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Protein

Prostaglandin-H2 D-isomerase

Gene

Ptgds

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation. Involved in a variety of CNS functions, such as sedation, NREM sleep and PGE2-induced allodynia, and may have an anti-apoptotic role in oligodendrocytes. Binds small non-substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid and thyroid hormone, and may act as a scavenger for harmful hydrophopic molecules and as a secretory retinoid and thyroid hormone transporter. Possibly involved in development and maintenance of the blood-brain, blood-retina, blood-aqueous humor and blood-testis barrier. It is likely to play important roles in both maturation and maintenance of the central nervous system and male reproductive system.4 Publications

Catalytic activityi

(5Z,13E,15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E,15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei65 – 651Nucleophile1 Publication

GO - Molecular functioni

  • fatty acid binding Source: Ensembl
  • prostaglandin-D synthase activity Source: UniProtKB
  • retinoid binding Source: UniProtKB
  • transporter activity Source: UniProtKB

GO - Biological processi

  • negative regulation of male germ cell proliferation Source: Ensembl
  • prostaglandin biosynthetic process Source: UniProtKB
  • regulation of circadian sleep/wake cycle, sleep Source: UniProtKB
  • response to glucocorticoid Source: RGD
  • transport Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Isomerase

Keywords - Biological processi

Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism, Transport

Enzyme and pathway databases

BRENDAi5.3.99.2. 5301.
ReactomeiREACT_320384. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).

Names & Taxonomyi

Protein namesi
Recommended name:
Prostaglandin-H2 D-isomerase (EC:5.3.99.2)
Alternative name(s):
Glutathione-independent PGD synthase
Lipocalin-type prostaglandin-D synthase
Prostaglandin-D2 synthase
Short name:
PGD2 synthase
Short name:
PGDS
Short name:
PGDS2
Gene namesi
Name:Ptgds
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi3433. Ptgds.

Subcellular locationi

  • Rough endoplasmic reticulum
  • Nucleus membrane
  • Golgi apparatus
  • Cytoplasmperinuclear region
  • Secreted

  • Note: Detected on rough endoplasmic reticulum of arachnoid and menigioma cells. Localized to the nuclear envelope, Golgi apparatus, secretory vesicles and spherical cytoplasmic structures in arachnoid trabecular cells, and to circular cytoplasmic structures in meningeal macrophages and perivascular microglial cells. In oligodendrocytes, localized to the rough endoplasmic reticulum and nuclear envelope. In retinal pigment epithelial cells, localized to distinct cytoplasmic domains including the perinuclear region. Also secreted.

GO - Cellular componenti

  • extracellular exosome Source: Ensembl
  • extracellular region Source: UniProtKB
  • extracellular space Source: RGD
  • Golgi apparatus Source: UniProtKB
  • nuclear envelope Source: UniProtKB
  • nuclear membrane Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • rough endoplasmic reticulum Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane, Nucleus, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi65 – 651C → A or S: Loss of enzymatic activity. 1 Publication
Mutagenesisi89 – 891C → A or S: Disrupts disulfide bond. 1 Publication
Mutagenesisi186 – 1861C → A or S: Disrupts disulfide bond. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Add
BLAST
Chaini25 – 189165Prostaglandin-H2 D-isomerasePRO_0000017950Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei25 – 251Pyrrolidone carboxylic acid1 Publication
Glycosylationi51 – 511N-linked (GlcNAc...)1 Publication
Glycosylationi78 – 781N-linked (GlcNAc...)1 Publication
Disulfide bondi89 ↔ 1861 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Pyrrolidone carboxylic acid

Proteomic databases

PaxDbiP22057.
PRIDEiP22057.

Expressioni

Tissue specificityi

Abundant in the brain and CNS, where it is expressed in tissues of the blood-brain barrier and secreted into the cerebro-spinal fluid. In the eye, it is expressed in the pigmented epithelium of the retina and the nonpigmented epithelium of the iris and ciliary body, and accumulates within the interphotoreceptor matrix, photoreceptors, and aqueous and vitreous humors. In the male reproductive system, it is expressed in the testis and epididymis, and is secreted into the seminal fluid. It has also been detected in the cochlea.9 Publications

Developmental stagei

In the brain it is localized in many neurons at 1-2 weeks after birth, whereas in mature animals it is localized to tissues of the blood-brain barrier.1 Publication

Inductioni

By IL-1 beta and thyroid hormone. Probably induced by dexamethasone, dihydrotestosterone, progesterone, retinoic acid and retinal. Repressed by the Notch-Hes signaling pathway.4 Publications

Gene expression databases

GenevisibleiP22057. RN.

Interactioni

Subunit structurei

Monomer.By similarity

Protein-protein interaction databases

BioGridi247558. 2 interactions.
STRINGi10116.ENSRNOP00000020926.

Structurei

3D structure databases

ProteinModelPortaliP22057.
SMRiP22057. Positions 24-189.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.By similarity

Sequence similaritiesi

Belongs to the calycin superfamily. Lipocalin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG45731.
GeneTreeiENSGT00620000088005.
HOGENOMiHOG000231660.
HOVERGENiHBG106490.
InParanoidiP22057.
KOiK01830.
OMAiKGPGQDF.
OrthoDBiEOG78PVBH.
PhylomeDBiP22057.
TreeFamiTF336103.

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
InterProiIPR012674. Calycin.
IPR011038. Calycin-like.
IPR002345. Lipocalin.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
IPR002972. PstgldnD_synth.
[Graphical view]
PfamiPF00061. Lipocalin. 1 hit.
[Graphical view]
PRINTSiPR00179. LIPOCALIN.
PR01254. PGNDSYNTHASE.
SUPFAMiSSF50814. SSF50814. 1 hit.
PROSITEiPS00213. LIPOCALIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P22057-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAALPMLWTG LVLLGLLGFP QTPAQGHDTV QPNFQQDKFL GRWYSAGLAS
60 70 80 90 100
NSSWFREKKE LLFMCQTVVA PSTEGGLNLT STFLRKNQCE TKVMVLQPAG
110 120 130 140 150
VPGQYTYNSP HWGSFHSLSV VETDYDEYAF LFSKGTKGPG QDFRMATLYS
160 170 180
RAQLLKEELK EKFITFSKDQ GLTEEDIVFL PQPDKCIQE
Length:189
Mass (Da):21,301
Last modified:February 1, 1996 - v2
Checksum:i866E4CFE0F814FDC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti138 – 1381G → A in S66190 (PubMed:8216319).Curated
Sequence conflicti144 – 1441R → G in S66190 (PubMed:8216319).Curated

Mass spectrometryi

Molecular mass is 18808 Da from positions 25 - 189. Determined by MALDI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04488 mRNA. Translation: AAA41839.1.
M94134 Genomic DNA. Translation: AAA41840.1.
S66190 mRNA. No translation available.
PIRiA32202.
S65717.
RefSeqiNP_037147.1. NM_013015.2.
UniGeneiRn.11400.

Genome annotation databases

EnsembliENSRNOT00000020926; ENSRNOP00000020926; ENSRNOG00000015550.
GeneIDi25526.
KEGGirno:25526.
UCSCiRGD:3433. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04488 mRNA. Translation: AAA41839.1.
M94134 Genomic DNA. Translation: AAA41840.1.
S66190 mRNA. No translation available.
PIRiA32202.
S65717.
RefSeqiNP_037147.1. NM_013015.2.
UniGeneiRn.11400.

3D structure databases

ProteinModelPortaliP22057.
SMRiP22057. Positions 24-189.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247558. 2 interactions.
STRINGi10116.ENSRNOP00000020926.

Proteomic databases

PaxDbiP22057.
PRIDEiP22057.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000020926; ENSRNOP00000020926; ENSRNOG00000015550.
GeneIDi25526.
KEGGirno:25526.
UCSCiRGD:3433. rat.

Organism-specific databases

CTDi5730.
RGDi3433. Ptgds.

Phylogenomic databases

eggNOGiNOG45731.
GeneTreeiENSGT00620000088005.
HOGENOMiHOG000231660.
HOVERGENiHBG106490.
InParanoidiP22057.
KOiK01830.
OMAiKGPGQDF.
OrthoDBiEOG78PVBH.
PhylomeDBiP22057.
TreeFamiTF336103.

Enzyme and pathway databases

BRENDAi5.3.99.2. 5301.
ReactomeiREACT_320384. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).

Miscellaneous databases

NextBioi607007.
PROiP22057.

Gene expression databases

GenevisibleiP22057. RN.

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
InterProiIPR012674. Calycin.
IPR011038. Calycin-like.
IPR002345. Lipocalin.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
IPR002972. PstgldnD_synth.
[Graphical view]
PfamiPF00061. Lipocalin. 1 hit.
[Graphical view]
PRINTSiPR00179. LIPOCALIN.
PR01254. PGNDSYNTHASE.
SUPFAMiSSF50814. SSF50814. 1 hit.
PROSITEiPS00213. LIPOCALIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Primary structure of rat brain prostaglandin D synthetase deduced from cDNA sequence."
    Urade Y., Nagata A., Suzuki Y., Fujii Y., Hayaishi O.
    J. Biol. Chem. 264:1041-1045(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 39-53; 60-85; 93-108 AND 138-185, TISSUE SPECIFICITY, GLYCOSYLATION.
    Tissue: Brain.
  2. "Structural organization of the gene for prostaglandin D synthase in the rat brain."
    Igarashi M., Nagata A., Toh H., Urade Y., Hayaihi O.
    Proc. Natl. Acad. Sci. U.S.A. 89:5376-5380(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: Wistar.
  3. "Proteins of rat serum, urine, and cerebrospinal fluid: VI. Further protein identifications and interstrain comparison."
    Wait R., Gianazza E., Eberini I., Sironi L., Dunn M.J., Gemeiner M., Miller I.
    Electrophoresis 22:3043-3052(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 26-42, PYROGLUTAMATE FORMATION AT GLN-25, TISSUE SPECIFICITY, MASS SPECTROMETRY.
    Strain: Wistar Kyoto.
    Tissue: Cerebrospinal fluid.
  4. "Astrocytes synthesize and secrete prostaglandin D synthetase in vitro."
    Giacomelli S., Leone M.-G., Grima J., Silvestrini B., Cheng C.Y.
    Biochim. Biophys. Acta 1310:269-276(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 27-41, TISSUE SPECIFICITY.
    Tissue: Cerebrospinal fluid.
  5. "Structural and functional significance of cysteine residues of glutathione-independent prostaglandin D synthase. Identification of Cys65 as an essential thiol."
    Urade Y., Tanaka T., Eguchi N., Kikuchi M., Kimura H., Toh H., Hayaishi O.
    J. Biol. Chem. 270:1422-1428(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 26-32, ACTIVE SITE, DISULFIDE BOND, MUTAGENESIS OF CYS-65; CYS-89 AND CYS-186.
    Tissue: Brain.
  6. "Brain-specific prostaglandin D2 synthetase mRNA is dependent on thyroid hormone during rat brain development."
    Garcia-Fernandez L.F., Iniguez M.A., Rodriguez-Pena A., Munoz A., Bernal J.
    Biochem. Biophys. Res. Commun. 196:396-401(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE OF 124-189.
  7. Lubec G., Kang S.U., Lubec S.
    Submitted (SEP-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 169-185, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  8. "Lipocalin-type prostaglandin D synthase (beta-trace) is a newly recognized type of retinoid transporter."
    Tanaka T., Urade Y., Kimura H., Eguchi N., Nishikawa A., Hayaishi O.
    J. Biol. Chem. 272:15789-15795(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION BY RETINOIDS.
  9. "Binding of biliverdin, bilirubin, and thyroid hormones to lipocalin-type prostaglandin D synthase."
    Beuckmann C.T., Aoyagi M., Okazaki I., Hiroike T., Toh H., Hayaishi O., Urade Y.
    Biochemistry 38:8006-8013(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION.
  10. "Cellular localization of lipocalin-type prostaglandin D synthase (beta-trace) in the central nervous system of the adult rat."
    Beuckmann C.T., Lazarus M., Gerashchenko D., Mizoguchi A., Nomura S., Mohri I., Uesugi A., Kaneko T., Mizuno N., Hayaishi O., Urade Y.
    J. Comp. Neurol. 428:62-78(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  11. "Sertoli cell prostaglandin D2 synthetase is a multifunctional molecule: its expression and regulation."
    Samy E.T., Li J.C.H., Grima J., Lee W.M., Silvestrini B., Cheng C.Y.
    Endocrinology 141:710-721(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION BY PROGESTERONE, RETINOIDS AND THYROID HORMONE.
  12. "Lipocalin-type prostaglandin D synthase (beta-trace) is located in pigment epithelial cells of rat retina and accumulates within interphotoreceptor matrix."
    Beuckmann C.T., Gordon W.C., Kanaoka Y., Eguchi N., Marcheselli V.L., Gerashchenko D.Y., Urade Y., Hayaishi O., Bazan N.G.
    J. Neurosci. 16:6119-6124(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  13. "Dominant expression of mRNA for prostaglandin D synthase in leptomeninges, choroid plexus, and oligodendrocytes of the adult rat brain."
    Urade Y., Kitahama K., Ohishi H., Kaneko T., Mizuno N., Hayaishi O.
    Proc. Natl. Acad. Sci. U.S.A. 90:9070-9074(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  14. "Localization of lipocalin-type prostaglandin D synthase (beta-trace) in iris, ciliary body, and eye fluids."
    Gerashchenko D.Y., Beuckmann C.T., Marcheselli V.L., Gordon W.C., Kanaoka Y., Eguchi N., Urade Y., Hayaishi O., Bazan N.G.
    Invest. Ophthalmol. Vis. Sci. 39:198-203(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  15. "Rat prostaglandin D2 synthetase: its tissue distribution, changes during maturation, and regulation in the testis and epididymis."
    Sorrentino C., Silvestrini B., Braghiroli L., Chung S.S.W., Giacomelli S., Leone M.-G., Xie Y.-B., Sui Y.-P., Mo M.-Y., Cheng C.Y.
    Biol. Reprod. 59:843-853(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION BY DIHYDROTESTOSTERONE.
  16. "Identification of a thyroid hormone response element in the promoter region of the rat lipocalin-type prostaglandin D synthase (beta-trace) gene."
    Garcia-Fernandez L.F., Urade Y., Hayaishi O., Bernal J., Munoz A.
    Brain Res. Mol. Brain Res. 55:321-330(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY THYROID HORMONE AND RETINOIDS.
  17. "Regulation of lipocalin-type prostaglandin D synthase gene expression by Hes-1 through E-box and interleukin-1 beta via two NF-kappaB elements in rat leptomeningeal cells."
    Fujimori K., Fujitani Y., Kadoyama K., Kumanogoh H., Ishikawa K., Urade Y.
    J. Biol. Chem. 278:6018-6026(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY IL-1 BETA, REPRESSION BY NOTCH-HES.
  18. "The first lipocalin with enzymatic activity."
    Peitsch M.C., Boguski M.S.
    Trends Biochem. Sci. 16:363-363(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: SIMILARITY TO THE LIPOCALIN FAMILY.

Entry informationi

Entry nameiPTGDS_RAT
AccessioniPrimary (citable) accession number: P22057
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: February 1, 1996
Last modified: July 22, 2015
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.