UniProtKB - P15428 (PGDH_HUMAN)
15-hydroxyprostaglandin dehydrogenase [NAD(+)]
HPGD
Functioni
Catalyzes the NAD-dependent dehydrogenation (oxidation) of a broad array of hydroxylated polyunsaturated fatty acids (mainly eicosanoids and docosanoids, including prostaglandins, lipoxins and resolvins), yielding their corresponding keto (oxo) metabolites (PubMed:8086429, PubMed:10837478, PubMed:16828555, PubMed:16757471, PubMed:21916491, PubMed:25586183).
Decreases the levels of the pro-proliferative prostaglandins such as prostaglandin E2 (whose activity is increased in cancer because of an increase in the expression of cyclooxygenase 2) and generates oxo-fatty acid products that can profoundly influence cell function by abrogating pro-inflammatory cytokine expression (PubMed:25586183, PubMed:15574495).
Converts resolvins E1, D1 and D2 to their oxo products, which represents a mode of resolvin inactivation. Resolvin E1 plays important roles during the resolution phase of acute inflammation, while resolvins D1 and D2 have a unique role in obesity-induced adipose inflammation (PubMed:16757471, PubMed:22844113).
8 PublicationsCatalytic activityi
- EC:1.1.1.1416 PublicationsThis reaction proceeds in the forward3 Publications direction.
- (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + NAD+ = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H+ + NADH1 PublicationEC:1.1.1.2321 PublicationThis reaction proceeds in the forward1 Publication direction.
- (11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoate + NAD+ = 11-oxo-(5Z,8Z,12E,14Z)-eicosatetraenoate + H+ + NADH1 PublicationThis reaction proceeds in the forward1 Publication direction.
- lipoxin A4 + NAD+ = 15-oxo-(5S,6R)-dihydroxy-(7E,9E,11Z,13E)-eicosatetraenoate + H+ + NADH1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 15-oxo-(5S,6R)-dihydroxy-(7E,9E,11Z)-eicosatrienoate + H+ + NADH = (5S,6R,15S)-trihydroxy-(7E,9E,11Z)-eicosatrienoate + NAD+1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- 14-hydroxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate + NAD+ = 14-oxo-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate + H+ + NADH1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Kineticsi
- KM=3.4 µM for prostaglandin E22 Publications
- KM=5.5 µM for prostaglandin E11 Publication
- KM=4.5 µM for prostaglandin A11 Publication
- KM=22 µM for prostaglandin A21 Publication
- KM=3.42 µM for (11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoate1 Publication
- KM=1.65 µM for (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate1 Publication
- KM=22 µM for NAD in the presence of prostaglandin E11 Publication
- KM=38 µM for NAD in the presence of prostaglandin E21 Publication
- Vmax=296 nmol/min/mg enzyme toward (11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoate1 Publication
- Vmax=403.8 nmol/min/mg enzyme toward (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate1 Publication
- Vmax=13.1 µmol/min/mg enzyme toward prostaglandin A21 Publication
- Vmax=21.58 µmol/min/mg enzyme toward prostaglandin A11 Publication
- Vmax=24.98 µmol/min/mg enzyme toward NAD in the presence of prostaglandin E11 Publication
- Vmax=22.8 µmol/min/mg enzyme toward prostaglandin E11 Publication
- Vmax=24.6 µmol/min/mg enzyme toward prostaglandin E21 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 91 | NAD; via carbonyl oxygen1 Publication | 1 | |
Binding sitei | 138 | SubstrateCurated | 1 | |
Binding sitei | 148 | SubstrateCurated | 1 | |
Active sitei | 151 | Proton acceptor | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 12 – 20 | NAD1 Publication | 9 | |
Nucleotide bindingi | 36 – 37 | NAD1 Publication | 2 | |
Nucleotide bindingi | 63 – 65 | NAD1 Publication | 3 | |
Nucleotide bindingi | 151 – 155 | NAD1 Publication | 5 | |
Nucleotide bindingi | 186 – 188 | NAD1 Publication | 3 |
GO - Molecular functioni
- 15-hydroxyprostaglandin dehydrogenase (NAD+) activity Source: UniProtKB
- identical protein binding Source: UniProtKB
- NAD+ binding Source: UniProtKB
- NAD binding Source: UniProtKB
- oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Source: UniProtKB
- prostaglandin E receptor activity Source: UniProtKB
GO - Biological processi
- ductus arteriosus closure Source: UniProtKB
- female pregnancy Source: UniProtKB
- kidney development Source: Ensembl
- lipoxygenase pathway Source: UniProtKB
- negative regulation of cell cycle Source: UniProtKB
- ovulation Source: UniProtKB
- parturition Source: UniProtKB
- positive regulation of apoptotic process Source: Ensembl
- positive regulation of vascular associated smooth muscle cell proliferation Source: Ensembl
- prostaglandin metabolic process Source: UniProtKB
- regulation of prostaglandin catabolic process Source: UniProtKB
- response to estradiol Source: Ensembl
- response to ethanol Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- thrombin-activated receptor signaling pathway Source: UniProtKB
- transforming growth factor beta receptor signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Fatty acid metabolism, Lipid metabolism, Prostaglandin metabolism |
Ligand | NAD |
Enzyme and pathway databases
BRENDAi | 1.1.1.141, 2681 1.3.1.48, 2681 |
PathwayCommonsi | P15428 |
Reactomei | R-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-RKi | P15428 |
SignaLinki | P15428 |
SIGNORi | P15428 |
Chemistry databases
SwissLipidsi | SLP:000000732 |
Names & Taxonomyi
Protein namesi | Recommended name: 15-hydroxyprostaglandin dehydrogenase [NAD(+)]Curated (EC:1.1.1.1416 Publications)Short name: 15-PGDH Alternative name(s): |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5154, HPGD |
MIMi | 601688, gene |
neXtProti | NX_P15428 |
VEuPathDBi | HostDB:ENSG00000164120 |
Subcellular locationi
Cytoplasm and Cytosol
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- basolateral plasma membrane Source: Ensembl
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (PHOAR1)1 Publication
Cranioosteoarthropathy (COA)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_046209 | 140 | A → P in COA; inactive. 1 PublicationCorresponds to variant dbSNP:rs121434480EnsemblClinVar. | 1 |
Digital clubbing, isolated congenital (DIGC)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_060792 | 193 | S → P in DIGC. 1 PublicationCorresponds to variant dbSNP:rs121434481EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 148 | Q → A: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 148 | Q → E, H or N: Reduced affinity for NAD and prostaglandin E2. 1 Publication | 1 | |
Mutagenesisi | 151 | Y → A: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 151 | Y → F: Loss 15-hydroxyprostaglandin dehydrogenase activity. 1 Publication | 1 | |
Mutagenesisi | 155 | K → Q: Loss 15-hydroxyprostaglandin dehydrogenase activity. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Tumor suppressorOrganism-specific databases
DisGeNETi | 3248 |
MalaCardsi | HPGD |
MIMi | 119900, phenotype 259100, phenotype |
OpenTargetsi | ENSG00000164120 |
Orphaneti | 1525, Cranio-osteoarthropathy 217059, Isolated congenital digital clubbing 2796, Pachydermoperiostosis |
PharmGKBi | PA29424 |
Miscellaneous databases
Pharosi | P15428, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1293255 |
DrugBanki | DB00157, NADH |
GuidetoPHARMACOLOGYi | 1384 |
Genetic variation databases
BioMutai | HPGD |
DMDMi | 129889 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000054744 | 1 – 266 | 15-hydroxyprostaglandin dehydrogenase [NAD(+)]Add BLAST | 266 |
Proteomic databases
EPDi | P15428 |
jPOSTi | P15428 |
MassIVEi | P15428 |
MaxQBi | P15428 |
PaxDbi | P15428 |
PeptideAtlasi | P15428 |
PRIDEi | P15428 |
ProteomicsDBi | 18546 48016 5156 53141 [P15428-1] 53142 [P15428-2] |
2D gel databases
SWISS-2DPAGEi | P15428 |
PTM databases
iPTMneti | P15428 |
PhosphoSitePlusi | P15428 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000164120, Expressed in metanephros and 190 other tissues |
ExpressionAtlasi | P15428, baseline and differential |
Genevisiblei | P15428, HS |
Organism-specific databases
HPAi | ENSG00000164120, Tissue enhanced (stomach, urinary bladder) |
Interactioni
Subunit structurei
Homodimer.
1 PublicationGO - Molecular functioni
- identical protein binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 109485, 12 interactors |
STRINGi | 9606.ENSP00000296522 |
Chemistry databases
BindingDBi | P15428 |
Miscellaneous databases
RNActi | P15428, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P15428 |
SMRi | P15428 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P15428 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG4169, Eukaryota |
GeneTreei | ENSGT00940000154593 |
HOGENOMi | CLU_010194_2_19_1 |
InParanoidi | P15428 |
OMAi | QGIHFQN |
OrthoDBi | 1053465at2759 |
PhylomeDBi | P15428 |
TreeFami | TF324093 |
Family and domain databases
InterProi | View protein in InterPro IPR036291, NAD(P)-bd_dom_sf IPR020904, Sc_DH/Rdtase_CS IPR002347, SDR_fam |
Pfami | View protein in Pfam PF00106, adh_short, 1 hit |
PRINTSi | PR00081, GDHRDH PR00080, SDRFAMILY |
SUPFAMi | SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS00061, ADH_SHORT, 1 hit |
s (5+)i Sequence
Sequence statusi: Complete.
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD6RA66 | D6RA66_HUMAN | 15-hydroxyprostaglandin dehydrogena... | HPGD | 97 | Annotation score: | ||
D6RA83 | D6RA83_HUMAN | 15-hydroxyprostaglandin dehydrogena... | HPGD | 99 | Annotation score: | ||
E9PBZ2 | E9PBZ2_HUMAN | 15-hydroxyprostaglandin dehydrogena... | HPGD | 176 | Annotation score: | ||
D6RHF8 | D6RHF8_HUMAN | 15-hydroxyprostaglandin dehydrogena... | HPGD | 37 | Annotation score: | ||
E9PD69 | E9PD69_HUMAN | 15-hydroxyprostaglandin dehydrogena... | HPGD | 87 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 50 | D → H in AAA89175 (PubMed:1697582).Curated | 1 | |
Sequence conflicti | 50 | D → H in AAA89174 (PubMed:1697582).Curated | 1 | |
Sequence conflicti | 97 | E → K in CAA57843 (PubMed:7557451).Curated | 1 | |
Sequence conflicti | 219 | I → V in BAG61916 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_046209 | 140 | A → P in COA; inactive. 1 PublicationCorresponds to variant dbSNP:rs121434480EnsemblClinVar. | 1 | |
Natural variantiVAR_060792 | 193 | S → P in DIGC. 1 PublicationCorresponds to variant dbSNP:rs121434481EnsemblClinVar. | 1 | |
Natural variantiVAR_006972 | 217 | Y → C. Corresponds to variant dbSNP:rs140209262Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045106 | 1 – 121 | Missing in isoform 3. 1 PublicationAdd BLAST | 121 | |
Alternative sequenceiVSP_045579 | 73 – 140 | Missing in isoform 5. 1 PublicationAdd BLAST | 68 | |
Alternative sequenceiVSP_045107 | 140 – 143 | AGLM → AAHH in isoform 4. 1 Publication | 4 | |
Alternative sequenceiVSP_045108 | 144 – 266 | Missing in isoform 4. 1 PublicationAdd BLAST | 123 | |
Alternative sequenceiVSP_043032 | 167 – 266 | LAANL…QAKTQ → PTIDCQWIDNTH in isoform 2. 2 PublicationsAdd BLAST | 100 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000296521.11; ENSP00000296521.7; ENSG00000164120.14 [P15428-2] ENST00000296522.11; ENSP00000296522.6; ENSG00000164120.14 ENST00000422112.6; ENSP00000398720.2; ENSG00000164120.14 [P15428-5] ENST00000510901.5; ENSP00000422418.1; ENSG00000164120.14 [P15428-3] ENST00000541923.5; ENSP00000438017.1; ENSG00000164120.14 [P15428-3] ENST00000542498.5; ENSP00000443644.1; ENSG00000164120.14 [P15428-4] |
GeneIDi | 3248 |
KEGGi | hsa:3248 |
MANE-Selecti | ENST00000296522.11; ENSP00000296522.6; NM_000860.6; NP_000851.2 |
UCSCi | uc003itu.3, human [P15428-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
SeattleSNPs |
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2GDZ | X-ray | 1.65 | A | 3-256 | [»] | |
AlphaFoldDBi | P15428 | |||||
SMRi | P15428 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109485, 12 interactors |
STRINGi | 9606.ENSP00000296522 |
Chemistry databases
BindingDBi | P15428 |
ChEMBLi | CHEMBL1293255 |
DrugBanki | DB00157, NADH |
GuidetoPHARMACOLOGYi | 1384 |
SwissLipidsi | SLP:000000732 |
PTM databases
iPTMneti | P15428 |
PhosphoSitePlusi | P15428 |
Genetic variation databases
BioMutai | HPGD |
DMDMi | 129889 |
2D gel databases
SWISS-2DPAGEi | P15428 |
Proteomic databases
EPDi | P15428 |
jPOSTi | P15428 |
MassIVEi | P15428 |
MaxQBi | P15428 |
PaxDbi | P15428 |
PeptideAtlasi | P15428 |
PRIDEi | P15428 |
ProteomicsDBi | 18546 48016 5156 53141 [P15428-1] 53142 [P15428-2] |
Protocols and materials databases
Antibodypediai | 1511, 561 antibodies from 38 providers |
DNASUi | 3248 |
Genome annotation databases
Organism-specific databases
CTDi | 3248 |
DisGeNETi | 3248 |
GeneCardsi | HPGD |
HGNCi | HGNC:5154, HPGD |
HPAi | ENSG00000164120, Tissue enhanced (stomach, urinary bladder) |
MalaCardsi | HPGD |
MIMi | 119900, phenotype 259100, phenotype 601688, gene |
neXtProti | NX_P15428 |
OpenTargetsi | ENSG00000164120 |
Orphaneti | 1525, Cranio-osteoarthropathy 217059, Isolated congenital digital clubbing 2796, Pachydermoperiostosis |
PharmGKBi | PA29424 |
VEuPathDBi | HostDB:ENSG00000164120 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4169, Eukaryota |
GeneTreei | ENSGT00940000154593 |
HOGENOMi | CLU_010194_2_19_1 |
InParanoidi | P15428 |
OMAi | QGIHFQN |
OrthoDBi | 1053465at2759 |
PhylomeDBi | P15428 |
TreeFami | TF324093 |
Enzyme and pathway databases
BRENDAi | 1.1.1.141, 2681 1.3.1.48, 2681 |
PathwayCommonsi | P15428 |
Reactomei | R-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-RKi | P15428 |
SignaLinki | P15428 |
SIGNORi | P15428 |
Miscellaneous databases
BioGRID-ORCSi | 3248, 12 hits in 1082 CRISPR screens |
ChiTaRSi | HPGD, human |
EvolutionaryTracei | P15428 |
GeneWikii | HPGD |
GenomeRNAii | 3248 |
Pharosi | P15428, Tchem |
PROi | PR:P15428 |
RNActi | P15428, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164120, Expressed in metanephros and 190 other tissues |
ExpressionAtlasi | P15428, baseline and differential |
Genevisiblei | P15428, HS |
Family and domain databases
InterProi | View protein in InterPro IPR036291, NAD(P)-bd_dom_sf IPR020904, Sc_DH/Rdtase_CS IPR002347, SDR_fam |
Pfami | View protein in Pfam PF00106, adh_short, 1 hit |
PRINTSi | PR00081, GDHRDH PR00080, SDRFAMILY |
SUPFAMi | SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS00061, ADH_SHORT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PGDH_HUMAN | |
Accessioni | P15428Primary (citable) accession number: P15428 Secondary accession number(s): B4DTA4 Q12998 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1990 |
Last sequence update: | April 1, 1990 | |
Last modified: | May 25, 2022 | |
This is version 210 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families