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UniProtKB/Swiss-Prot entry P15428


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name PGDH_HUMAN
Primary accession number P15428
Secondary accession number Q06F08
Integrated into Swiss-Prot on April 1, 1990
Sequence was last modified on April 1, 1990 (Sequence version 1)
Annotations were last modified on    June 16, 2009 (Entry version 96)
Name and origin of the protein
Protein name 15-hydroxyprostaglandin dehydrogenase [NAD+]
Synonyms PGDH
EC 1.1.1.141
Prostaglandin dehydrogenase 1
Gene name
Name: HPGD
Synonyms: PGDH1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
PROTEIN SEQUENCE.
TISSUE=Placenta;
DOI=10.1021/bi00455a021; PubMed=2337593 [NCBI, ExPASy, EBI, Israel, Japan]
Krook M., Marekov L., Joernvall H.;
"Purification and structural characterization of placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family.";
Biochemistry 29:738-743(1990).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Placenta;
PubMed=1697582 [NCBI, ExPASy, EBI, Israel, Japan]
Ensor C.M., Yang J.Y., Okita R.T., Tai H.-H.;
"Cloning and sequence analysis of the cDNA for human placental NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase.";
J. Biol. Chem. 265:14888-14891(1990).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Placenta;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
SeattleSNPs variation discovery resource;
Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Pancreas;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
MUTAGENESIS OF TYR-151.
DOI=10.1016/S0006-291X(05)80262-1; PubMed=2025296 [NCBI, ExPASy, EBI, Israel, Japan]
Ensor C.M., Tai H.-H.;
"Site-directed mutagenesis of the conserved tyrosine 151 of human placental NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase yields a catalytically inactive enzyme.";
Biochem. Biophys. Res. Commun. 176:840-845(1991).
[8]
3D-STRUCTURE MODELING.
DOI=10.1016/0014-5793(93)81554-D; PubMed=8482380 [NCBI, ExPASy, EBI, Israel, Japan]
Krook M., Ghosh D., Duax W.L., Joernvall H.;
"Three-dimensional model of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase and relationships to the NADP(+)-dependent enzyme (carbonyl reductase).";
FEBS Lett. 322:139-142(1993).
[9]
INVOLVEMENT IN PHOAR, VARIANT COA PRO-140, AND CHARACTERIZATION OF VARIANT COA PRO-140.
DOI=10.1038/ng.153; PubMed=18500342 [NCBI, ExPASy, EBI, Israel, Japan]
Uppal S., Diggle C.P., Carr I.M., Fishwick C.W.G., Ahmed M., Ibrahim G.H., Helliwell P.S., Latos-Bielenska A., Phillips S.E.V., Markham A.F., Bennett C.P., Bonthron D.T.;
"Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy.";
Nat. Genet. 40:789-793(2008).
[10]
ERRATUM.
Uppal S., Diggle C.P., Carr I.M., Fishwick C.W.G., Ahmed M., Ibrahim G.H., Helliwell P.S., Latos-Bielenska A., Phillips S.E.V., Markham A.F., Bennett C.P., Bonthron D.T.;
Nat. Genet. 40:927-927(2008).
Comments
  • FUNCTION: Inactivation of prostaglandins.
  • CATALYTIC ACTIVITY: (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.
  • SUBUNIT: Homodimer.
  • SUBCELLULAR LOCATION: Cytoplasm.
  • DISEASE: Defects in HPGD are the cause of primary hypertrophic osteoathropathy autosomal recessive (PHOAR) [MIM:259100]; also known as pachydermoperiostosis autosomal recessive. Primary hypertrophic osteoarthropathy is characterized by digital clubbing, osterarthropathy, variable features of pachydermia, delayed closure of the fontanels, and congenital heart disease.
  • DISEASE: Defects in HPGD are the cause of cranioosteoarthropathy (COA) [MIM:259100]. Clinical features include infantile onset of swelling of the joints, digital clubbing, hyperhidrosis, delayed closure of the fontanels, periostosis, and variable patent ductus arteriosus. Pachydermia is not a prominent feature.
  • SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
  • WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/hpgd/";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
L76465; AAA89175.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J05594; AAA89174.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK314624; BAG37190.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ903072; ABI75347.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CH471056; EAX04734.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC018986; AAH18986.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00305286; -.
PIR A35802; A35802.
RefSeq NP_000851.2; -.
UniGene Hs.655491
3D structure databases
PDB
2GDZ; X-ray; 1.65 A; A=3-256.[ExPASy / RCSB / EBI]
PDBsum 2GDZ; -.
ModBase P15428.
Enzyme and pathway databases
BRENDA 1.1.1.141; 247.
2D gel databases
SWISS-2DPAGE P15428; -.
Siena-2DPAGE P15428; -.
Organism-specific databases
GeneCards GC04M175647; -.
H-InvDB HIX0004645; -.
HGNC HGNC:5154; HPGD.
GenAtlas HPGD.
HPA HPA004919; -.
HPA005679; -.
MIM 259100; phenotype. [NCBI / EBI]
601688; gene. [NCBI / EBI]
Orphanet 1525; Cranio osteoarthropathy.
PharmGKB PA29424; -.
Gene expression databases
ArrayExpress P15428; -.
Bgee P15428; -.
CleanEx HS_HPGD; -.
GermOnline ENSG00000164120; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (traceable author statement from UniProtKB).
GO:0005634; Cellular component: nucleus (inferred from direct assay from HPA).
GO:0016404; Molecular function: 15-hydroxyprostaglandin dehydrogenase (NAD+) activity (inferred from direct assay from UniProtKB).
GO:0051287; Molecular function: NAD or NADH binding (inferred from direct assay from UniProtKB).
GO:0004957; Molecular function: prostaglandin E receptor activity (inferred from direct assay from UniProtKB).
GO:0042803; Molecular function: protein homodimerization activity (traceable author statement from UniProtKB).
GO:0007565; Biological process: female pregnancy (inferred from direct assay from UniProtKB).
GO:0019372; Biological process: lipoxygenase pathway (traceable author statement from UniProtKB).
GO:0045786; Biological process: negative regulation of cell cycle (inferred from direct assay from UniProtKB).
GO:0055114; Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0007567; Biological process: parturition (inferred from direct assay from UniProtKB).
GO:0006693; Biological process: prostaglandin metabolic process (traceable author statement from UniProtKB).
GO:0007179; Biological process: transforming growth factor beta receptor signaling pathway (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR002198; DH_sc/Rdtase_SDR.
IPR002347; Glc/ribitol_DH.
IPR016040; NAD(P)-bd_dom.
Graphical view of domain structure.
Gene3D G3DSA:3.40.50.720; NAD(P)-bd; 1.
PANTHER PTHR19410; ADH_short_C2; 1.
Pfam PF00106; adh_short; 1.
Pfam graphical view of domain structure.
PRINTS PR00081; GDHRDH.
PR00080; SDRFAMILY.
PROSITE PS00061; ADH_SHORT; 1.
Proteomic databases
PRIDE P15428; -.
Genome annotation databases
Ensembl ENSG00000164120; Homo sapiens. [Contig view]
GeneID 3248; -.
KEGG hsa:3248; -.
Phylogenomic databases
HOGENOM P15428; -.
HOVERGEN P15428; -.
OMA P15428; DPSMIAN.
Other
DrugBank DB00157; NADH.
NextBio 12913; -.
SOURCE HPGD; Homo sapiens.
ProtoNet P15428.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Cytoplasm; Direct protein sequencing; Disease mutation; Fatty acid metabolism; Lipid metabolism; NAD; Oxidoreductase; Polymorphism; Prostaglandin metabolism.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
CHAIN   1   266  266     15-hydroxyprostaglandin dehydrogenase [NAD+]. PRO_0000054744
NP_BIND   10    34  25     NAD (By similarity). 
ACT_SITE   151   151        Proton acceptor. 
BINDING   138   138        Substrate (By similarity). 
VARIANT   140   140  1     A -> P (in COA; inactive). VAR_046209 
VARIANT   217   217  1     Y -> C. VAR_006972 
MUTAGEN   151   151        Y->A: Loss of activity. 
CONFLICT   50    50        D -> H (in Ref. 2; AAA89175/AAA89174). 
STRAND   7    11  5      
TURN   12    14  3      
HELIX   16    27  12      
STRAND   31    37  7      
HELIX   39    49  11      
TURN   50    52  3      
HELIX   55    57  3      
STRAND   58    62  5      
HELIX   68    82  15      
STRAND   87    90  4      
STRAND   97    99  3      
HELIX   100   107  8      
HELIX   109   122  14      
HELIX   124   126  3      
STRAND   131   136  6      
HELIX   139   141  3      
HELIX   149   172  24      
STRAND   176   184  9      
STRAND   186   188  3      
HELIX   189   192  4      
HELIX   193   195  3      
HELIX   197   200  4      
HELIX   201   206  6      
HELIX   207   217  11      
HELIX   222   234  13      
STRAND   242   246  5      
TURN   247   249  3      
STRAND   250   253  4      
Sequence information
Length: 266 AA [This is the length of the unprocessed precursor] Molecular weight: 28977 Da [This is the MW of the unprocessed precursor] CRC64: B860D2DE80E49514 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MHVNGKVALV TGAAQGIGRA FAEALLLKGA KVALVDWNLE AGVQCKAALD EQFEPQKTLF 

        70         80         90        100        110        120 
IQCDVADQQQ LRDTFRKVVD HFGRLDILVN NAGVNNEKNW EKTLQINLVS VISGTYLGLD 

       130        140        150        160        170        180 
YMSKQNGGEG GIIINMSSLA GLMPVAQQPV YCASKHGIVG FTRSAALAAN LMNSGVRLNA 

       190        200        210        220        230        240 
ICPGFVNTAI LESIEKEENM GQYIEYKDHI KDMIKYYGIL DPPLIANGLI TLIEDDALNG 

       250        260 
AIMKITTSKG IHFQDYDTTP FQAKTQ 

P15428 in FASTA format

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