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Protein

Dehydrogenase/reductase SDR family member 2, mitochondrial

Gene

DHRS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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/p21.2 Publications

Kineticsi

  1. KM=0.3 mM for 1-Phenyl-1,2-propanedione1 Publication
  2. KM=1.1 mM for 2,3-Heptanedione1 Publication
  3. KM=0.8 mM for 3,4-Hexanedione1 Publication
  1. Vmax=0.52 mmol/min/mg enzyme with 1-Phenyl-1,2-propanedione as substrate1 Publication
  2. Vmax=0.64 mmol/min/mg enzyme with 2,3-Heptanedione as substrate1 Publication
  3. Vmax=0.35 mmol/min/mg enzyme with 3,4-Hexanedione as substrate1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei172 – 1721SubstrateBy similarity
Active sitei185 – 1851Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi40 – 6425NAD or NADPBy similarityAdd
BLAST

GO - Molecular functioni

  • carbonyl reductase (NADPH) activity Source: UniProtKB

GO - Biological processi

  • C21-steroid hormone metabolic process Source: UniProtKB
  • cellular response to oxidative stress Source: UniProtKB
  • myeloid dendritic cell differentiation Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • response to toxic substance Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Enzyme and pathway databases

SABIO-RKQ13268.

Names & Taxonomyi

Protein namesi
Recommended name:
Dehydrogenase/reductase SDR family member 2, mitochondrial (EC:1.1.1.-)
Alternative name(s):
Dicarbonyl reductase HEP27
Protein D
Short chain dehydrogenase/reductase family 25C member 1
Gene namesi
Name:DHRS2
Synonyms:SDR25C1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:18349. DHRS2.

Subcellular locationi

  • Mitochondrion matrix
  • Nucleus

  • Note: A minor fraction of the protein is translocated from the mitochondria to the nucleus, after cleavage of the targeting signal.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • mitochondrial matrix Source: UniProtKB-SubCell
  • mitochondrion Source: UniProtKB
  • nuclear envelope Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38318.

Polymorphism and mutation databases

BioMutaiDHRS2.
DMDMi527504085.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2323Mitochondrion1 PublicationAdd
BLAST
Chaini24 – 280257Dehydrogenase/reductase SDR family member 2, mitochondrialPRO_0000054642Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei96 – 961N6-acetyllysine; alternateBy similarity
Modified residuei96 – 961N6-succinyllysine; alternateBy similarity
Modified residuei219 – 2191N6-acetyllysine; alternateBy similarity
Modified residuei219 – 2191N6-succinyllysine; alternateBy similarity
Modified residuei237 – 2371N6-succinyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ13268.
PaxDbiQ13268.
PRIDEiQ13268.

PTM databases

PhosphoSiteiQ13268.

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

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.1 Publication

Gene expression databases

BgeeiQ13268.
CleanExiHS_DHRS2.
ExpressionAtlasiQ13268. baseline and differential.
GenevisibleiQ13268. HS.

Interactioni

Subunit structurei

Directly interacts with MDM2; this interaction occurs in the nucleus and does not target DHRS2 to degradation.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
APPBP2Q926243EBI-354324,EBI-743771

Protein-protein interaction databases

BioGridi115497. 14 interactions.
IntActiQ13268. 14 interactions.
STRINGi9606.ENSP00000344674.

Structurei

3D structure databases

ProteinModelPortaliQ13268.
SMRiQ13268. Positions 34-275.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG1028.
GeneTreeiENSGT00760000118868.
HOVERGENiHBG105779.
InParanoidiQ13268.
KOiK11164.
OMAiYFPRMEL.
TreeFamiTF315405.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR002198. DH_sc/Rdtase_SDR.
IPR027052. DHRS2.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]
PANTHERiPTHR24322:SF322. PTHR24322:SF322. 1 hit.
PRINTSiPR00081. GDHRDH.
PR00080. SDRFAMILY.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13268-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MLSAVARGYQ GWFHPCARLS VRMSSTGIDR KGVLANRVAV VTGSTSGIGF
60 70 80 90 100
AIARRLARDG AHVVISSRKQ QNVDRAMAKL QGEGLSVAGI VCHVGKAEDR
110 120 130 140 150
EQLVAKALEH CGGVDFLVCS AGVNPLVGST LGTSEQIWDK ILSVNVKSPA
160 170 180 190 200
LLLSQLLPYM ENRRGAVILV SSIAAYNPVV ALGVYNVSKT ALLGLTRTLA
210 220 230 240 250
LELAPKDIRV NCVVPGIIKT DFSKVFHGNE SLWKNFKEHH QLQRIGESED
260 270 280
CAGIVSFLCS PDASYVNGEN IAVAGYSTRL
Length:280
Mass (Da):29,927
Last modified:July 24, 2013 - v4
Checksum:iFE76ED9CB28AB95C
GO
Isoform 2 (identifier: Q13268-2) [UniParc]FASTAAdd to basket

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

Show »
Length:300
Mass (Da):31,496
Checksum:iAB4EB9C783A81710
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti14 – 141H → R in BAD96577 (Ref. 3) Curated
Sequence conflicti80 – 801L → V AA sequence (PubMed:1847869).Curated
Sequence conflicti85 – 851L → G AA sequence (PubMed:1847869).Curated
Sequence conflicti151 – 1511L → P in BAD96577 (Ref. 3) Curated
Sequence conflicti173 – 1731I → V in BAD96577 (Ref. 3) Curated
Sequence conflicti186 – 1861N → S in BAD96577 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti272 – 2721A → V in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_035846

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei226 – 28055FHGNE…YSTRL → VRIGFMGMSLSGRTSRNIIS CRGLGSQRTVQESCPSCALQ MPATSTGRTLRWQATPLGSE RSGGGCVAVVPGPGA in isoform 2. 1 PublicationVSP_038179Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41927.1. [Q13268-2]
CCDS9604.1. [Q13268-1]
PIRiS66665.
RefSeqiNP_005785.1. NM_005794.3. [Q13268-1]
NP_878912.1. NM_182908.4. [Q13268-2]
XP_005267306.1. XM_005267249.1. [Q13268-1]
XP_006720063.1. XM_006720000.2. [Q13268-1]
XP_006720064.1. XM_006720001.2. [Q13268-1]
UniGeneiHs.272499.

Genome annotation databases

EnsembliENST00000250383; ENSP00000250383; ENSG00000100867.
ENST00000344777; ENSP00000344674; ENSG00000100867. [Q13268-2]
ENST00000611765; ENSP00000481607; ENSG00000100867. [Q13268-2]
GeneIDi10202.
KEGGihsa:10202.
UCSCiuc001wkt.4. human. [Q13268-2]
uc001wku.4. human.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41927.1. [Q13268-2]
CCDS9604.1. [Q13268-1]
PIRiS66665.
RefSeqiNP_005785.1. NM_005794.3. [Q13268-1]
NP_878912.1. NM_182908.4. [Q13268-2]
XP_005267306.1. XM_005267249.1. [Q13268-1]
XP_006720063.1. XM_006720000.2. [Q13268-1]
XP_006720064.1. XM_006720001.2. [Q13268-1]
UniGeneiHs.272499.

3D structure databases

ProteinModelPortaliQ13268.
SMRiQ13268. Positions 34-275.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115497. 14 interactions.
IntActiQ13268. 14 interactions.
STRINGi9606.ENSP00000344674.

PTM databases

PhosphoSiteiQ13268.

Polymorphism and mutation databases

BioMutaiDHRS2.
DMDMi527504085.

Proteomic databases

MaxQBiQ13268.
PaxDbiQ13268.
PRIDEiQ13268.

Protocols and materials databases

DNASUi10202.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250383; ENSP00000250383; ENSG00000100867.
ENST00000344777; ENSP00000344674; ENSG00000100867. [Q13268-2]
ENST00000611765; ENSP00000481607; ENSG00000100867. [Q13268-2]
GeneIDi10202.
KEGGihsa:10202.
UCSCiuc001wkt.4. human. [Q13268-2]
uc001wku.4. human.

Organism-specific databases

CTDi10202.
GeneCardsiGC14P024099.
HGNCiHGNC:18349. DHRS2.
MIMi615194. gene.
neXtProtiNX_Q13268.
PharmGKBiPA38318.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1028.
GeneTreeiENSGT00760000118868.
HOVERGENiHBG105779.
InParanoidiQ13268.
KOiK11164.
OMAiYFPRMEL.
TreeFamiTF315405.

Enzyme and pathway databases

SABIO-RKQ13268.

Miscellaneous databases

ChiTaRSiDHRS2. human.
GeneWikiiDHRS2.
GenomeRNAii10202.
NextBioi38614.
PROiQ13268.
SOURCEiSearch...

Gene expression databases

BgeeiQ13268.
CleanExiHS_DHRS2.
ExpressionAtlasiQ13268. baseline and differential.
GenevisibleiQ13268. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR002198. DH_sc/Rdtase_SDR.
IPR027052. DHRS2.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]
PANTHERiPTHR24322:SF322. PTHR24322:SF322. 1 hit.
PRINTSiPR00081. GDHRDH.
PR00080. SDRFAMILY.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-272.

Entry informationi

Entry nameiDHRS2_HUMAN
AccessioniPrimary (citable) accession number: Q13268
Secondary accession number(s): D3DS54
, Q53GS4, Q7Z789, Q9H2R2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 24, 2013
Last modified: July 22, 2015
This is version 140 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.