Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P22057 (PTGDS_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Ptgds
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length189 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9 Ref.10 Ref.11

Catalytic activity

(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.

Subunit structure

Monomer By similarity.

Subcellular location

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. Ref.10 Ref.12

Tissue specificity

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. Ref.1 Ref.3 Ref.4 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15

Developmental stage

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. Ref.15

Induction

By IL-1 beta and thyroid hormone. Probably induced by dexamethasone, dihydrotestosterone, progesterone, retinoic acid and retinal. Repressed by the Notch-Hes signaling pathway. Ref.8 Ref.9 Ref.11 Ref.15 Ref.16 Ref.17

Domain

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

Sequence similarities

Belongs to the calycin superfamily. Lipocalin family.

Mass spectrometry

Molecular mass is 18808 Da from positions 25 - 189. Determined by MALDI. Ref.3

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
Prostaglandin biosynthesis
Prostaglandin metabolism
Transport
   Cellular componentCytoplasm
Endoplasmic reticulum
Golgi apparatus
Membrane
Nucleus
Secreted
   DomainSignal
   Molecular functionIsomerase
   PTMDisulfide bond
Glycoprotein
Pyrrolidone carboxylic acid
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processprostaglandin biosynthetic process

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of circadian sleep/wake cycle, sleep

Inferred from sequence or structural similarity PubMed 10781097. Source: UniProtKB

response to glucocorticoid

Inferred from expression pattern PubMed 14618091. Source: RGD

transport

Inferred from direct assay Ref.9. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.10. Source: UniProtKB

extracellular region

Inferred from direct assay Ref.12. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 17259069. Source: RGD

nuclear envelope

Non-traceable author statement Ref.10. Source: UniProtKB

nuclear membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

rough endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionfatty acid binding

Inferred from electronic annotation. Source: Ensembl

prostaglandin-D synthase activity

Inferred from direct assay Ref.5. Source: UniProtKB

retinoid binding

Inferred from direct assay Ref.8. Source: UniProtKB

transporter activity

Inferred from direct assay Ref.9. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Chain25 – 189165Prostaglandin-H2 D-isomerase
PRO_0000017950

Sites

Active site651Nucleophile Ref.5

Amino acid modifications

Modified residue251Pyrrolidone carboxylic acid
Glycosylation511N-linked (GlcNAc...)
Glycosylation781N-linked (GlcNAc...)
Disulfide bond89 ↔ 186 Ref.5

Experimental info

Mutagenesis651C → A or S: Loss of enzymatic activity. Ref.5
Mutagenesis891C → A or S: Disrupts disulfide bond. Ref.5
Mutagenesis1861C → A or S: Disrupts disulfide bond. Ref.5
Sequence conflict1381G → A in S66190. Ref.6
Sequence conflict1441R → G in S66190. Ref.6

Sequences

Sequence LengthMass (Da)Tools
P22057 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: 866E4CFE0F814FDC

FASTA18921,301
        10         20         30         40         50         60 
MAALPMLWTG LVLLGLLGFP QTPAQGHDTV QPNFQQDKFL GRWYSAGLAS NSSWFREKKE 

        70         80         90        100        110        120 
LLFMCQTVVA PSTEGGLNLT STFLRKNQCE TKVMVLQPAG VPGQYTYNSP HWGSFHSLSV 

       130        140        150        160        170        180 
VETDYDEYAF LFSKGTKGPG QDFRMATLYS RAQLLKEELK EKFITFSKDQ GLTEEDIVFL 


PQPDKCIQE 

« Hide

References

[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, 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, COFACTOR, 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04488 mRNA. Translation: AAA41839.1.
M94134 Genomic DNA. Translation: AAA41840.1.
S66190 mRNA. No translation available.
PIRA32202.
S65717.
RefSeqNP_037147.1. NM_013015.2.
UniGeneRn.11400.

3D structure databases

ProteinModelPortalP22057.
SMRP22057. Positions 24-189.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247558. 2 interactions.
STRING10116.ENSRNOP00000020926.

Proteomic databases

PaxDbP22057.
PRIDEP22057.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000020926; ENSRNOP00000020926; ENSRNOG00000015550.
GeneID25526.
KEGGrno:25526.
UCSCRGD:3433. rat.

Organism-specific databases

CTD5730.
RGD3433. Ptgds.

Phylogenomic databases

eggNOGNOG45731.
GeneTreeENSGT00620000088005.
HOGENOMHOG000231660.
HOVERGENHBG106490.
KOK01830.
OMAPGQDFRM.
OrthoDBEOG78PVBH.
PhylomeDBP22057.
TreeFamTF336103.

Gene expression databases

GenevestigatorP22057.

Family and domain databases

Gene3D2.40.128.20. 1 hit.
InterProIPR012674. Calycin.
IPR011038. Calycin-like.
IPR002345. Lipocalin.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
IPR002972. PstgldnD_synth.
[Graphical view]
PfamPF00061. Lipocalin. 1 hit.
[Graphical view]
PRINTSPR00179. LIPOCALIN.
PR01254. PGNDSYNTHASE.
SUPFAMSSF50814. SSF50814. 1 hit.
PROSITEPS00213. LIPOCALIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio607007.
PROP22057.

Entry information

Entry namePTGDS_RAT
AccessionPrimary (citable) accession number: P22057
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: February 1, 1996
Last modified: April 16, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families