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Protein

15-hydroxyprostaglandin dehydrogenase [NAD(+)]

Gene

HPGD

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

Functioni

Prostaglandin inactivation. Contributes to the regulation of events that are under the control of prostaglandin levels. Catalyzes the NAD-dependent dehydrogenation of lipoxin A4 to form 15-oxo-lipoxin A4. Inhibits in vivo proliferation of colon cancer cells.3 Publications

Catalytic activityi

(5Z,13E,15S)-11-alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+ = (5Z,13E)-11-alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH.

Kineticsi

  1. KM=3.4 µM for prostaglandin E21 Publication
  2. KM=38 µM for NAD1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei91NAD; via carbonyl oxygen1 Publication1
    Binding sitei138SubstrateCurated1
    Binding sitei148SubstrateCurated1
    Active sitei151Proton acceptor1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi12 – 20NAD1 Publication9
    Nucleotide bindingi36 – 37NAD1 Publication2
    Nucleotide bindingi63 – 65NAD1 Publication3
    Nucleotide bindingi151 – 155NAD1 Publication5
    Nucleotide bindingi186 – 188NAD1 Publication3

    GO - Molecular functioni

    • 15-hydroxyprostaglandin dehydrogenase (NAD+) activity Source: UniProtKB
    • catalytic activity Source: UniProtKB
    • NAD+ binding Source: UniProtKB
    • NAD binding Source: UniProtKB
    • prostaglandin E receptor activity Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionOxidoreductase
    Biological processFatty acid metabolism, Lipid metabolism, Prostaglandin metabolism
    LigandNAD

    Enzyme and pathway databases

    BRENDAi1.1.1.141 2681
    ReactomeiR-HSA-2142700 Synthesis of Lipoxins (LX)
    R-HSA-2162123 Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
    R-HSA-9018676 Biosynthesis of D-series resolvins
    R-HSA-9018896 Biosynthesis of E-series 18(S)-resolvins
    SABIO-RKiP15428
    SIGNORiP15428

    Chemistry databases

    SwissLipidsiSLP:000000732

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    15-hydroxyprostaglandin dehydrogenase [NAD(+)] (EC:1.1.1.141)
    Short name:
    15-PGDH
    Alternative name(s):
    Prostaglandin dehydrogenase 1
    Short chain dehydrogenase/reductase family 36C member 1
    Gene namesi
    Name:HPGD
    Synonyms:PGDH1, SDR36C1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 4

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000164120.13
    HGNCiHGNC:5154 HPGD
    MIMi601688 gene
    neXtProtiNX_P15428

    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

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (PHOAR1)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease.
    See also OMIM:259100
    Cranioosteoarthropathy (COA)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of osteoarthropathy characterized by swelling of the joints, digital clubbing, hyperhidrosis, delayed closure of the fontanels, periostosis, and variable patent ductus arteriosus. Pachydermia is not a prominent feature.
    See also OMIM:259100
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_046209140A → P in COA; inactive. 1 PublicationCorresponds to variant dbSNP:rs121434480EnsemblClinVar.1
    Isolated congenital nail clubbing (ICNC)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA rare genodermatosis characterized by enlargement of the nail plate and terminal segments of the fingers and toes, resulting from proliferation of the connective tissues between the nail matrix and the distal phalanx. It is usually symmetrical and bilateral (in some cases unilateral). In nail clubbing usually the distal end of the nail matrix is relatively high compared to the proximal end, while the nail plate is complete but its dimensions and diameter more or less vary in comparison to normal. There may be different fingers and toes involved to varying degrees. Some fingers or toes are spared, but the thumbs are almost always involved.
    See also OMIM:119900
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_060792193S → P in ICNC. 1 PublicationCorresponds to variant dbSNP:rs121434481EnsemblClinVar.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi148Q → A: Loss of activity. 1 Publication1
    Mutagenesisi148Q → E, H or N: Reduced affinity for NAD and prostaglandin E2. 1 Publication1
    Mutagenesisi151Y → A: Loss of activity. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Tumor suppressor

    Organism-specific databases

    DisGeNETi3248
    MalaCardsiHPGD
    MIMi119900 phenotype
    259100 phenotype
    OpenTargetsiENSG00000164120
    Orphaneti1525 Cranio-osteoarthropathy
    217059 Isolated congenital digital clubbing
    2796 Pachydermoperiostosis
    PharmGKBiPA29424

    Chemistry databases

    ChEMBLiCHEMBL1293255
    DrugBankiDB00157 NADH
    GuidetoPHARMACOLOGYi1384

    Polymorphism and mutation databases

    BioMutaiHPGD
    DMDMi129889

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000547441 – 26615-hydroxyprostaglandin dehydrogenase [NAD(+)]Add BLAST266

    Proteomic databases

    EPDiP15428
    MaxQBiP15428
    PaxDbiP15428
    PeptideAtlasiP15428
    PRIDEiP15428
    ProteomicsDBi53141
    53142 [P15428-2]

    2D gel databases

    SWISS-2DPAGEiP15428

    PTM databases

    iPTMnetiP15428
    PhosphoSitePlusiP15428

    Expressioni

    Tissue specificityi

    Detected in colon epithelium (at protein level).1 Publication

    Inductioni

    Down-regulated by cortisol, dexamethasone and betamethasone. Down-regulated in colon cancer. Up-regulated by TGFB1.2 Publications

    Gene expression databases

    BgeeiENSG00000164120
    CleanExiHS_HPGD
    ExpressionAtlasiP15428 baseline and differential
    GenevisibleiP15428 HS

    Organism-specific databases

    HPAiHPA004919
    HPA005679

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    GO - Molecular functioni

    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi109485, 1 interactor
    IntActiP15428, 1 interactor
    STRINGi9606.ENSP00000296522

    Chemistry databases

    BindingDBiP15428

    Structurei

    Secondary structure

    1266
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi7 – 11Combined sources5
    Turni12 – 14Combined sources3
    Helixi16 – 27Combined sources12
    Beta strandi31 – 37Combined sources7
    Helixi39 – 49Combined sources11
    Turni50 – 52Combined sources3
    Helixi55 – 57Combined sources3
    Beta strandi58 – 62Combined sources5
    Helixi68 – 82Combined sources15
    Beta strandi87 – 90Combined sources4
    Beta strandi97 – 99Combined sources3
    Helixi100 – 107Combined sources8
    Helixi109 – 122Combined sources14
    Helixi124 – 126Combined sources3
    Beta strandi131 – 136Combined sources6
    Helixi139 – 141Combined sources3
    Helixi149 – 172Combined sources24
    Beta strandi176 – 184Combined sources9
    Beta strandi186 – 188Combined sources3
    Helixi189 – 192Combined sources4
    Helixi193 – 195Combined sources3
    Helixi197 – 200Combined sources4
    Helixi201 – 206Combined sources6
    Helixi207 – 217Combined sources11
    Helixi222 – 234Combined sources13
    Beta strandi242 – 246Combined sources5
    Turni247 – 249Combined sources3
    Beta strandi250 – 253Combined sources4

    3D structure databases

    ProteinModelPortaliP15428
    SMRiP15428
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP15428

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG4169 Eukaryota
    COG1028 LUCA
    GeneTreeiENSGT00920000148965
    HOGENOMiHOG000070121
    HOVERGENiHBG107379
    InParanoidiP15428
    KOiK00069
    OMAiSCEVHYS
    OrthoDBiEOG091G0OC9
    PhylomeDBiP15428
    TreeFamiTF324093

    Family and domain databases

    InterProiView protein in InterPro
    IPR036291 NAD(P)-bd_dom_sf
    IPR020904 Sc_DH/Rdtase_CS
    IPR002347 SDR_fam
    PfamiView protein in Pfam
    PF00106 adh_short, 1 hit
    PRINTSiPR00081 GDHRDH
    PR00080 SDRFAMILY
    SUPFAMiSSF51735 SSF51735, 1 hit
    PROSITEiView protein in PROSITE
    PS00061 ADH_SHORT, 1 hit

    Sequences (5)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P15428-1) [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
    MHVNGKVALV TGAAQGIGRA FAEALLLKGA KVALVDWNLE AGVQCKAALD
    60 70 80 90 100
    EQFEPQKTLF IQCDVADQQQ LRDTFRKVVD HFGRLDILVN NAGVNNEKNW
    110 120 130 140 150
    EKTLQINLVS VISGTYLGLD YMSKQNGGEG GIIINMSSLA GLMPVAQQPV
    160 170 180 190 200
    YCASKHGIVG FTRSAALAAN LMNSGVRLNA ICPGFVNTAI LESIEKEENM
    210 220 230 240 250
    GQYIEYKDHI KDMIKYYGIL DPPLIANGLI TLIEDDALNG AIMKITTSKG
    260
    IHFQDYDTTP FQAKTQ
    Length:266
    Mass (Da):28,977
    Last modified:April 1, 1990 - v1
    Checksum:iB860D2DE80E49514
    GO
    Isoform 2 (identifier: P15428-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         167-266: LAANLMNSGV...DTTPFQAKTQ → PTIDCQWIDNTH

    Show »
    Length:178
    Mass (Da):19,284
    Checksum:i685B577B3CA27EE3
    GO
    Isoform 3 (identifier: P15428-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-121: Missing.

    Show »
    Length:145
    Mass (Da):15,696
    Checksum:i7113DD63B7540112
    GO
    Isoform 4 (identifier: P15428-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         140-143: AGLM → AAHH
         144-266: Missing.

    Show »
    Length:143
    Mass (Da):15,534
    Checksum:i67C9DD0CC7E3366C
    GO
    Isoform 5 (identifier: P15428-5) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         73-140: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:198
    Mass (Da):21,526
    Checksum:i1D571F22D8738F64
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti50D → H in AAA89175 (PubMed:1697582).Curated1
    Sequence conflicti50D → H in AAA89174 (PubMed:1697582).Curated1
    Sequence conflicti97E → K in CAA57843 (PubMed:7557451).Curated1
    Sequence conflicti219I → V in BAG61916 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_046209140A → P in COA; inactive. 1 PublicationCorresponds to variant dbSNP:rs121434480EnsemblClinVar.1
    Natural variantiVAR_060792193S → P in ICNC. 1 PublicationCorresponds to variant dbSNP:rs121434481EnsemblClinVar.1
    Natural variantiVAR_006972217Y → C. Corresponds to variant dbSNP:rs140209262Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0451061 – 121Missing in isoform 3. 1 PublicationAdd BLAST121
    Alternative sequenceiVSP_04557973 – 140Missing in isoform 5. 1 PublicationAdd BLAST68
    Alternative sequenceiVSP_045107140 – 143AGLM → AAHH in isoform 4. 1 Publication4
    Alternative sequenceiVSP_045108144 – 266Missing in isoform 4. 1 PublicationAdd BLAST123
    Alternative sequenceiVSP_043032167 – 266LAANL…QAKTQ → PTIDCQWIDNTH in isoform 2. 2 PublicationsAdd BLAST100

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L76465 mRNA Translation: AAA89175.1
    J05594 mRNA Translation: AAA89174.1
    X82460 mRNA Translation: CAA57843.1
    U63296 mRNA Translation: AAB53034.1
    AK296642 mRNA Translation: BAH12408.1
    AK300125 mRNA Translation: BAG61916.1
    AK300524 mRNA Translation: BAG62236.1
    AK300940 mRNA Translation: BAG62569.1
    AK314624 mRNA Translation: BAG37190.1
    DQ903072 Genomic DNA Translation: ABI75347.1
    AC096751 Genomic DNA No translation available.
    CH471056 Genomic DNA Translation: EAX04734.1
    CH471056 Genomic DNA Translation: EAX04735.1
    CH471056 Genomic DNA Translation: EAX04736.1
    CH471056 Genomic DNA Translation: EAX04737.1
    BC018986 mRNA Translation: AAH18986.1
    CCDSiCCDS3821.1 [P15428-1]
    CCDS54821.1 [P15428-2]
    CCDS58933.1 [P15428-3]
    CCDS58934.1 [P15428-5]
    CCDS58935.1 [P15428-4]
    PIRiA35802
    RefSeqiNP_000851.2, NM_000860.5 [P15428-1]
    NP_001139288.1, NM_001145816.2 [P15428-2]
    NP_001243230.1, NM_001256301.1 [P15428-3]
    NP_001243234.1, NM_001256305.1 [P15428-4]
    NP_001243235.1, NM_001256306.1 [P15428-5]
    NP_001243236.1, NM_001256307.1 [P15428-3]
    UniGeneiHs.596913

    Genome annotation databases

    EnsembliENST00000296521; ENSP00000296521; ENSG00000164120 [P15428-2]
    ENST00000296522; ENSP00000296522; ENSG00000164120 [P15428-1]
    ENST00000422112; ENSP00000398720; ENSG00000164120 [P15428-5]
    ENST00000510901; ENSP00000422418; ENSG00000164120 [P15428-3]
    ENST00000541923; ENSP00000438017; ENSG00000164120 [P15428-3]
    ENST00000542498; ENSP00000443644; ENSG00000164120 [P15428-4]
    GeneIDi3248
    KEGGihsa:3248
    UCSCiuc003itu.3 human [P15428-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiPGDH_HUMAN
    AccessioniPrimary (citable) accession number: P15428
    Secondary accession number(s): B4DTA4
    , B4DU74, B4DV57, D3DP43, E7EV11, O00749, Q06F08, Q12998
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: April 1, 1990
    Last modified: July 18, 2018
    This is version 188 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

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

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