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O09114 (PTGDS_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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=L-PGDS
Short name=PGD2 synthase
Short name=PGDS2
Gene names
Name:Ptgds
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.1 Ref.4 Ref.8 Ref.9 Ref.10 Ref.14 Ref.15 Ref.16

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. Ref.14 Ref.15

Subunit structure

Monomer By similarity.

Subcellular location

Rough endoplasmic reticulum By similarity. Nucleus membrane By similarity. Golgi apparatus By similarity. Cytoplasmperinuclear region By similarity. Secreted By similarity. 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 By similarity.

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 male reproductive system, it is expressed in the testis, efferent ducts and epididymis, and is secreted into the seminal fluid. In the eye, it is expressed in the pigmented epithelium of the retina and the nonpigmented epithelium of the ciliary body, and secreted into the aqueous humor. Low levels detected in various tissue fluids such as serum, normal urine, ascitic fluid and tear fluid. Also found in a number of other organs including the ear, heart and lung. Ref.1 Ref.4 Ref.9 Ref.11

Developmental stage

Initially detected at 14.5 dpc in the mesenchymal cells of the brain. Later in development, observed in the choroid plexus and within single cells in the brain.

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.12

Domain

Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior. Ref.14 Ref.15 Ref.16

Sequence similarities

Belongs to the calycin superfamily. Lipocalin family.

Biophysicochemical properties

Kinetic parameters:

KM=0.8 µM for prostaglandin H2 Ref.15

Vmax=5.9 µmol/min/mg enzyme

Sequence caution

The sequence BAA21769.1 differs from that shown. Reason: Frameshift at position 47.

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
   Coding sequence diversityAlternative splicing
   DomainSignal
   Molecular functionIsomerase
   PTMDisulfide bond
Glycoprotein
Pyrrolidone carboxylic acid
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processprostaglandin biosynthetic process

Inferred from direct assay Ref.14. Source: UniProtKB

regulation of circadian sleep/wake cycle, sleep

Inferred from direct assay Ref.8. Source: UniProtKB

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

transport

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular region

Inferred from direct assay Ref.1. Source: UniProtKB

extracellular space

Inferred from electronic annotation. Source: Ensembl

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.14. Source: UniProtKB

retinoid binding

Inferred from direct assay Ref.14. Source: UniProtKB

transporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O09114-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O09114-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-63: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 By similarity
Chain25 – 189165Prostaglandin-H2 D-isomerase
PRO_0000017947

Sites

Active site651Nucleophile

Amino acid modifications

Modified residue251Pyrrolidone carboxylic acid By similarity
Glycosylation511N-linked (GlcNAc...) By similarity
Glycosylation781N-linked (GlcNAc...) By similarity
Disulfide bond89 ↔ 186 Ref.15

Natural variations

Alternative sequence1 – 6363Missing in isoform 2.
VSP_041029

Experimental info

Mutagenesis451S → A: Reduces enzyme activity by about half. Reduces enzyme activity tenfold; when associated with A-67 and A-81. Ref.15
Mutagenesis651C → A: Loss of enzyme activity. No effect on ligand binding. Ref.15
Mutagenesis671T → A: Reduces enzyme activity by about half. Reduces enzyme activity tenfold; when associated with A-45 and A-81. Ref.15
Mutagenesis811S → A: Slightly reduced enzyme activity. half. Reduces enzyme activity tenfold; when associated with A-45 and A-67. Ref.15

Secondary structure

................................. 189
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: C2C0B3E3B5928643

FASTA18921,066
        10         20         30         40         50         60 
MAALRMLWMG LVLLGLLGFP QTPAQGHDTV QPNFQQDKFL GRWYSAGLAS NSSWFREKKA 

        70         80         90        100        110        120 
VLYMCKTVVA PSTEGGLNLT STFLRKNQCE TKIMVLQPAG APGHYTYSSP HSGSIHSVSV 

       130        140        150        160        170        180 
VEANYDEYAL LFSRGTKGPG QDFRMATLYS RTQTLKDELK EKFTTFSKAQ GLTEEDIVFL 


PQPDKCIQE 

« Hide

Isoform 2 [UniParc].

Checksum: 7F9FEDCFBEFF99A6
Show »

FASTA12613,941

References

« Hide 'large scale' references
[1]"Developmental expression of murine Beta-trace in embryos and adult animals suggests a function in maturation and maintenance of blood-tissue barriers."
Hoffmann A., Baechner D., Betat N., Lauber J., Gross G.
Dev. Dyn. 207:332-343(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
Strain: NMRI.
Tissue: Brain.
[2]Hoffmann A., Steinert P., Lauber J., Gross G.
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]"Isolation of putative prostaglandin D synthetase from mouse choroid plexus."
Kita H., Kawamoto S., Okubo K., Matsubara K.
Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: C57BL/6.
Tissue: Brain.
[4]"Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice."
Eguchi N., Minami T., Shirafuji N., Kanaoka Y., Tanaka T., Nagata A., Yoshida N., Urade Y., Ito S., Hayaishi O.
Proc. Natl. Acad. Sci. U.S.A. 96:726-730(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
Strain: 129/Sv.
Tissue: Liver.
[5]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Small intestine.
[6]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Eye.
[8]"Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep."
Pinzar E., Kanaoka Y., Inui T., Eguchi N., Urade Y., Hayaishi O.
Proc. Natl. Acad. Sci. U.S.A. 97:4903-4907(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice."
Fujitani Y., Kanaoka Y., Aritake K., Uodome N., Okazaki-Hatake K., Urade Y.
J. Immunol. 168:443-449(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]"Perineuronal oligodendrocytes protect against neuronal apoptosis through the production of lipocalin-type prostaglandin D synthase in a genetic demyelinating model."
Taniike M., Mohri I., Eguchi N., Beuckmann C.T., Suzuki K., Urade Y.
J. Neurosci. 22:4885-4896(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Stage and region-specific localization of lipocalin-type prostaglandin D synthase in the adult murine testis and epididymis."
Gerena R.L., Eguchi N., Urade Y., Killian G.J.
J. Androl. 21:848-854(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[12]"Dexamethasone induces lipocalin-type prostaglandin D synthase gene expression in mouse neuronal cells."
Garcia-Fernandez L.F., Iniguez M.A., Eguchi N., Fresno M., Urade Y., Munoz A.
J. Neurochem. 75:460-470(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY DEXAMETHASONE.
[13]"Structural basis of multi-functional lipocalin-type prostaglandin D synthase."
RIKEN structural genomics initiative (RSGI)
Submitted (OCT-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 24-189.
[14]"NMR solution structure of lipocalin-type prostaglandin D synthase: evidence for partial overlapping of catalytic pocket and retinoic acid-binding pocket within the central cavity."
Shimamoto S., Yoshida T., Inui T., Gohda K., Kobayashi Y., Fujimori K., Tsurumura T., Aritake K., Urade Y., Ohkubo T.
J. Biol. Chem. 282:31373-31379(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 25-189, FUNCTION, CATALYTIC ACTIVITY, DOMAIN.
[15]"Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase."
Kumasaka T., Aritake K., Ago H., Irikura D., Tsurumura T., Yamamoto M., Miyano M., Urade Y., Hayaishi O.
J. Biol. Chem. 284:22344-22352(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 25-189 OF MUTANT ALA-65 IN COMPLEX WITH RETINOIC ACID, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF SER-45; CYS-65; THR-67 AND SER-81, BIOPHYSICOCHEMICAL PROPERTIES, DISULFIDE BOND, DOMAIN.
[16]"Structural analysis of lipocalin-type prostaglandin D synthase complexed with biliverdin by small-angle X-ray scattering and multi-dimensional NMR."
Miyamoto Y., Nishimura S., Inoue K., Shimamoto S., Yoshida T., Fukuhara A., Yamada M., Urade Y., Yagi N., Ohkubo T., Inui T.
J. Struct. Biol. 169:209-218(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 25-189 IN COMPLEX WITH BILIVERDIN, FUNCTION, DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X89222 mRNA. Translation: CAA61506.1.
Y10138 Genomic DNA. Translation: CAA71226.1.
AB006361 mRNA. Translation: BAA21769.1. Frameshift.
D83329 Genomic DNA. Translation: BAA74461.1.
AK131859 mRNA. Translation: BAE20833.1.
CH466542 Genomic DNA. Translation: EDL08250.1.
CH466542 Genomic DNA. Translation: EDL08251.1.
BC038083 mRNA. Translation: AAH38083.1.
BC043015 mRNA. Translation: AAH43015.1.
PIRS57748.
RefSeqNP_032989.2. NM_008963.2.
XP_006497849.1. XM_006497786.1.
XP_006497850.1. XM_006497787.1.
UniGeneMm.1008.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CZTX-ray2.00A25-189[»]
2CZUX-ray2.10A/B25-189[»]
2E4JNMR-A25-189[»]
2KTDNMR-A25-189[»]
2RQ0NMR-A25-189[»]
ProteinModelPortalO09114.
SMRO09114. Positions 35-189.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBO09114.
ChEMBLCHEMBL4334.

PTM databases

PhosphoSiteO09114.

Proteomic databases

PaxDbO09114.
PRIDEO09114.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000015234; ENSMUSP00000015234; ENSMUSG00000015090. [O09114-1]
ENSMUST00000114251; ENSMUSP00000109889; ENSMUSG00000015090. [O09114-1]
ENSMUST00000114259; ENSMUSP00000109897; ENSMUSG00000015090. [O09114-1]
GeneID19215.
KEGGmmu:19215.
UCSCuc008isf.1. mouse. [O09114-1]

Organism-specific databases

CTD5730.
MGIMGI:99261. Ptgds.

Phylogenomic databases

eggNOGNOG45731.
HOGENOMHOG000231660.
HOVERGENHBG106490.
InParanoidO09114.
KOK01830.
OMAPGQDFRM.
OrthoDBEOG78PVBH.
PhylomeDBO09114.
TreeFamTF336103.

Enzyme and pathway databases

BRENDA5.3.99.2. 3474.

Gene expression databases

BgeeO09114.
CleanExMM_PTGDS.
GenevestigatorO09114.

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

ChiTaRSPTGDS. mouse.
EvolutionaryTraceO09114.
NextBio295972.
PROO09114.
SOURCESearch...

Entry information

Entry namePTGDS_MOUSE
AccessionPrimary (citable) accession number: O09114
Secondary accession number(s): O09157 expand/collapse secondary AC list , O35091, Q3V2G5, Q62169
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 128 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot