PTGDS_RAT
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 03-AUG-2022, entry version 176.
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}.
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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 GlyGen; P22057; 2 sites.
DR iPTMnet; P22057; -.
DR PaxDb; P22057; -.
DR PRIDE; P22057; -.
DR Ensembl; ENSRNOT00000020926; ENSRNOP00000020926; ENSRNOG00000015550.
DR GeneID; 25526; -.
DR KEGG; rno:25526; -.
DR UCSC; RGD:3433; rat.
DR CTD; 5730; -.
DR RGD; 3433; Ptgds.
DR eggNOG; ENOG502S6GK; Eukaryota.
DR GeneTree; ENSGT01050000244979; -.
DR HOGENOM; CLU_094061_1_1_1; -.
DR InParanoid; P22057; -.
DR OMA; WFREKKS; -.
DR OrthoDB; 1341030at2759; -.
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 tissues.
DR Genevisible; P22057; RN.
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:0036094; F:small molecule binding; IEA:InterPro.
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 InterPro; IPR002972; PstgldnD_synth.
DR PANTHER; PTHR11430; PTHR11430; 1.
DR PANTHER; PTHR11430:SF86; PTHR11430:SF86; 1.
DR Pfam; PF00061; Lipocalin; 1.
DR SUPFAM; SSF50814; SSF50814; 1.
DR PROSITE; PS00213; LIPOCALIN; 1.
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
