ID PTGR1_HUMAN Reviewed; 329 AA.
AC Q14914; A8K0N2; B4DPK3; F5GY50; Q8IYQ0; Q9H1X6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 24-JAN-2024, entry version 207.
DE RecName: Full=Prostaglandin reductase 1 {ECO:0000303|PubMed:25619643};
DE Short=PRG-1 {ECO:0000303|PubMed:25619643};
DE AltName: Full=15-oxoprostaglandin 13-reductase {ECO:0000250|UniProtKB:Q29073};
DE EC=1.3.1.48 {ECO:0000269|PubMed:25619643};
DE AltName: Full=Dithiolethione-inducible gene 1 protein {ECO:0000250|UniProtKB:P97584};
DE Short=D3T-inducible gene 1 protein {ECO:0000250|UniProtKB:P97584};
DE Short=DIG-1 {ECO:0000250|UniProtKB:P97584};
DE AltName: Full=Leukotriene B4 12-hydroxydehydrogenase {ECO:0000303|PubMed:25619643};
DE AltName: Full=NAD(P)H-dependent alkenal/one oxidoreductase {ECO:0000303|PubMed:25619643};
DE EC=1.3.1.74 {ECO:0000269|PubMed:25619643};
GN Name=PTGR1; Synonyms=LTB4DH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP SER-27.
RC TISSUE=Brain cortex, and Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-27.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-27.
RC TISSUE=Cervix;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-311 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=8576264; DOI=10.1074/jbc.271.5.2844;
RA Yokomizo T., Ogawa Y., Uozumi N., Kume K., Izumi T., Shimizu T.;
RT "cDNA cloning, expression, and mutagenesis study of leukotriene B4 12-
RT hydroxydehydrogenase.";
RL J. Biol. Chem. 271:2844-2850(1996).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-18 AND SER-20, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF ARG-56 AND TYR-245.
RX PubMed=25619643; DOI=10.1016/j.cbi.2015.01.021;
RA Mesa J., Alsina C., Oppermann U., Pares X., Farres J., Porte S.;
RT "Human prostaglandin reductase 1 (PGR1): Substrate specificity, inhibitor
RT analysis and site-directed mutagenesis.";
RL Chem. Biol. Interact. 234:105-113(2015).
RN [9]
RP HYDROXYBUTYRYLATION AT LYS-178.
RX PubMed=29192674; DOI=10.1038/cr.2017.149;
RA Huang H., Luo Z., Qi S., Huang J., Xu P., Wang X., Gao L., Li F., Wang J.,
RA Zhao W., Gu W., Chen Z., Dai L., Dai J., Zhao Y.;
RT "Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation
RT pathway.";
RL Cell Res. 28:111-125(2018).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 4-239.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human NADP-dependent leukotriene B4 12-
RT hydroxydehydrogenase.";
RL Submitted (MAY-2005) to the PDB data bank.
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 4-329 IN COMPLEX WITH NADP AND
RP RALOXIFENE.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human leukotriene B4 12-hydroxydehydrogenase in
RT complex with NADP and raloxifene.";
RL Submitted (JAN-2011) to the PDB data bank.
CC -!- FUNCTION: NAD(P)H-dependent oxidoreductase involved in metabolic
CC inactivation of pro- and anti-inflammatory eicosanoids: prostaglandins
CC (PG), leukotrienes (LT) and lipoxins (LX) (PubMed:25619643). Catalyzes
CC with high efficiency the reduction of the 13,14 double bond of 15-
CC oxoPGs, including 15-oxo-PGE1, 15-oxo-PGE2, 15-oxo-PGF1-alpha and 15-
CC oxo-PGF2-alpha (PubMed:25619643). Catalyzes with lower efficiency the
CC oxidation of the hydroxyl group at C12 of LTB4 and its derivatives,
CC converting them into biologically less active 12-oxo-LTB4 metabolites
CC (PubMed:25619643) (By similarity). Reduces 15-oxo-LXA4 to 13,14
CC dihydro-15-oxo-LXA4, enhancing neutrophil recruitment at the
CC inflammatory site (By similarity). May play a role in metabolic
CC detoxification of alkenals and ketones. Reduces alpha,beta-unsaturated
CC alkenals and ketones, particularly those with medium-chain length,
CC showing highest affinity toward (2E)-decenal and (3E)-3-nonen-2-one
CC (PubMed:25619643). May inactivate 4-hydroxy-2-nonenal, a cytotoxic
CC lipid constituent of oxidized low-density lipoprotein particles (By
CC similarity). {ECO:0000250|UniProtKB:P97584,
CC ECO:0000250|UniProtKB:Q29073, ECO:0000269|PubMed:25619643}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13,14-dihydro-15-oxo-prostaglandin E1 + NADP(+) = 15-
CC oxoprostaglandin E1 + H(+) + NADPH; Xref=Rhea:RHEA:50584,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57401, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:133408;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50586;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13,14-dihydro-15-oxo-prostaglandin E2 + NADP(+) = 15-
CC oxoprostaglandin E2 + H(+) + NADPH; Xref=Rhea:RHEA:11912,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57400, ChEBI:CHEBI:57402,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.48;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11914;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13,14-dihydro-15-oxo-prostaglandin F1alpha + NADP(+) = 15-
CC oxoprostaglandin F1alpha + H(+) + NADPH; Xref=Rhea:RHEA:50592,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:79072, ChEBI:CHEBI:133411;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50594;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13,14-dihydro-15-oxo-PGF2alpha + NADP(+) = 15-oxoprostaglandin
CC F2alpha + H(+) + NADPH; Xref=Rhea:RHEA:50588, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133374,
CC ChEBI:CHEBI:133409; Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50590;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=leukotriene B4 + NADP(+) = 12-oxo-leukotriene B4 + H(+) +
CC NADPH; Xref=Rhea:RHEA:50608, ChEBI:CHEBI:15378, ChEBI:CHEBI:57461,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133309;
CC Evidence={ECO:0000250|UniProtKB:Q29073,
CC ECO:0000250|UniProtKB:Q9EQZ5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50609;
CC Evidence={ECO:0000250|UniProtKB:Q29073,
CC ECO:0000250|UniProtKB:Q9EQZ5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20-hydroxy-leukotriene B4 + NADP(+) = 12-oxo-20-hydroxy-
CC leukotriene B4 + H(+) + NADPH; Xref=Rhea:RHEA:51208,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57460, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:133346;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51209;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-trans-leukotriene B4 + NADP(+) = 12-oxo-(5S)-hydroxy-
CC (6E,8E,10E,14Z)-eicosatetraenoate + H(+) + NADPH;
CC Xref=Rhea:RHEA:51204, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:90723, ChEBI:CHEBI:133974;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51205;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S,12S)-dihydroxy-(6E,10E,12E,14Z)-eicosatetraenoate +
CC NADP(+) = 12-oxo-(5S)-hydroxy-(6E,8E,10E,14Z)-eicosatetraenoate +
CC H(+) + NADPH; Xref=Rhea:RHEA:51212, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133974,
CC ChEBI:CHEBI:133975; Evidence={ECO:0000250|UniProtKB:Q29073};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51213;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an n-alkanal + NADP(+) = an alk-2-enal + H(+) + NADPH;
CC Xref=Rhea:RHEA:13737, ChEBI:CHEBI:12834, ChEBI:CHEBI:13757,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.74;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:13739;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexanal + NADP(+) = (E)-hex-2-enal + H(+) + NADPH;
CC Xref=Rhea:RHEA:50776, ChEBI:CHEBI:15378, ChEBI:CHEBI:28913,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:88528;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50778;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + octanal = (2E)-octenal + H(+) + NADPH;
CC Xref=Rhea:RHEA:50780, ChEBI:CHEBI:15378, ChEBI:CHEBI:17935,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:61748;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50782;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanal + NADP(+) = (2E)-decenal + H(+) + NADPH;
CC Xref=Rhea:RHEA:50612, ChEBI:CHEBI:15378, ChEBI:CHEBI:31457,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133455;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50614;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanal + NADP(+) = (2E)-dodecenal + H(+) + NADPH;
CC Xref=Rhea:RHEA:50784, ChEBI:CHEBI:15378, ChEBI:CHEBI:27836,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133741;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50786;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxynonanal + NADP(+) = (E)-4-hydroxynon-2-enal + H(+) +
CC NADPH; Xref=Rhea:RHEA:64736, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:58968, ChEBI:CHEBI:156112;
CC Evidence={ECO:0000250|UniProtKB:P97584};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64738;
CC Evidence={ECO:0000250|UniProtKB:P97584};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + pentan-2-one = (E)-pent-3-en-2-one + H(+) + NADPH;
CC Xref=Rhea:RHEA:50788, ChEBI:CHEBI:15378, ChEBI:CHEBI:16472,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:145276;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50790;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + nonan-2-one = (3E)-nonen-2-one + H(+) + NADPH;
CC Xref=Rhea:RHEA:50616, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:77927, ChEBI:CHEBI:133457;
CC Evidence={ECO:0000269|PubMed:25619643};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50618;
CC Evidence={ECO:0000305|PubMed:25619643};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=33 uM for (2E)-hexenal {ECO:0000269|PubMed:25619643};
CC KM=14 uM for (2E)-octenal {ECO:0000269|PubMed:25619643};
CC KM=6 uM for (2E)-decenal {ECO:0000269|PubMed:25619643};
CC KM=12 uM for (2E)-dodecenal {ECO:0000269|PubMed:25619643};
CC KM=12 uM for (3E)-3-buten-2-one {ECO:0000269|PubMed:25619643};
CC KM=7.3 uM for (3E)-3-penten-2-one {ECO:0000269|PubMed:25619643};
CC KM=6.5 uM for (3E)-3-nonen-2-one {ECO:0000269|PubMed:25619643};
CC KM=1.4 uM for 15-oxoprostaglandin E1 {ECO:0000269|PubMed:25619643};
CC KM=0.6 uM for 15-oxoprostaglandin E2 {ECO:0000269|PubMed:25619643};
CC KM=1.1 uM for 15-oxoprostaglandin F1alpha
CC {ECO:0000269|PubMed:25619643};
CC KM=3.2 uM for 15-oxoprostaglandin F2alpha
CC {ECO:0000269|PubMed:25619643};
CC KM=5.2 uM for leukotriene B4 {ECO:0000269|PubMed:25619643};
CC KM=14 uM for NADPH {ECO:0000269|PubMed:25619643};
CC KM=200 uM for NADH {ECO:0000269|PubMed:25619643};
CC -!- SUBUNIT: Monomer or homodimer. {ECO:0000250|UniProtKB:Q9EQZ5}.
CC -!- INTERACTION:
CC Q14914; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2876800, EBI-1055254;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q29073}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14914-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14914-2; Sequence=VSP_044652;
CC -!- TISSUE SPECIFICITY: High expression in the kidney, liver, and intestine
CC but not in leukocytes. {ECO:0000269|PubMed:8576264}.
CC -!- SIMILARITY: Belongs to the NADP-dependent oxidoreductase L4BD family.
CC {ECO:0000305}.
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DR EMBL; AK289597; BAF82286.1; -; mRNA.
DR EMBL; AK298379; BAG60615.1; -; mRNA.
DR EMBL; AL135787; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL159168; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471105; EAW59074.1; -; Genomic_DNA.
DR EMBL; BC035228; AAH35228.1; -; mRNA.
DR EMBL; D49387; BAA08382.1; -; mRNA.
DR CCDS; CCDS55331.1; -. [Q14914-2]
DR CCDS; CCDS6779.1; -. [Q14914-1]
DR RefSeq; NP_001139580.1; NM_001146108.1. [Q14914-1]
DR RefSeq; NP_001139581.1; NM_001146109.1. [Q14914-2]
DR RefSeq; NP_036344.2; NM_012212.3. [Q14914-1]
DR PDB; 1ZSV; X-ray; 2.30 A; A/B/C/D=4-329.
DR PDB; 2Y05; X-ray; 2.20 A; A/B/C/D=4-329.
DR PDBsum; 1ZSV; -.
DR PDBsum; 2Y05; -.
DR AlphaFoldDB; Q14914; -.
DR SMR; Q14914; -.
DR BioGRID; 116604; 55.
DR IntAct; Q14914; 7.
DR STRING; 9606.ENSP00000385763; -.
DR ChEMBL; CHEMBL4295822; -.
DR DrugBank; DB07177; (5E,13E)-11-HYDROXY-9,15-DIOXOPROSTA-5,13-DIEN-1-OIC ACID.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugBank; DB04066; p-Coumaric acid.
DR SwissLipids; SLP:000001629; -.
DR iPTMnet; Q14914; -.
DR MetOSite; Q14914; -.
DR PhosphoSitePlus; Q14914; -.
DR BioMuta; PTGR1; -.
DR DMDM; 23503081; -.
DR EPD; Q14914; -.
DR jPOST; Q14914; -.
DR MassIVE; Q14914; -.
DR MaxQB; Q14914; -.
DR PaxDb; 9606-ENSP00000385763; -.
DR PeptideAtlas; Q14914; -.
DR ProteomicsDB; 24627; -.
DR ProteomicsDB; 60217; -. [Q14914-1]
DR Pumba; Q14914; -.
DR TopDownProteomics; Q14914-1; -. [Q14914-1]
DR Antibodypedia; 29578; 247 antibodies from 28 providers.
DR DNASU; 22949; -.
DR Ensembl; ENST00000309195.9; ENSP00000311572.5; ENSG00000106853.20. [Q14914-1]
DR Ensembl; ENST00000407693.7; ENSP00000385763.2; ENSG00000106853.20. [Q14914-1]
DR Ensembl; ENST00000538962.7; ENSP00000440281.1; ENSG00000106853.20. [Q14914-2]
DR GeneID; 22949; -.
DR KEGG; hsa:22949; -.
DR MANE-Select; ENST00000407693.7; ENSP00000385763.2; NM_001146108.2; NP_001139580.1.
DR UCSC; uc004bfh.3; human. [Q14914-1]
DR AGR; HGNC:18429; -.
DR CTD; 22949; -.
DR DisGeNET; 22949; -.
DR GeneCards; PTGR1; -.
DR HGNC; HGNC:18429; PTGR1.
DR HPA; ENSG00000106853; Tissue enhanced (intestine, liver).
DR MIM; 601274; gene.
DR neXtProt; NX_Q14914; -.
DR OpenTargets; ENSG00000106853; -.
DR PharmGKB; PA162400322; -.
DR VEuPathDB; HostDB:ENSG00000106853; -.
DR eggNOG; KOG1196; Eukaryota.
DR GeneTree; ENSGT00940000154810; -.
DR HOGENOM; CLU_026673_29_3_1; -.
DR InParanoid; Q14914; -.
DR OMA; PIKNIHN; -.
DR OrthoDB; 179761at2759; -.
DR PhylomeDB; Q14914; -.
DR TreeFam; TF324201; -.
DR PathwayCommons; Q14914; -.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-HSA-2142700; Synthesis of Lipoxins (LX).
DR SignaLink; Q14914; -.
DR BioGRID-ORCS; 22949; 14 hits in 1155 CRISPR screens.
DR ChiTaRS; PTGR1; human.
DR EvolutionaryTrace; Q14914; -.
DR GenomeRNAi; 22949; -.
DR Pharos; Q14914; Tbio.
DR PRO; PR:Q14914; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q14914; Protein.
DR Bgee; ENSG00000106853; Expressed in jejunal mucosa and 184 other cell types or tissues.
DR ExpressionAtlas; Q14914; baseline and differential.
DR Genevisible; Q14914; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0036185; F:13-lipoxin reductase activity; ISS:UniProtKB.
DR GO; GO:0036132; F:13-prostaglandin reductase activity; IDA:UniProtKB.
DR GO; GO:0047522; F:15-oxoprostaglandin 13-oxidase activity; IBA:GO_Central.
DR GO; GO:0035798; F:2-alkenal reductase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0097257; F:leukotriene B4 12-hydroxy dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0036102; P:leukotriene B4 metabolic process; ISS:UniProtKB.
DR GO; GO:0006691; P:leukotriene metabolic process; NAS:UniProtKB.
DR GO; GO:2001302; P:lipoxin A4 metabolic process; ISS:UniProtKB.
DR GO; GO:0006693; P:prostaglandin metabolic process; IDA:UniProtKB.
DR CDD; cd08294; leukotriene_B4_DH_like; 1.
DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR041694; ADH_N_2.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR045010; MDR_fam.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR014190; PTGR1.
DR NCBIfam; TIGR02825; B4_12hDH; 1.
DR PANTHER; PTHR43205; PROSTAGLANDIN REDUCTASE; 1.
DR PANTHER; PTHR43205:SF33; PROSTAGLANDIN REDUCTASE 1; 1.
DR Pfam; PF16884; ADH_N_2; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; GroES-like; 2.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Fatty acid metabolism; Hydroxylation; Lipid metabolism; NADP;
KW Oxidoreductase; Phosphoprotein; Prostaglandin metabolism;
KW Reference proteome.
FT CHAIN 1..329
FT /note="Prostaglandin reductase 1"
FT /id="PRO_0000218065"
FT BINDING 152..155
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.11"
FT BINDING 178
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.11"
FT BINDING 193
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.11"
FT BINDING 217
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.11"
FT BINDING 239..245
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.11"
FT BINDING 270..272
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.11"
FT BINDING 321
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.11"
FT MOD_RES 18
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 178
FT /note="N6-(2-hydroxyisobutyryl)lysine; alternate"
FT /evidence="ECO:0000269|PubMed:29192674"
FT MOD_RES 178
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91YR9"
FT VAR_SEQ 294..329
FT /note="GKIQYKEYIIEGFENMPAAFMGMLKGDNLGKTIVKA -> IKRENEED (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044652"
FT VARIANT 27
FT /note="A -> S (in dbSNP:rs1053959)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_023111"
FT MUTAGEN 56
FT /note="R->A: Markedly decreases the catalytic efficiency
FT toward 15-oxoprostaglandin E2."
FT /evidence="ECO:0000269|PubMed:25619643"
FT MUTAGEN 245
FT /note="Y->A,F: Markedly decreases the catalytic efficiency
FT toward 15-oxoprostaglandin E2 and (3E)-3-nonen-2-one."
FT /evidence="ECO:0000269|PubMed:25619643"
FT CONFLICT 311
FT /note="A -> R (in Ref. 5; BAA08382)"
FT /evidence="ECO:0000305"
FT STRAND 4..11
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 22..28
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 37..45
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 49..53
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 67..75
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 91..97
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 115..119
FT /evidence="ECO:0007829|PDB:2Y05"
FT TURN 120..122
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 124..134
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 144..149
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 153..164
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 168..175
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 176..185
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:2Y05"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 199..206
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 211..218
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 220..227
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 230..238
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 242..245
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 257..262
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 277..292
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:2Y05"
FT HELIX 309..317
FT /evidence="ECO:0007829|PDB:2Y05"
FT STRAND 322..328
FT /evidence="ECO:0007829|PDB:2Y05"
SQ SEQUENCE 329 AA; 35870 MW; E121ADB7C5BD9CF8 CRC64;
MVRTKTWTLK KHFVGYPTNS DFELKTAELP PLKNGEVLLE ALFLTVDPYM RVAAKRLKEG
DTMMGQQVAK VVESKNVALP KGTIVLASPG WTTHSISDGK DLEKLLTEWP DTIPLSLALG
TVGMPGLTAY FGLLEICGVK GGETVMVNAA AGAVGSVVGQ IAKLKGCKVV GAVGSDEKVA
YLQKLGFDVV FNYKTVESLE ETLKKASPDG YDCYFDNVGG EFSNTVIGQM KKFGRIAICG
AISTYNRTGP LPPGPPPEIV IYQELRMEAF VVYRWQGDAR QKALKDLLKW VLEGKIQYKE
YIIEGFENMP AAFMGMLKGD NLGKTIVKA
//
