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Q13268 (DHRS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dehydrogenase/reductase SDR family member 2, mitochondrial

EC=1.1.1.-
Alternative name(s):
Dicarbonyl reductase HEP27
Protein D
Gene names
Name:DHRS2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length280 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Displays NADPH-dependent dicarbonyl reductase activity in vitro with 3,4-Hexanedione, 2,3-Heptanedione and 1-Phenyl-1,2-propanedione as substrates. No reductase activity is displayed in vitro with steroids, retinoids and sugars as substrates. Attenuates MDM2-mediated p53/TP53 degradation, leading to p53/TP53 stabilization and increased transcription activity, resulting in the accumulation of MDM2 and CDKN1A/p21. Ref.9 Ref.10

Subunit structure

Directly interacts with MDM2; this interaction occurs in the nucleus and does not target DHRS2 to degradation. Ref.10

Subcellular location

Mitochondrion matrix. Nucleus. Note: A minor fraction of the protein is translocated from the mitochondria to the nucleus, after cleavage of the targeting signal. Ref.2 Ref.7 Ref.10

Tissue specificity

Widely expressed, with highest levels in liver and kidney, followed by heart, spleen, skeletal muscle and placenta. In hemopoietic cells, expressed in dendritic cells, but not in monocytes, macrophages, granulocytes, nor in B and T lymphocytes. Ref.8

Induction

Up-regulated by IL4 and CSF2 in monocytes/macrophages. Down-regulated by bacterial lipopolysaccharides (LPS) and TNF in monocytice-derived dendritic cells. Up-regulated by MYB. Ref.8

Sequence similarities

Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Biophysicochemical properties

Kinetic parameters:

KM=0.3 mM for 1-Phenyl-1,2-propanedione Ref.9

KM=1.1 mM for 2,3-Heptanedione

KM=0.8 mM for 3,4-Hexanedione

Vmax=0.52 mmol/min/mg enzyme with 1-Phenyl-1,2-propanedione as substrate

Vmax=0.64 mmol/min/mg enzyme with 2,3-Heptanedione as substrate

Vmax=0.35 mmol/min/mg enzyme with 3,4-Hexanedione as substrate

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13268-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q13268-2)

The sequence of this isoform differs from the canonical sequence as follows:
     226-280: FHGNESLWKN...IAVAGYSTRL → VRIGFMGMSL...CVAVVPGPGA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2323Mitochondrion Ref.1
Chain24 – 280257Dehydrogenase/reductase SDR family member 2, mitochondrial
PRO_0000054642

Regions

Nucleotide binding40 – 6425NAD or NADP By similarity

Sites

Active site1851Proton acceptor By similarity
Binding site1721Substrate By similarity

Natural variations

Alternative sequence226 – 28055FHGNE…YSTRL → VRIGFMGMSLSGRTSRNIIS CRGLGSQRTVQESCPSCALQ MPATSTGRTLRWQATPLGSE RSGGGCVAVVPGPGA in isoform 2.
VSP_038179
Natural variant2721A → V in a colorectal cancer sample; somatic mutation. Ref.12
VAR_035846

Experimental info

Sequence conflict141H → R in BAD96577. Ref.3
Sequence conflict801L → V AA sequence Ref.7
Sequence conflict851L → G AA sequence Ref.7
Sequence conflict1511L → P in BAD96577. Ref.3
Sequence conflict1731I → V in BAD96577. Ref.3
Sequence conflict1861N → S in BAD96577. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 24, 2013. Version 4.
Checksum: FE76ED9CB28AB95C

FASTA28029,927
        10         20         30         40         50         60 
MLSAVARGYQ GWFHPCARLS VRMSSTGIDR KGVLANRVAV VTGSTSGIGF AIARRLARDG 

        70         80         90        100        110        120 
AHVVISSRKQ QNVDRAMAKL QGEGLSVAGI VCHVGKAEDR EQLVAKALEH CGGVDFLVCS 

       130        140        150        160        170        180 
AGVNPLVGST LGTSEQIWDK ILSVNVKSPA LLLSQLLPYM ENRRGAVILV SSIAAYNPVV 

       190        200        210        220        230        240 
ALGVYNVSKT ALLGLTRTLA LELAPKDIRV NCVVPGIIKT DFSKVFHGNE SLWKNFKEHH 

       250        260        270        280 
QLQRIGESED CAGIVSFLCS PDASYVNGEN IAVAGYSTRL 

« Hide

Isoform 2 [UniParc].

Checksum: AB4EB9C783A81710
Show »

FASTA30031,496

References

« Hide 'large scale' references
[1]"A nuclear protein, synthesized in growth-arrested human hepatoblastoma cells, is a novel member of the short-chain alcohol dehydrogenase family."
Gabrielli F., Donadel G., Bensi G., Heguy A., Melli M.
Eur. J. Biochem. 232:473-477(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 24-41.
Tissue: Hepatoma.
[2]"A human short-chain dehydrogenase/reductase gene: structure, chromosomal localization, tissue expression and subcellular localization of its product."
Pellegrini S., Censini S., Guidotti S., Iacopetti P., Rocchi M., Bianchi M., Covacci A., Gabrielli F.
Biochim. Biophys. Acta 1574:215-222(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION.
[3]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Liver.
[4]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-280 (ISOFORM 1).
Tissue: Skin.
[7]"Identification of a novel nuclear protein synthesized in growth-arrested human hepatoblastoma HepG2 cells."
Donadel G., Garzelli C., Frank R., Gabrielli F.
Eur. J. Biochem. 195:723-729(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 80-88; 141-146; 148-162 AND 198-205, SUBCELLULAR LOCATION.
[8]"Genomic organization of the human gene HEP27: alternative promoter usage in HepG2 cells and monocyte-derived dendritic cells."
Heinz S., Krause S.W., Gabrielli F., Wagner H.M., Andreesen R., Rehli M.
Genomics 79:608-615(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[9]"Hep27, a member of the short-chain dehydrogenase/reductase family, is an NADPH-dependent dicarbonyl reductase expressed in vascular endothelial tissue."
Shafqat N., Shafqat J., Eissner G., Marschall H.U., Tryggvason K., Eriksson U., Gabrielli F., Lardy H., Jornvall H., Oppermann U.
Cell. Mol. Life Sci. 63:1205-1213(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[10]"Mitochondrial Hep27 is a c-Myb target gene that inhibits Mdm2 and stabilizes p53."
Deisenroth C., Thorner A.R., Enomoto T., Perou C.M., Zhang Y.
Mol. Cell. Biol. 30:3981-3993(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MDM2, IDENTIFICATION OF MITOCHONDRIAL TRANSIT PEPTIDE CLEAVAGE SITE, SUBCELLULAR LOCATION.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-272.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U31875 mRNA. Translation: AAA82048.1.
AF244132 Genomic DNA. Translation: AAG33703.1.
AK222857 mRNA. Translation: BAD96577.1.
AL135999 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW66130.1.
CH471078 Genomic DNA. Translation: EAW66131.1.
BC002786 mRNA. Translation: AAH02786.1.
BC007339 mRNA. Translation: AAH07339.2.
PIRS66665.
RefSeqNP_005785.1. NM_005794.3.
NP_878912.1. NM_182908.4.
XP_005267306.1. XM_005267249.1.
UniGeneHs.272499.

3D structure databases

ProteinModelPortalQ13268.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115497. 7 interactions.
IntActQ13268. 13 interactions.
STRING9606.ENSP00000344674.

PTM databases

PhosphoSiteQ13268.

Polymorphism databases

DMDM527504085.

Proteomic databases

PaxDbQ13268.
PRIDEQ13268.

Protocols and materials databases

DNASU10202.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000250383; ENSP00000250383; ENSG00000100867. [Q13268-1]
ENST00000344777; ENSP00000344674; ENSG00000100867. [Q13268-2]
GeneID10202.
KEGGhsa:10202.
UCSCuc001wkt.4. human. [Q13268-2]
uc001wku.4. human.

Organism-specific databases

CTD10202.
GeneCardsGC14P024099.
HGNCHGNC:18349. DHRS2.
MIM615194. gene.
neXtProtNX_Q13268.
PharmGKBPA38318.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1028.
HOVERGENHBG105779.
KOK11164.
TreeFamTF315405.

Enzyme and pathway databases

SABIO-RKQ13268.

Gene expression databases

ArrayExpressQ13268.
BgeeQ13268.
CleanExHS_DHRS2.
GenevestigatorQ13268.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]
PRINTSPR00081. GDHRDH.
PR00080. SDRFAMILY.
PROSITEPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDHRS2. human.
GeneWikiDHRS2.
GenomeRNAi10202.
NextBio38614.
PROQ13268.
SOURCESearch...

Entry information

Entry nameDHRS2_HUMAN
AccessionPrimary (citable) accession number: Q13268
Secondary accession number(s): D3DS54 expand/collapse secondary AC list , Q53GS4, Q7Z789, Q9H2R2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 24, 2013
Last modified: April 16, 2014
This is version 126 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM