ID PTGDS_RAT Reviewed; 189 AA. AC P22057; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 2. DT 24-JAN-2024, entry version 183. DE RecName: Full=Prostaglandin-H2 D-isomerase; DE EC=5.3.99.2 {ECO:0000269|PubMed:10387044}; DE AltName: Full=Glutathione-independent PGD synthase; DE AltName: Full=Lipocalin-type prostaglandin-D synthase; DE AltName: Full=Prostaglandin-D2 synthase; DE Short=PGD2 synthase; DE Short=PGDS; DE Short=PGDS2; DE Flags: Precursor; GN Name=Ptgds; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 39-53; 60-85; 93-108 AND RP 138-185, TISSUE SPECIFICITY, AND GLYCOSYLATION. RC TISSUE=Brain; RX PubMed=2642896; DOI=10.1016/s0021-9258(19)85050-0; RA Urade Y., Nagata A., Suzuki Y., Fujii Y., Hayaishi O.; RT "Primary structure of rat brain prostaglandin D synthetase deduced from RT cDNA sequence."; RL J. Biol. Chem. 264:1041-1045(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Wistar; RX PubMed=1608945; DOI=10.1073/pnas.89.12.5376; RA Igarashi M., Nagata A., Toh H., Urade Y., Hayaihi O.; RT "Structural organization of the gene for prostaglandin D synthase in the RT rat brain."; RL Proc. Natl. Acad. Sci. U.S.A. 89:5376-5380(1992). RN [3] RP PROTEIN SEQUENCE OF 26-42, PYROGLUTAMATE FORMATION AT GLN-25, TISSUE RP SPECIFICITY, AND MASS SPECTROMETRY. RC STRAIN=Wistar Kyoto; TISSUE=Cerebrospinal fluid; RX PubMed=11565799; RX DOI=10.1002/1522-2683(200108)22:14<3043::aid-elps3043>3.0.co;2-m; RA Wait R., Gianazza E., Eberini I., Sironi L., Dunn M.J., Gemeiner M., RA Miller I.; RT "Proteins of rat serum, urine, and cerebrospinal fluid: VI. Further protein RT identifications and interstrain comparison."; RL Electrophoresis 22:3043-3052(2001). RN [4] RP PROTEIN SEQUENCE OF 27-41, AND TISSUE SPECIFICITY. RC TISSUE=Cerebrospinal fluid; RX PubMed=8599604; DOI=10.1016/0167-4889(95)00182-4; RA Giacomelli S., Leone M.-G., Grima J., Silvestrini B., Cheng C.Y.; RT "Astrocytes synthesize and secrete prostaglandin D synthetase in vitro."; RL Biochim. Biophys. Acta 1310:269-276(1996). RN [5] RP PROTEIN SEQUENCE OF 26-32, ACTIVE SITE, DISULFIDE BOND, AND MUTAGENESIS OF RP CYS-65; CYS-89 AND CYS-186. RC TISSUE=Brain; RX PubMed=7836410; DOI=10.1074/jbc.270.3.1422; RA Urade Y., Tanaka T., Eguchi N., Kikuchi M., Kimura H., Toh H., Hayaishi O.; RT "Structural and functional significance of cysteine residues of RT glutathione-independent prostaglandin D synthase. Identification of Cys65 RT as an essential thiol."; RL J. Biol. Chem. 270:1422-1428(1995). RN [6] RP NUCLEOTIDE SEQUENCE OF 124-189. RX PubMed=8216319; DOI=10.1006/bbrc.1993.2262; RA Garcia-Fernandez L.F., Iniguez M.A., Rodriguez-Pena A., Munoz A., RA Bernal J.; RT "Brain-specific prostaglandin D2 synthetase mRNA is dependent on thyroid RT hormone during rat brain development."; RL Biochem. Biophys. Res. Commun. 196:396-401(1993). RN [7] RP PROTEIN SEQUENCE OF 169-185, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Brain; RA Lubec G., Kang S.U., Lubec S.; RL Submitted (SEP-2007) to UniProtKB. RN [8] RP FUNCTION, AND ACTIVITY REGULATION BY RETINOIDS. RX PubMed=9188476; DOI=10.1074/jbc.272.25.15789; RA Tanaka T., Urade Y., Kimura H., Eguchi N., Nishikawa A., Hayaishi O.; RT "Lipocalin-type prostaglandin D synthase (beta-trace) is a newly recognized RT type of retinoid transporter."; RL J. Biol. Chem. 272:15789-15795(1997). RN [9] RP FUNCTION, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY. RX PubMed=10387044; DOI=10.1021/bi990261p; RA Beuckmann C.T., Aoyagi M., Okazaki I., Hiroike T., Toh H., Hayaishi O., RA Urade Y.; RT "Binding of biliverdin, bilirubin, and thyroid hormones to lipocalin-type RT prostaglandin D synthase."; RL Biochemistry 38:8006-8013(1999). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11058225; RX DOI=10.1002/1096-9861(20001204)428:1<62::aid-cne6>3.0.co;2-e; RA Beuckmann C.T., Lazarus M., Gerashchenko D., Mizoguchi A., Nomura S., RA Mohri I., Uesugi A., Kaneko T., Mizuno N., Hayaishi O., Urade Y.; RT "Cellular localization of lipocalin-type prostaglandin D synthase (beta- RT trace) in the central nervous system of the adult rat."; RL J. Comp. Neurol. 428:62-78(2000). RN [11] RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY PROGESTERONE, AND RETINOIDS AND RP THYROID HORMONE. RX PubMed=10650953; DOI=10.1210/endo.141.2.7329; RA Samy E.T., Li J.C.H., Grima J., Lee W.M., Silvestrini B., Cheng C.Y.; RT "Sertoli cell prostaglandin D2 synthetase is a multifunctional molecule: RT its expression and regulation."; RL Endocrinology 141:710-721(2000). RN [12] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=8815894; DOI=10.1523/jneurosci.16-19-06119.1996; RA Beuckmann C.T., Gordon W.C., Kanaoka Y., Eguchi N., Marcheselli V.L., RA Gerashchenko D.Y., Urade Y., Hayaishi O., Bazan N.G.; RT "Lipocalin-type prostaglandin D synthase (beta-trace) is located in pigment RT epithelial cells of rat retina and accumulates within interphotoreceptor RT matrix."; RL J. Neurosci. 16:6119-6124(1996). RN [13] RP TISSUE SPECIFICITY. RX PubMed=8415655; DOI=10.1073/pnas.90.19.9070; RA Urade Y., Kitahama K., Ohishi H., Kaneko T., Mizuno N., Hayaishi O.; RT "Dominant expression of mRNA for prostaglandin D synthase in leptomeninges, RT choroid plexus, and oligodendrocytes of the adult rat brain."; RL Proc. Natl. Acad. Sci. U.S.A. 90:9070-9074(1993). RN [14] RP TISSUE SPECIFICITY. RX PubMed=9430563; RA Gerashchenko D.Y., Beuckmann C.T., Marcheselli V.L., Gordon W.C., RA Kanaoka Y., Eguchi N., Urade Y., Hayaishi O., Bazan N.G.; RT "Localization of lipocalin-type prostaglandin D synthase (beta-trace) in RT iris, ciliary body, and eye fluids."; RL Invest. Ophthalmol. Vis. Sci. 39:198-203(1998). RN [15] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION BY RP DIHYDROTESTOSTERONE. RX PubMed=9746734; DOI=10.1095/biolreprod59.4.843; RA Sorrentino C., Silvestrini B., Braghiroli L., Chung S.S.W., Giacomelli S., RA Leone M.-G., Xie Y.-B., Sui Y.-P., Mo M.-Y., Cheng C.Y.; RT "Rat prostaglandin D2 synthetase: its tissue distribution, changes during RT maturation, and regulation in the testis and epididymis."; RL Biol. Reprod. 59:843-853(1998). RN [16] RP INDUCTION BY THYROID HORMONE AND RETINOIDS. RX PubMed=9582446; DOI=10.1016/s0169-328x(98)00015-1; RA Garcia-Fernandez L.F., Urade Y., Hayaishi O., Bernal J., Munoz A.; RT "Identification of a thyroid hormone response element in the promoter RT region of the rat lipocalin-type prostaglandin D synthase (beta-trace) RT gene."; RL Brain Res. Mol. Brain Res. 55:321-330(1998). RN [17] RP INDUCTION BY IL-1 BETA, AND REPRESSION BY NOTCH-HES. RX PubMed=12488457; DOI=10.1074/jbc.m208288200; RA Fujimori K., Fujitani Y., Kadoyama K., Kumanogoh H., Ishikawa K., Urade Y.; RT "Regulation of lipocalin-type prostaglandin D synthase gene expression by RT Hes-1 through E-box and interleukin-1 beta via two NF-kappaB elements in RT rat leptomeningeal cells."; RL J. Biol. Chem. 278:6018-6026(2003). RN [18] RP SIMILARITY TO THE LIPOCALIN FAMILY. RX PubMed=1723819; DOI=10.1016/0968-0004(91)90149-p; RA Peitsch M.C., Boguski M.S.; RT "The first lipocalin with enzymatic activity."; RL Trends Biochem. Sci. 16:363-363(1991). CC -!- FUNCTION: Catalyzes the conversion of PGH2 to PGD2, a prostaglandin CC involved in smooth muscle contraction/relaxation and a potent inhibitor CC of platelet aggregation. Involved in a variety of CNS functions, such CC as sedation, NREM sleep and PGE2-induced allodynia, and may have an CC anti-apoptotic role in oligodendrocytes. Binds small non-substrate CC lipophilic molecules, including biliverdin, bilirubin, retinal, CC retinoic acid and thyroid hormone, and may act as a scavenger for CC harmful hydrophobic molecules and as a secretory retinoid and thyroid CC hormone transporter. Possibly involved in development and maintenance CC of the blood-brain, blood-retina, blood-aqueous humor and blood-testis CC barrier. It is likely to play important roles in both maturation and CC maintenance of the central nervous system and male reproductive system CC (PubMed:10387044, PubMed:10650953, PubMed:11058225, PubMed:9188476). CC Involved in PLA2G3-dependent maturation of mast cells. PLA2G3 is CC secreted by immature mast cells and acts on nearby fibroblasts upstream CC to PTDGS to synthesize PGD2, which in turn promotes mast cell CC maturation and degranulation via PTGDR (By similarity). CC {ECO:0000250|UniProtKB:O09114, ECO:0000269|PubMed:10387044, CC ECO:0000269|PubMed:10650953, ECO:0000269|PubMed:11058225, CC ECO:0000269|PubMed:9188476}. CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin H2 = prostaglandin D2; Xref=Rhea:RHEA:10600, CC ChEBI:CHEBI:57405, ChEBI:CHEBI:57406; EC=5.3.99.2; CC Evidence={ECO:0000269|PubMed:10387044}; CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P41222}. CC -!- SUBCELLULAR LOCATION: Rough endoplasmic reticulum CC {ECO:0000250|UniProtKB:P41222}. Nucleus membrane CC {ECO:0000250|UniProtKB:P41222}. Golgi apparatus CC {ECO:0000250|UniProtKB:P41222}. Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:P41222}. Secreted CC {ECO:0000250|UniProtKB:P41222}. Note=Detected on rough endoplasmic CC reticulum of arachnoid and menigioma cells. Localized to the nuclear CC envelope, Golgi apparatus, secretory vesicles and spherical cytoplasmic CC structures in arachnoid trabecular cells, and to circular cytoplasmic CC structures in meningeal macrophages and perivascular microglial cells. CC In oligodendrocytes, localized to the rough endoplasmic reticulum and CC nuclear envelope. In retinal pigment epithelial cells, localized to CC distinct cytoplasmic domains including the perinuclear region. Also CC secreted. {ECO:0000250|UniProtKB:P41222}. CC -!- TISSUE SPECIFICITY: Abundant in the brain and CNS, where it is CC expressed in tissues of the blood-brain barrier and secreted into the CC cerebro-spinal fluid. In the eye, it is expressed in the pigmented CC epithelium of the retina and the nonpigmented epithelium of the iris CC and ciliary body, and accumulates within the interphotoreceptor matrix, CC photoreceptors, and aqueous and vitreous humors. In the male CC reproductive system, it is expressed in the testis and epididymis, and CC is secreted into the seminal fluid. It has also been detected in the CC cochlea. {ECO:0000269|PubMed:10650953, ECO:0000269|PubMed:11058225, CC ECO:0000269|PubMed:11565799, ECO:0000269|PubMed:2642896, CC ECO:0000269|PubMed:8415655, ECO:0000269|PubMed:8599604, CC ECO:0000269|PubMed:8815894, ECO:0000269|PubMed:9430563, CC ECO:0000269|PubMed:9746734}. CC -!- DEVELOPMENTAL STAGE: In the brain it is localized in many neurons at 1- CC 2 weeks after birth, whereas in mature animals it is localized to CC tissues of the blood-brain barrier. {ECO:0000269|PubMed:9746734}. CC -!- INDUCTION: By IL-1 beta and thyroid hormone. Probably induced by CC dexamethasone, dihydrotestosterone, progesterone, retinoic acid and CC retinal. Repressed by the Notch-Hes signaling pathway. CC {ECO:0000269|PubMed:10650953, ECO:0000269|PubMed:12488457, CC ECO:0000269|PubMed:9582446, ECO:0000269|PubMed:9746734}. CC -!- DOMAIN: Forms a beta-barrel structure that accommodates hydrophobic CC ligands in its interior. {ECO:0000250|UniProtKB:P41222}. CC -!- MASS SPECTROMETRY: Mass=18808; Method=MALDI; CC Evidence={ECO:0000269|PubMed:11565799}; CC -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J04488; AAA41839.1; -; mRNA. DR EMBL; M94134; AAA41840.1; -; Genomic_DNA. DR EMBL; S66190; -; NOT_ANNOTATED_CDS; mRNA. DR PIR; A32202; A32202. DR PIR; S65717; S65717. DR RefSeq; NP_037147.1; NM_013015.2. DR AlphaFoldDB; P22057; -. DR BMRB; P22057; -. DR SMR; P22057; -. DR BioGRID; 247558; 2. DR STRING; 10116.ENSRNOP00000020926; -. DR GlyCosmos; P22057; 2 sites, No reported glycans. DR GlyGen; P22057; 2 sites. DR iPTMnet; P22057; -. DR PhosphoSitePlus; P22057; -. DR PaxDb; 10116-ENSRNOP00000020926; -. DR Ensembl; ENSRNOT00000020926.6; ENSRNOP00000020926.4; ENSRNOG00000015550.6. DR Ensembl; ENSRNOT00055000890; ENSRNOP00055000704; ENSRNOG00055000514. DR Ensembl; ENSRNOT00060045439; ENSRNOP00060037730; ENSRNOG00060026230. DR Ensembl; ENSRNOT00065044097; ENSRNOP00065036179; ENSRNOG00065025596. DR GeneID; 25526; -. DR KEGG; rno:25526; -. DR UCSC; RGD:3433; rat. DR AGR; RGD:3433; -. DR CTD; 5730; -. DR RGD; 3433; Ptgds. DR eggNOG; ENOG502S6GK; Eukaryota. DR GeneTree; ENSGT01100000263580; -. DR HOGENOM; CLU_094061_1_1_1; -. DR InParanoid; P22057; -. DR OMA; LPKTDQC; -. DR OrthoDB; 5266874at2759; -. DR PhylomeDB; P22057; -. DR TreeFam; TF336103; -. DR BRENDA; 5.3.99.2; 5301. DR Reactome; R-RNO-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX). DR SABIO-RK; P22057; -. DR PRO; PR:P22057; -. DR Proteomes; UP000002494; Chromosome 3. DR Bgee; ENSRNOG00000015550; Expressed in cerebellum and 18 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:RGD. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0005635; C:nuclear envelope; NAS:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005791; C:rough endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005504; F:fatty acid binding; ISO:RGD. DR GO; GO:0004667; F:prostaglandin-D synthase activity; IDA:UniProtKB. DR GO; GO:0005501; F:retinoid binding; IDA:UniProtKB. DR GO; GO:0010467; P:gene expression; ISO:RGD. DR GO; GO:0043303; P:mast cell degranulation; IEA:UniProtKB-KW. DR GO; GO:2000255; P:negative regulation of male germ cell proliferation; ISO:RGD. DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB. DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; ISS:UniProtKB. DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD. DR Gene3D; 2.40.128.20; -; 1. DR InterPro; IPR012674; Calycin. DR InterPro; IPR002345; Lipocalin. DR InterPro; IPR022272; Lipocalin_CS. DR InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom. DR PANTHER; PTHR11430; LIPOCALIN; 1. DR PANTHER; PTHR11430:SF86; PROSTAGLANDIN-H2 D-ISOMERASE; 1. DR Pfam; PF00061; Lipocalin; 1. DR PRINTS; PR00179; LIPOCALIN. DR PRINTS; PR01254; PGNDSYNTHASE. DR SUPFAM; SSF50814; Lipocalins; 1. DR PROSITE; PS00213; LIPOCALIN; 1. DR Genevisible; P22057; RN. PE 1: Evidence at protein level; KW Cytoplasm; Direct protein sequencing; Disulfide bond; KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism; KW Glycoprotein; Golgi apparatus; Isomerase; Lipid biosynthesis; KW Lipid metabolism; Mast cell degranulation; Membrane; Nucleus; KW Prostaglandin biosynthesis; Prostaglandin metabolism; KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal; KW Transport. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:7836410" FT CHAIN 25..189 FT /note="Prostaglandin-H2 D-isomerase" FT /id="PRO_0000017950" FT ACT_SITE 65 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:7836410" FT MOD_RES 25 FT /note="Pyrrolidone carboxylic acid" FT /evidence="ECO:0000269|PubMed:11565799" FT CARBOHYD 51 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:2642896" FT CARBOHYD 78 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:2642896" FT DISULFID 89..186 FT /evidence="ECO:0000269|PubMed:7836410" FT MUTAGEN 65 FT /note="C->A,S: Loss of enzymatic activity." FT /evidence="ECO:0000269|PubMed:7836410" FT MUTAGEN 89 FT /note="C->A,S: Disrupts disulfide bond." FT /evidence="ECO:0000269|PubMed:7836410" FT MUTAGEN 186 FT /note="C->A,S: Disrupts disulfide bond." FT /evidence="ECO:0000269|PubMed:7836410" FT CONFLICT 138 FT /note="G -> A (in Ref. 6; S66190)" FT /evidence="ECO:0000305" FT CONFLICT 144 FT /note="R -> G (in Ref. 6; S66190)" FT /evidence="ECO:0000305" SQ SEQUENCE 189 AA; 21301 MW; 866E4CFE0F814FDC CRC64; MAALPMLWTG LVLLGLLGFP QTPAQGHDTV QPNFQQDKFL GRWYSAGLAS NSSWFREKKE LLFMCQTVVA PSTEGGLNLT STFLRKNQCE TKVMVLQPAG VPGQYTYNSP HWGSFHSLSV VETDYDEYAF LFSKGTKGPG QDFRMATLYS RAQLLKEELK EKFITFSKDQ GLTEEDIVFL PQPDKCIQE //