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Protein

Dehydrogenase/reductase SDR family member 2, mitochondrial

Gene

DHRS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionOxidoreductase

Enzyme and pathway databases

SABIO-RKiQ13268

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

EuPathDBiHostDB:ENSG00000100867.14
HGNCiHGNC:18349 DHRS2
MIMi615194 gene
neXtProtiNX_Q13268

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi59268
59269 [Q13268-2]

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, 31 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
GeneTreeiENSGT00920000148965
HOVERGENiHBG105779
InParanoidiQ13268
KOiK11164
OMAiHGNVIFT
OrthoDBiEOG091G0G3R
TreeFamiTF315405

Family and domain databases

InterProiView protein in InterPro
IPR027052 DHRS2
IPR036291 NAD(P)-bd_dom_sf
IPR020904 Sc_DH/Rdtase_CS
IPR002347 SDR_fam
PANTHERiPTHR43943:SF3 PTHR43943:SF3, 1 hit
PRINTSiPR00081 GDHRDH
PR00080 SDRFAMILY
SUPFAMiSSF51735 SSF51735, 1 hit
PROSITEiView protein in PROSITE
PS00061 ADH_SHORT, 1 hit

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 dbSNP:rs148991912Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiDHRS2_HUMAN
AccessioniPrimary (citable) accession number: Q13268
Secondary accession number(s): D3DS54
, Q53GS4, Q7Z789, Q9H2R2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 24, 2013
Last modified: July 18, 2018
This is version 166 of the entry and version 4 of the sequence. See 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

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