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HPGD

From Wikipedia, the free encyclopedia

HPGD
Identifiers
AliasesHPGD, 15-PGDH, PGDH, PGDH1, PHOAR1, SDR36C1, hydroxyprostaglandin dehydrogenase 15-(NAD), 15-hydroxyprostaglandin dehydrogenase
External IDsOMIM: 601688; MGI: 108085; HomoloGene: 68095; GeneCards: HPGD; OMA:HPGD - orthologs
Available structures
PDBOrtholog search: PDBe RCSB
Enzyme activity
EC #BRENDAExPASyKEGGMetaCyc
1.1.1.141↗↗↗↗
1.1.1.232↗↗↗↗
Orthologs
SpeciesHumanMouse
Entrez

3248

15446

Ensembl

ENSG00000164120

ENSMUSG00000031613

UniProt

P15428

Q8VCC1

RefSeq (mRNA)

NM_008278

RefSeq (protein)

NP_032304

Location (UCSC)Chr 4: 174.49 – 174.52 MbChr 8: 56.75 – 56.77 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Hydroxyprostaglandin dehydrogenase 15-(NAD) (the HUGO-approved official symbol = HPGD; HGNC ID, HGNC:5154), also called 15-hydroxyprostaglandin dehydrogenase [NAD+], is an enzyme that in humans is encoded by the HPGD gene.[5][6]

In melanocytic cells HPGD gene expression may be regulated by MITF.[7]

Tissue distribution

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HPGD RNA-seq was performed in tissue samples from 95 human individuals representing 27 different tissues to determine tissue-specificity of all protein-coding genes.[8] HPGD was expressed in the adrenal, appendix, bone marrow, brain, colon, duodenum, endometrium, esophagus, fat, gall bladder, heart, kidney, liver, lung, lymph node, ovary, pancreas, placenta, prostate, salivary gland, skin, small intestine, spleen, stomach, testis, thyroid, urinary bladder

Function

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15-hydroxy prostaglandin dehydrogenase (HPGD, also referred to as 15-PGDH) is an enzyme belongs to the family of oxidoreductases, specifically the short chain dehydrogenase/reductase family 36C member 1.[9] This protein coding gene encodes a member of the short chain alcohol dehydrogenase protein family.[10] HPGD catalyzes the first step in the catabolic pathway of prostaglandins and is therefore responsible for the metabolic/catabolic inactivation of prostaglandins.[11] This inactivation process will oxidize the 15-hydroxyl group of prostaglandins and yield the corresponding 15-keto (oxo) metabolite.[12]

Prostaglandins have a critical role in the signaling pathways that are involved in reproduction (establishment of pregnancy, maintenance of pregnancy, and initiation of labor), blood pressure homeostasis (vasoconstriction and vasodilation), sexual dimorphism, and the immune system (inflammation).[13][14][15][16][17] HPGD has a critical role in the regulation of prostaglandin expression.

Defects in 15-HPGD

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15-HPGD has an unappreciated role in the maintenance of pregnancy. In mice, 15-HPDG has been shown to have essential roles in prevention of early termination of pregnancy and maternal morbidity.[18] In 15-HPGD knockout mice, early pregnancy termination was detected. 15-HPGD KO mice that were able to establish pregnancy, lost pregnancy by gestation day ~8.5. At time of pregnancy loss, 15-HPGD KO mice have normal levels of PGE2, increased levels of PGF2α and decreasing levels of serum progesterone.[18]

A hypomorphic mutation of 15-HPGD causes mice to enter labor ~ a full day earlier when compared to their wild-type littermates, due to elevated circulating PGF2α concentrations. Furthermore, it was concluded that 15-HPGD has a critical role in determining the timing of labor[19]

See also

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References

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  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000164120 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031613 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, et al. (February 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chemico-Biological Interactions. 178 (1–3): 94–98. Bibcode:2009CBI...178...94P. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
  6. ↑ "Entrez Gene: HPGD hydroxyprostaglandin dehydrogenase 15-(NAD)".
  7. ↑ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, et al. (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–676. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. S2CID 24698373.
  8. ↑ "HPGD Gene Expression - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-04-17.
  9. ↑ "HPGD Gene - GeneCards | PGDH Protein | PGDH Antibody". www.genecards.org. Retrieved 2023-04-17.
  10. ↑ "HPGD 15-hydroxyprostaglandin dehydrogenase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-04-17.
  11. ↑ Parent M, Madore E, MacLaren LA, Fortier MA (March 2006). "15-Hydroxyprostaglandin dehydrogenase in the bovine endometrium during the oestrous cycle and early pregnancy". Reproduction. 131 (3). Cambridge, England: 573–582. doi:10.1530/rep.1.00804. PMID 16514200.
  12. ↑ Ensor CM, Tai HH (September 1994). "Bacterial expression and site-directed mutagenesis of two critical residues (tyrosine-151 and lysine-155) of human placental NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1208 (1): 151–156. doi:10.1016/0167-4838(94)90172-4. PMID 8086429.
  13. ↑ Hizaki H, Segi E, Sugimoto Y, Hirose M, Saji T, Ushikubi F, et al. (August 1999). "Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP(2)". Proceedings of the National Academy of Sciences of the United States of America. 96 (18): 10501–10506. doi:10.1073/pnas.96.18.10501. PMC 17918. PMID 10468638.
  14. ↑ Kobayashi T, Narumiya S (2002). "Function of prostanoid receptors: studies on knockout mice". Prostaglandins & Other Lipid Mediators. 68–69: 557–573. doi:10.1016/s0090-6980(02)00055-2. PMID 12432943.
  15. ↑ Lim H (1997). "Multiple female reproductive failures in cyclooxygenase 2-defcient mice". Cell. 91 (2): 197–208. doi:10.1016/s0092-8674(00)80402-x. PMID 9346237.
  16. ↑ Murata T (1997). "Altered pain perception and infammatory response in mice lacking prostacyclin receptor". Nature. 388 (2): 678–682. doi:10.1016/s0092-8674(00)80402-x. PMID 9346237.
  17. ↑ Thomas DW, Mannon RB, Mannon PJ, Latour A, Oliver JA, Hoffman M, et al. (December 1998). "Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2". The Journal of Clinical Investigation. 102 (11): 1994–2001. doi:10.1172/JCI5116. PMC 509152. PMID 9835625.
  18. 1 2 Roizen JD, Asada M, Tong M, Tai HH, Muglia LJ (November 2019). "Early pregnancy loss in 15-hydroxyprostaglandin dehydrogenase knockout (15-HPGD-/-) mice due to requirement for embryo 15-HPGD activity". Scientific Reports. 9 (1) 17612. doi:10.1038/s41598-019-54064-7. PMC 6879597. PMID 31772225.
  19. ↑ Roizen JD (2008). 15-hydroxyprostaglandin dehydrogenase in mouse pregnancy and parturition (Ph.D. thesis). Washington University in St. Louis.

Further reading

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Retrieved from "https://en.wikipedia.org/w/index.php?title=HPGD&oldid=1359494116"