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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)DescriptionActionsGraphical viewLength
Binding sitei172SubstrateBy similarity1
Active sitei185Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi40 – 64NAD or NADPBy similarityAdd BLAST25

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

BioCyciZFISH:ENSG00000100867-MONOMER.
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
Proteomesi
  • UP000005640 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

DisGeNETi10202.
OpenTargetsiENSG00000100867.
PharmGKBiPA38318.

Polymorphism and mutation databases

BioMutaiDHRS2.
DMDMi527504085.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 23Mitochondrion1 PublicationAdd BLAST23
ChainiPRO_000005464224 – 280Dehydrogenase/reductase SDR family member 2, mitochondrialAdd BLAST257

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei96N6-acetyllysine; alternateBy similarity1
Modified residuei96N6-succinyllysine; alternateBy similarity1
Modified residuei219N6-acetyllysine; alternateBy similarity1
Modified residuei219N6-succinyllysine; alternateBy similarity1
Modified residuei223PhosphoserineBy similarity1
Modified residuei237N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ13268.
MaxQBiQ13268.
PaxDbiQ13268.
PeptideAtlasiQ13268.
PRIDEiQ13268.

PTM databases

iPTMnetiQ13268.
PhosphoSitePlusiQ13268.

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

BgeeiENSG00000100867.
CleanExiHS_DHRS2.
ExpressionAtlasiQ13268. baseline and differential.
GenevisibleiQ13268. HS.

Organism-specific databases

HPAiHPA053915.
HPA069551.

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. 26 interactors.
IntActiQ13268. 19 interactors.
STRINGi9606.ENSP00000344674.

Structurei

3D structure databases

ProteinModelPortaliQ13268.
SMRiQ13268.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0725. Eukaryota.
COG1028. LUCA.
GeneTreeiENSGT00760000118868.
HOVERGENiHBG105779.
InParanoidiQ13268.
KOiK11164.
OMAiQEGCNIA.
OrthoDBiEOG091G0G3R.
TreeFamiTF315405.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR027052. DHRS2.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 2 hits.
PTHR24322:SF322. PTHR24322:SF322. 2 hits.
PRINTSiPR00081. GDHRDH.
PR00080. SDRFAMILY.
SUPFAMiSSF51735. SSF51735. 1 hit.
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)DescriptionActionsGraphical viewLength
Sequence conflicti14H → R in BAD96577 (Ref. 3) Curated1
Sequence conflicti80L → V AA sequence (PubMed:1847869).Curated1
Sequence conflicti85L → G AA sequence (PubMed:1847869).Curated1
Sequence conflicti151L → P in BAD96577 (Ref. 3) Curated1
Sequence conflicti173I → V in BAD96577 (Ref. 3) Curated1
Sequence conflicti186N → S in BAD96577 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035846272A → V in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs148991912dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038179226 – 280FHGNE…YSTRL → VRIGFMGMSLSGRTSRNIIS CRGLGSQRTVQESCPSCALQ MPATSTGRTLRWQATPLGSE RSGGGCVAVVPGPGA in isoform 2. 1 PublicationAdd BLAST55

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_006720064.1. XM_006720001.3. [Q13268-1]
UniGeneiHs.272499.

Genome annotation databases

EnsembliENST00000250383; ENSP00000250383; ENSG00000100867. [Q13268-1]
ENST00000344777; ENSP00000344674; ENSG00000100867. [Q13268-2]
ENST00000611765; ENSP00000481607; ENSG00000100867. [Q13268-2]
GeneIDi10202.
KEGGihsa:10202.
UCSCiuc001wkt.5. human. [Q13268-1]

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_006720064.1. XM_006720001.3. [Q13268-1]
UniGeneiHs.272499.

3D structure databases

ProteinModelPortaliQ13268.
SMRiQ13268.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115497. 26 interactors.
IntActiQ13268. 19 interactors.
STRINGi9606.ENSP00000344674.

PTM databases

iPTMnetiQ13268.
PhosphoSitePlusiQ13268.

Polymorphism and mutation databases

BioMutaiDHRS2.
DMDMi527504085.

Proteomic databases

EPDiQ13268.
MaxQBiQ13268.
PaxDbiQ13268.
PeptideAtlasiQ13268.
PRIDEiQ13268.

Protocols and materials databases

DNASUi10202.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250383; ENSP00000250383; ENSG00000100867. [Q13268-1]
ENST00000344777; ENSP00000344674; ENSG00000100867. [Q13268-2]
ENST00000611765; ENSP00000481607; ENSG00000100867. [Q13268-2]
GeneIDi10202.
KEGGihsa:10202.
UCSCiuc001wkt.5. human. [Q13268-1]

Organism-specific databases

CTDi10202.
DisGeNETi10202.
GeneCardsiDHRS2.
HGNCiHGNC:18349. DHRS2.
HPAiHPA053915.
HPA069551.
MIMi615194. gene.
neXtProtiNX_Q13268.
OpenTargetsiENSG00000100867.
PharmGKBiPA38318.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0725. Eukaryota.
COG1028. LUCA.
GeneTreeiENSGT00760000118868.
HOVERGENiHBG105779.
InParanoidiQ13268.
KOiK11164.
OMAiQEGCNIA.
OrthoDBiEOG091G0G3R.
TreeFamiTF315405.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100867-MONOMER.
SABIO-RKQ13268.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000100867.
CleanExiHS_DHRS2.
ExpressionAtlasiQ13268. baseline and differential.
GenevisibleiQ13268. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR027052. DHRS2.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 2 hits.
PTHR24322:SF322. PTHR24322:SF322. 2 hits.
PRINTSiPR00081. GDHRDH.
PR00080. SDRFAMILY.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 153 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

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 one 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.