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Q13268

- DHRS2_HUMAN

UniProt

Q13268 - DHRS2_HUMAN

Protein

Dehydrogenase/reductase SDR family member 2, mitochondrial

Gene

DHRS2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 4 (24 Jul 2013)
      Previous versions | rss
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    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

    Vmax=0.52 mmol/min/mg enzyme with 1-Phenyl-1,2-propanedione as substrate1 Publication

    Vmax=0.64 mmol/min/mg enzyme with 2,3-Heptanedione as substrate1 Publication

    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

    1. carbonyl reductase (NADPH) activity Source: UniProtKB

    GO - Biological processi

    1. C21-steroid hormone metabolic process Source: UniProtKB
    2. cellular response to oxidative stress Source: UniProtKB
    3. myeloid dendritic cell differentiation Source: UniProtKB
    4. negative regulation of apoptotic process Source: UniProtKB
    5. negative regulation of cell proliferation Source: UniProtKB
    6. oxidation-reduction process Source: UniProtKB
    7. response to toxic substance Source: UniProtKB

    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
    Gene namesi
    Name:DHRS2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: 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

    1. cytoplasm Source: UniProtKB
    2. extracellular vesicular exosome Source: UniProt
    3. mitochondrial matrix Source: UniProtKB-SubCell
    4. mitochondrion Source: UniProtKB
    5. nuclear envelope Source: UniProtKB
    6. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Mitochondrion, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA38318.

    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

    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

    ArrayExpressiQ13268.
    BgeeiQ13268.
    CleanExiHS_DHRS2.
    GenevestigatoriQ13268.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    BioGridi115497. 9 interactions.
    IntActiQ13268. 13 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.
    HOVERGENiHBG105779.
    KOiK11164.
    OMAiGPMRTIR.
    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. Align

    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

    MLSAVARGYQ GWFHPCARLS VRMSSTGIDR KGVLANRVAV VTGSTSGIGF    50
    AIARRLARDG AHVVISSRKQ QNVDRAMAKL QGEGLSVAGI VCHVGKAEDR 100
    EQLVAKALEH CGGVDFLVCS AGVNPLVGST LGTSEQIWDK ILSVNVKSPA 150
    LLLSQLLPYM ENRRGAVILV SSIAAYNPVV ALGVYNVSKT ALLGLTRTLA 200
    LELAPKDIRV NCVVPGIIKT DFSKVFHGNE SLWKNFKEHH QLQRIGESED 250
    CAGIVSFLCS PDASYVNGEN IAVAGYSTRL 280
    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. 1 PublicationCurated
    Sequence conflicti80 – 801L → V AA sequence (PubMed:1847869)Curated
    Sequence conflicti85 – 851L → G AA sequence (PubMed:1847869)Curated
    Sequence conflicti151 – 1511L → P in BAD96577. 1 PublicationCurated
    Sequence conflicti173 – 1731I → V in BAD96577. 1 PublicationCurated
    Sequence conflicti186 – 1861N → S in BAD96577. 1 PublicationCurated

    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:
    EMBL
    GenBank
    DDBJ
    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_006720000.1. [Q13268-1]
    XP_006720064.1. XM_006720001.1. [Q13268-1]
    UniGeneiHs.272499.

    Genome annotation databases

    EnsembliENST00000250383; ENSP00000250383; ENSG00000100867. [Q13268-1]
    ENST00000344777; ENSP00000344674; ENSG00000100867. [Q13268-2]
    GeneIDi10202.
    KEGGihsa:10202.
    UCSCiuc001wkt.4. human. [Q13268-2]
    uc001wku.4. human.

    Polymorphism databases

    DMDMi527504085.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS41927.1. [Q13268-2 ]
    CCDS9604.1. [Q13268-1 ]
    PIRi S66665.
    RefSeqi NP_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_006720000.1. [Q13268-1 ]
    XP_006720064.1. XM_006720001.1. [Q13268-1 ]
    UniGenei Hs.272499.

    3D structure databases

    ProteinModelPortali Q13268.
    SMRi Q13268. Positions 34-275.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115497. 9 interactions.
    IntActi Q13268. 13 interactions.
    STRINGi 9606.ENSP00000344674.

    PTM databases

    PhosphoSitei Q13268.

    Polymorphism databases

    DMDMi 527504085.

    Proteomic databases

    MaxQBi Q13268.
    PaxDbi Q13268.
    PRIDEi Q13268.

    Protocols and materials databases

    DNASUi 10202.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000250383 ; ENSP00000250383 ; ENSG00000100867 . [Q13268-1 ]
    ENST00000344777 ; ENSP00000344674 ; ENSG00000100867 . [Q13268-2 ]
    GeneIDi 10202.
    KEGGi hsa:10202.
    UCSCi uc001wkt.4. human. [Q13268-2 ]
    uc001wku.4. human.

    Organism-specific databases

    CTDi 10202.
    GeneCardsi GC14P024099.
    HGNCi HGNC:18349. DHRS2.
    MIMi 615194. gene.
    neXtProti NX_Q13268.
    PharmGKBi PA38318.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1028.
    HOVERGENi HBG105779.
    KOi K11164.
    OMAi GPMRTIR.
    TreeFami TF315405.

    Enzyme and pathway databases

    SABIO-RK Q13268.

    Miscellaneous databases

    ChiTaRSi DHRS2. human.
    GeneWikii DHRS2.
    GenomeRNAii 10202.
    NextBioi 38614.
    PROi Q13268.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q13268.
    Bgeei Q13268.
    CleanExi HS_DHRS2.
    Genevestigatori Q13268.

    Family and domain databases

    Gene3Di 3.40.50.720. 1 hit.
    InterProi IPR002198. DH_sc/Rdtase_SDR.
    IPR027052. DHRS2.
    IPR002347. Glc/ribitol_DH.
    IPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    [Graphical view ]
    PANTHERi PTHR24322:SF322. PTHR24322:SF322. 1 hit.
    PRINTSi PR00081. GDHRDH.
    PR00080. SDRFAMILY.
    PROSITEi PS00061. ADH_SHORT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 131 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