PTGR3_MOUSE
ID PTGR3_MOUSE Reviewed; 377 AA.
AC Q8BGC4;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Prostaglandin reductase-3 {ECO:0000303|PubMed:23821743};
DE Short=PTGR-3;
DE EC=1.3.1.48 {ECO:0000269|PubMed:23821743};
DE AltName: Full=15-oxoprostaglandin 13-reductase;
DE AltName: Full=Zinc-binding alcohol dehydrogenase domain-containing protein 2;
GN Name=Ptgr3 {ECO:0000303|PubMed:23821743};
GN Synonyms=Zadh2 {ECO:0000312|MGI:MGI:2444835};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Head, and Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=19091015; DOI=10.1186/1471-2105-9-s12-s16;
RA Mizuno Y., Kurochkin I.V., Herberth M., Okazaki Y., Schoenbach C.;
RT "Predicted mouse peroxisome-targeted proteins and their actual subcellular
RT locations.";
RL BMC Bioinformatics 9:S16-S16(2008).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP TISSUE SPECIFICITY, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP INDUCTION, AND FUNCTION.
RX PubMed=23821743; DOI=10.1194/jlr.m037556;
RA Yu Y.H., Chang Y.C., Su T.H., Nong J.Y., Li C.C., Chuang L.M.;
RT "Prostaglandin reductase-3 negatively modulates adipogenesis through
RT regulation of PPARgamma activity.";
RL J. Lipid Res. 54:2391-2399(2013).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-35, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Functions as 15-oxo-prostaglandin 13-reductase and acts on
CC 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha
CC with highest efficiency towards 15-keto-PGE2-alpha. Overexpression
CC represses transcriptional activity of PPARG and inhibits adipocyte
CC differentiation. {ECO:0000269|PubMed:23821743}.
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:23821743};
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:23821743};
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:23821743};
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:23821743};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=55.0 uM for 15-keto-PGE2 {ECO:0000269|PubMed:23821743};
CC KM=75.1 uM for 15-keto-PGE1 {ECO:0000269|PubMed:23821743};
CC KM=42.5 uM for 15-keto-PGF2-alpha {ECO:0000269|PubMed:23821743};
CC KM=53.5 uM for 15-keto-PGF1-alpha {ECO:0000269|PubMed:23821743};
CC Vmax=215.4 nmol/min/mg enzyme with 15-keto-PGE2 as substrate
CC {ECO:0000269|PubMed:23821743};
CC Vmax=109.6 nmol/min/mg enzyme with 15-keto-PGE1 as substrate
CC {ECO:0000269|PubMed:23821743};
CC Vmax=303.3 nmol/min/mg enzyme with 15-keto-PGF2-alpha as substrate
CC {ECO:0000269|PubMed:23821743};
CC Vmax=286.2 nmol/min/mg enzyme with 15-keto-PGF1-alpha as substrate
CC {ECO:0000269|PubMed:23821743};
CC Note=kcat is 8.6 mn(-1) for 15-keto-PGE2, 4.37 mn(-1) for 15-keto-
CC PGE1, 11.55 for mn(-1) for 15-keto-PGF2-alpha, 11.45 mn(-1) for 15-
CC keto-PGF1-alpha. {ECO:0000269|PubMed:23821743};
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:19091015}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:23821743}.
CC -!- INDUCTION: Up-regulated by high fat diet (PubMed:19091015). Down-
CC regulated in white adipose tissue in ob/on mice (PubMed:23821743).
CC {ECO:0000269|PubMed:19091015, ECO:0000269|PubMed:23821743}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Quinone oxidoreductase subfamily. {ECO:0000305}.
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DR EMBL; AK047559; BAC33086.1; -; mRNA.
DR EMBL; AK081988; BAC38389.1; -; mRNA.
DR EMBL; AK083082; BAC38754.1; -; mRNA.
DR CCDS; CCDS29381.1; -.
DR RefSeq; NP_666202.2; NM_146090.5.
DR AlphaFoldDB; Q8BGC4; -.
DR SMR; Q8BGC4; -.
DR BioGRID; 230427; 12.
DR STRING; 10090.ENSMUSP00000052544; -.
DR SwissLipids; SLP:000001624; -.
DR iPTMnet; Q8BGC4; -.
DR PhosphoSitePlus; Q8BGC4; -.
DR SwissPalm; Q8BGC4; -.
DR EPD; Q8BGC4; -.
DR jPOST; Q8BGC4; -.
DR MaxQB; Q8BGC4; -.
DR PaxDb; Q8BGC4; -.
DR PRIDE; Q8BGC4; -.
DR ProteomicsDB; 301871; -.
DR Antibodypedia; 10355; 147 antibodies from 26 providers.
DR DNASU; 225791; -.
DR Ensembl; ENSMUST00000060223; ENSMUSP00000052544; ENSMUSG00000049090.
DR GeneID; 225791; -.
DR KEGG; mmu:225791; -.
DR UCSC; uc008fun.1; mouse.
DR CTD; 225791; -.
DR MGI; MGI:2444835; Zadh2.
DR VEuPathDB; HostDB:ENSMUSG00000049090; -.
DR eggNOG; KOG1196; Eukaryota.
DR GeneTree; ENSGT00920000149172; -.
DR HOGENOM; CLU_026673_3_1_1; -.
DR InParanoid; Q8BGC4; -.
DR OMA; VKPPFDI; -.
DR OrthoDB; 929126at2759; -.
DR PhylomeDB; Q8BGC4; -.
DR TreeFam; TF328691; -.
DR BioGRID-ORCS; 225791; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Zadh2; mouse.
DR PRO; PR:Q8BGC4; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8BGC4; protein.
DR Bgee; ENSMUSG00000049090; Expressed in interventricular septum and 243 other tissues.
DR ExpressionAtlas; Q8BGC4; baseline and differential.
DR Genevisible; Q8BGC4; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0036132; F:13-prostaglandin reductase activity; IMP:UniProtKB.
DR GO; GO:0047522; F:15-oxoprostaglandin 13-oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:UniProtKB.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR002364; Quin_OxRdtase/zeta-crystal_CS.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS01162; QOR_ZETA_CRYSTAL; 1.
PE 1: Evidence at protein level;
KW Acetylation; Lipid metabolism; NADP; Oxidoreductase; Peroxisome;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..377
FT /note="Prostaglandin reductase-3"
FT /id="PRO_0000223466"
FT BINDING 185
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
FT BINDING 205
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
FT BINDING 209
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
FT BINDING 224
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
FT BINDING 247
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
FT BINDING 269
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
FT BINDING 275
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
FT BINDING 303..305
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
FT BINDING 361
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
FT MOD_RES 35
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N4Q0"
SQ SEQUENCE 377 AA; 40529 MW; AA23871FCC081CEE CRC64;
MLRLAAAGAR AIVDMSYARH FLDFQGSAIP RTMQKLVVTR LSPNFHEAVT LRRDCPVPLP
GDGDLLVRNR FVGINASDIN YSAGRYDPSL KPPFDIGFEG IGEVVALGLS ASARYTVGQA
VAYMAPGSFA EYTVVPASIA IPMPSVKPEY LTMLVSGTTA YLSLEELGEL SEGKKVLVTA
AAGGTGQFAV QLSKIAKCHV IGTCSSDEKA AFLKSIGCDR PINYRTEPVE TVLKQEYPEG
VDVVYESVGG AMFDLAVDAL ATKGRLIVIG FISGYQSPTG LSPIKAGVLP TKLLKKSASL
RGFFLNHYFS KYQAAMERLL ELYARGDLVC EVDLGHLAPD GRFIGLESVF QAVDYMYTGK
NTGKLVVELP HPVSSKL
