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Protein

Hydroxyproline dehydrogenase

Gene

PRODH2

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

Functioni

Dehydrogenase that converts trans-4-L-hydroxyproline to delta-1-pyrroline-3-hydroxy-5-carboxylate (Hyp) using ubiquinone-10 as the terminal electron acceptor. Can also use proline as a substrate but with a very much lower efficiency. Does not react with other diastereomers of Hyp: trans-4-D-hydroxyproline and cis-4-L-hydroxyproline. Ubiquininone analogs such as menadione, duroquinone and ubiquinone-1 react more efficiently than oxygen as the terminal electron acceptor during catalysis.1 Publication

Catalytic activityi

trans-4-hydroxy-L-proline + ubiquinone-10 = (3R,5S)-1-pyrroline-3-hydroxy-5-carboxylate + ubiquinol-10.1 Publication
L-proline + a quinone = (S)-1-pyrroline-5-carboxylate + a quinol.1 Publication

Cofactori

FAD1 Publication

Enzyme regulationi

Hydroproxyproline dehydrogenase activity is inhibited by THFA,(1R,3R)3-OH-cyclopentane-COOH and 5-OH-1H-pyrazole-3-COOH.1 Publication

Kineticsi

kcat with trans-4-L-hydroxyproline (Hyp) and ubiquinone-1 is 0.19 sec(-1). Proline is unable to saturate PRODH2 at least up to 750mM. kcat/KM with proline and ubiquinone-10: 0.075 M(-1)/sec. kcat with oxygen, duroquinone, menadione and CoQ1 and with trans-4-L-hydroxyproline are 0.002 sec(-1), 0.27 sec(-1), 0.28 sec(-1) and 0.19 sec(-1), respectively.1 Publication
  1. KM=200 mM for trans-4-L-hydroxyproline1 Publication
  2. KM=28 mM for oxygen1 Publication
  3. KM=143 µM for duroquinone1 Publication
  4. KM=25 µM for menadione1 Publication
  5. KM=124 µM for ubiquinone-11 Publication

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionOxidoreductase
    Biological processProline metabolism
    LigandFAD, Flavoprotein

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER66-34410.
    ReactomeiR-HSA-389661. Glyoxylate metabolism and glycine degradation.
    R-HSA-70688. Proline catabolism.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hydroxyproline dehydrogenase1 Publication (EC:1.5.5.-1 Publication)
    Short name:
    HYPDH1 Publication
    Alternative name(s):
    Kidney and liver proline oxidase 1
    Short name:
    HsPOX1
    Probable proline dehydrogenase 2Imported (EC:1.5.5.21 Publication)
    Probable proline oxidase 2
    Gene namesi
    Name:PRODH2Imported
    Synonyms:HSPOX1Imported, HYPDH1 Publication
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000250799.9.
    HGNCiHGNC:17325. PRODH2.

    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

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi58510.
    MalaCardsiPRODH2.
    OpenTargetsiENSG00000250799.
    PharmGKBiPA33802.

    Polymorphism and mutation databases

    BioMutaiPRODH2.
    DMDMi74720632.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003086231 – 536Hydroxyproline dehydrogenaseAdd BLAST536

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei386N6-acetyllysineBy similarity1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ9UF12.
    PaxDbiQ9UF12.
    PeptideAtlasiQ9UF12.
    PRIDEiQ9UF12.

    PTM databases

    iPTMnetiQ9UF12.

    Expressioni

    Gene expression databases

    BgeeiENSG00000250799.
    CleanExiHS_PRODH2.
    ExpressionAtlasiQ9UF12. baseline and differential.
    GenevisibleiQ9UF12. HS.

    Organism-specific databases

    HPAiHPA051287.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000301175.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UF12.
    SMRiQ9UF12.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the proline oxidase family.Curated

    Phylogenomic databases

    eggNOGiKOG0186. Eukaryota.
    COG0506. LUCA.
    GeneTreeiENSGT00390000006265.
    HOGENOMiHOG000233406.
    HOVERGENiHBG108294.
    InParanoidiQ9UF12.
    KOiK11394.
    OMAiIDAEESW.
    OrthoDBiEOG091G09N3.
    PhylomeDBiQ9UF12.
    TreeFamiTF313544.

    Family and domain databases

    Gene3Di3.20.20.220. 1 hit.
    InterProiView protein in InterPro
    IPR029041. FAD-linked_oxidoreductase-like.
    IPR002872. Proline_DH_dom.
    IPR015659. Proline_oxidase.
    PANTHERiPTHR13914. PTHR13914. 1 hit.
    PfamiView protein in Pfam
    PF01619. Pro_dh. 1 hit.
    SUPFAMiSSF51730. SSF51730. 2 hits.

    Sequencei

    Sequence statusi: Complete.

    Q9UF12-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSPRVVSNSS VLASQSVGIT NVRTVFSNVF NNTTAFPILR GSNCHKITAP
    60 70 80 90 100
    GLGKGQLVNL LPPENLPWCG GSQGPRMLRT CYVLCSQAGP PSRGWQSLSF
    110 120 130 140 150
    DGGAFHLKGT GELTRALLVL RLCAWPPLVT HGLLLQAWSR RLLGSRLSGA
    160 170 180 190 200
    FLRASVYGQF VAGETAEEVK GCVQQLRTLS LRPLLAVPTE EEPDSAAKSG
    210 220 230 240 250
    EAWYEGNLGA MLRCVDLSRG LLEPPSLAEA SLMQLKVTAL TSTRLCKELA
    260 270 280 290 300
    SWVRRPGASL ELSPERLAEA MDSGQNLQVS CLNAEQNQHL RASLSRLHRV
    310 320 330 340 350
    AQYARAQHVR LLVDAEYTSL NPALSLLVAA LAVRWNSPGE GGPWVWNTYQ
    360 370 380 390 400
    ACLKDTFERL GRDAEAAHRA GLAFGVKLVR GAYLDKERAV AQLHGMEDPT
    410 420 430 440 450
    QPDYEATSQS YSRCLELMLT HVARHGPMCH LMVASHNEES VRQATKRMWE
    460 470 480 490 500
    LGIPLDGTVC FGQLLGMCDH VSLALGQAGY VVYKSIPYGS LEEVIPYLIR
    510 520 530
    RAQENRSVLQ GARREQELLS QELWRRLLPG CRRIPH
    Length:536
    Mass (Da):58,871
    Last modified:May 1, 2000 - v1
    Checksum:i81EB2F4B21E39E09
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_03685291P → R. Corresponds to variant dbSNP:rs3848666Ensembl.1
    Natural variantiVAR_036853525R → Q. Corresponds to variant dbSNP:rs3761097Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U80018 mRNA. Translation: AAF21465.1.
    CCDSiCCDS12478.1.
    RefSeqiNP_067055.1. NM_021232.1.
    UniGeneiHs.515366.

    Genome annotation databases

    EnsembliENST00000301175; ENSP00000301175; ENSG00000250799.
    GeneIDi58510.
    KEGGihsa:58510.
    UCSCiuc002obx.1. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiHYPDH_HUMAN
    AccessioniPrimary (citable) accession number: Q9UF12
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 23, 2007
    Last sequence update: May 1, 2000
    Last modified: September 27, 2017
    This is version 111 of the entry and version 1 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, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: 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