSite

Q7Z4W1.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00448095.

Genome annotation databases

Ensembl

ENSG00000169738. Homo sapiens. [Contig view]

GeneID

51181.

KEGG

hsa:51181.

Organism-specific databases

H-InvDB

HIX0014266.

HGNC

HGNC:18985. DCXR.

MIM

260800. phenotype.
608347. gene.

PharmGKB

PA38772.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q7Z4W1.

HOVERGEN

Q7Z4W1.

Gene expression databases

ArrayExpress

Q7Z4W1.

CleanEx

HS_DCXR.

GermOnline

ENSG00000169738. Homo sapiens.

Family and domain databases

InterPro

IPR002198. DHase_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DHase.
IPR016040. NAD(P)-bd.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

PANTHER

PTHR19410. ADH_short_C2. 1 hit.

Pfam

PF00106. adh_short. 1 hit.
[Graphical view]

PRINTS

PR00081. GDHRDH.
PR00080. SDRFAMILY.

PROSITE

PS00061. ADH_SHORT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

54147.

SOURCE

Search...

Entry information

Entry name

DCXR_HUMAN

Accession

Primary (citable) accession number: Q7Z4W1
Secondary accession number(s): Q9BTZ3, Q9UHY9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	July 19, 2004
Last modified:	November 4, 2008
This is version 54 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)