15-hydroxyprostaglandin dehydrogenase [NAD(+)]
Details
- Name
- 15-hydroxyprostaglandin dehydrogenase [NAD(+)]
- Kind
- protein
- Synonyms
- 1.1.1.141
- 15-PGDH
- Eicosanoid/docosanoid dehydrogenase [NAD(+)]
- PGDH1
- Prostaglandin dehydrogenase 1
- SDR36C1
- Short chain dehydrogenase/reductase family 36C member 1
- Gene Name
- HPGD
- UniProtKB Entry
- P15428Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0001102|15-hydroxyprostaglandin dehydrogenase [NAD(+)] MHVNGKVALVTGAAQGIGRAFAEALLLKGAKVALVDWNLEAGVQCKAALDEQFEPQKTLF IQCDVADQQQLRDTFRKVVDHFGRLDILVNNAGVNNEKNWEKTLQINLVSVISGTYLGLD YMSKQNGGEGGIIINMSSLAGLMPVAQQPVYCASKHGIVGFTRSAALAANLMNSGVRLNA ICPGFVNTAILESIEKEENMGQYIEYKDHIKDMIKYYGILDPPLIANGLITLIEDDALNG AIMKITTSKGIHFQDYDTTPFQAKTQ
- Number of residues
- 266
- Molecular Weight
- 28977.105
- Theoretical pI
- 5.65
- GO Classification
- Functionsidentical protein binding / oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptorProcesseskidney development / positive regulation of apoptotic process / positive regulation of vascular associated smooth muscle cell proliferation / regulation of prostaglandin catabolic process / response to estradiol / response to ethanol / response to lipopolysaccharide / thrombin-activated receptor signaling pathway
- General Function
- 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:10837478, PubMed:16757471, PubMed:16828555, PubMed:21916491, PubMed:25586183, PubMed:8086429). 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:15574495, PubMed:25586183). 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)
- Specific Function
- 15-hydroxyprostaglandin dehydrogenase (NAD+) activity
- Pfam Domain Function
- adh_short (PF00106)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasm
- Gene sequence
>lcl|BSEQ0010385|15-hydroxyprostaglandin dehydrogenase [NAD(+)] (HPGD) ATGCACGTGAACGGCAAAGTGGCGCTGGTGACCGGCGCGGCTCAGGGCATAGGCAGAGCC TTTGCAGAGGCGCTGCTGCTTAAGGGCGCCAAGGTAGCGCTGGTGGATTGGAATCTTGAA GCAGGTGTACAGTGTAAAGCTGCCCTGGATGAGCAGTTTGAACCTCAGAAGACTCTGTTC ATCCAGTGCGATGTGGCTGACCAGCAACAACTGAGAGACACTTTTAGAAAAGTTGTAGAC CACTTTGGAAGACTGGACATTTTGGTCAATAATGCTGGAGTGAATAATGAGAAAAACTGG GAAAAAACTCTGCAAATTAATTTGGTTTCTGTTATCAGTGGAACCTATCTTGGTTTGGAT TACATGAGTAAGCAAAATGGAGGTGAAGGCGGCATCATTATCAATATGTCATCTTTAGCA GGACTCATGCCCGTTGCACAGCAGCCGGTTTATTGTGCTTCAAAGCATGGCATAGTTGGA TTCACACGCTCAGCAGCGTTGGCTGCTAATCTTATGAACAGTGGTGTGAGACTGAATGCC ATTTGTCCAGGCTTTGTTAACACAGCCATCCTTGAATCAATTGAAAAAGAAGAAAACATG GGACAATATATAGAATATAAGGATCATATCAAGGATATGATTAAATACTATGGAATTTTG GACCCACCATTGATTGCCAATGGATTGATAACACTCATTGAAGATGATGCTTTAAATGGT GCTATTATGAAGATCACAACTTCTAAGGGAATTCATTTTCAAGACTATGATACAACTCCA TTTCAAGCAAAAACCCAATGA
- Chromosome Location
- 4
- Locus
- 4q34.1
- External Identifiers
Resource Link UniProtKB ID P15428 UniProtKB Entry Name PGDH_HUMAN GenBank Protein ID 1203984 GenBank Gene ID L76465 GeneCard ID HPGD GenAtlas ID HPGD HGNC ID HGNC:5154 PDB ID(s) 2GDZ, 8CVN, 8CWL, 8FD8 KEGG ID hsa:3248 IUPHAR/Guide To Pharmacology ID 1384 NCBI Gene ID 3248 - General References
- Krook M, Marekov L, Jornvall 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. 1990 Jan 23;29(3):738-43. [Article]
- Ensor CM, Yang JY, Okita RT, Tai HH: Cloning and sequence analysis of the cDNA for human placental NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase. J Biol Chem. 1990 Sep 5;265(25):14888-91. [Article]
- Pichaud F, Frendo JL, Delage-Mourroux R, de Vernejoul MC, Moukhtar MS, Jullienne A: Sequence of a novel mRNA coding for a C-terminal-truncated form of human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase. Gene. 1995 Sep 11;162(2):319-22. [Article]
- Delage-Mourroux R, Pichaud F, Frendo JL, Pidoux E, Guliana JM, Moukhtar MS, Jullienne A: Cloning and sequencing of a new 15-hydroxyprostaglandin dehydrogenase related mRNA. Gene. 1997 Mar 25;188(1):143-8. [Article]
- 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 TO, 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. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
- Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Ensor CM, Tai HH: 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. 1991 Apr 30;176(2):840-5. [Article]
- Clish CB, Levy BD, Chiang N, Tai HH, Serhan CN: Oxidoreductases in lipoxin A4 metabolic inactivation: a novel role for 15-onoprostaglandin 13-reductase/leukotriene B4 12-hydroxydehydrogenase in inflammation. J Biol Chem. 2000 Aug 18;275(33):25372-80. [Article]
- Patel FA, Funder JW, Challis JR: Mechanism of cortisol/progesterone antagonism in the regulation of 15-hydroxyprostaglandin dehydrogenase activity and messenger ribonucleic acid levels in human chorion and placental trophoblast cells at term. J Clin Endocrinol Metab. 2003 Jun;88(6):2922-33. [Article]
- Yan M, Rerko RM, Platzer P, Dawson D, Willis J, Tong M, Lawrence E, Lutterbaugh J, Lu S, Willson JK, Luo G, Hensold J, Tai HH, Wilson K, Markowitz SD: 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers. Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17468-73. Epub 2004 Dec 1. [Article]
- Cho H, Huang L, Hamza A, Gao D, Zhan CG, Tai HH: Role of glutamine 148 of human 15-hydroxyprostaglandin dehydrogenase in catalytic oxidation of prostaglandin E2. Bioorg Med Chem. 2006 Oct 1;14(19):6486-91. Epub 2006 Jul 7. [Article]
- Krook M, Ghosh D, Duax W, Jornvall H: Three-dimensional model of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase and relationships to the NADP(+)-dependent enzyme (carbonyl reductase). FEBS Lett. 1993 May 10;322(2):139-42. [Article]
- Uppal S, Diggle CP, Carr IM, Fishwick CW, Ahmed M, Ibrahim GH, Helliwell PS, Latos-Bielenska A, Phillips SE, Markham AF, Bennett CP, Bonthron DT: Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy. Nat Genet. 2008 Jun;40(6):789-93. doi: 10.1038/ng.153. Epub 2008 May 25. [Article]
- Niesen FH, Schultz L, Jadhav A, Bhatia C, Guo K, Maloney DJ, Pilka ES, Wang M, Oppermann U, Heightman TD, Simeonov A: High-affinity inhibitors of human NAD-dependent 15-hydroxyprostaglandin dehydrogenase: mechanisms of inhibition and structure-activity relationships. PLoS One. 2010 Nov 2;5(11):e13719. doi: 10.1371/journal.pone.0013719. [Article]
- Tariq M, Azeem Z, Ali G, Chishti MS, Ahmad W: Mutation in the HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbing (ICNC). J Med Genet. 2009 Jan;46(1):14-20. doi: 10.1136/jmg.2008.061234. Epub 2008 Sep 19. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details NADH approved, nutraceutical unknown target Details Alprostadil approved, investigational unknown enzyme substrate Details