O09114 (PTGDS_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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=L-PGDS
Short name=PGD2 synthase
Short name=PGDS2

Gene names

Name:

Ptgds

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	189 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.6 Ref.7 Ref.8 Ref.12 Ref.13 Ref.14
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.12 Ref.13
Subunit structure	Monomer By similarity.
Subcellular location	Rough endoplasmic reticulum By similarity. Nucleus membrane By similarity. Golgi apparatus By similarity. Cytoplasm › perinuclear 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.7 Ref.9
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.10
Domain	Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior. Ref.12 Ref.13 Ref.14
Sequence similarities	Belongs to the calycin superfamily. Lipocalin family.
Biophysicochemical properties	Kinetic parameters: KM=0.8 µM for prostaglandin H2 Ref.13 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 process	Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism Prostaglandin biosynthesis Prostaglandin metabolism Transport
Cellular component	Cytoplasm Endoplasmic reticulum Golgi apparatus Membrane Nucleus Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Isomerase
PTM	Disulfide bond Glycoprotein Pyrrolidone carboxylic acid
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	prostaglandin biosynthetic process Inferred from direct assay Ref.12. Source: UniProtKB regulation of circadian sleep/wake cycle, sleep Inferred from direct assay Ref.6. Source: UniProtKB response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi 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: Compara 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_function	fatty acid binding Inferred from electronic annotation. Source: Compara prostaglandin-D synthase activity Inferred from direct assay Ref.12. Source: UniProtKB retinoid binding Inferred from direct assay Ref.12. Source: UniProtKB small molecule binding Inferred from electronic annotation. Source: InterPro 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

By similarity

Chain

25 – 189

165

Prostaglandin-H2 D-isomerase

PRO_0000017947

Sites

Active site

65

1

Nucleophile

Amino acid modifications

Modified residue

25

1

Pyrrolidone carboxylic acid By similarity

Glycosylation

51

1

N-linked (GlcNAc...) By similarity

Glycosylation

78

1

N-linked (GlcNAc...) By similarity

Disulfide bond

89 ↔ 186

Ref.13

Natural variations

Alternative sequence

1 – 63

63

Missing in isoform 2.

VSP_041029

Experimental info

Mutagenesis

45

1

S → A: Reduces enzyme activity by about half. Reduces enzyme activity tenfold; when associated with A-67 and A-81. Ref.13

Mutagenesis

65

1

C → A: Loss of enzyme activity. No effect on ligand binding. Ref.13

Mutagenesis

67

1

T → A: Reduces enzyme activity by about half. Reduces enzyme activity tenfold; when associated with A-45 and A-81. Ref.13

Mutagenesis

81

1

S → A: Slightly reduced enzyme activity. half. Reduces enzyme activity tenfold; when associated with A-45 and A-67. Ref.13

Secondary structure

1

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189

Helix Strand Turn

Details...

Beta strand

27 – 29

3

Helix

36 – 39

4

Beta strand

41 – 50

10

Helix

55 – 58

4

Turn

59 – 61

3

Beta strand

66 – 71

6

Beta strand

75 – 85

11

Beta strand

89 – 98

10

Beta strand

104 – 107

4

Beta strand

110 – 113

4

Beta strand

116 – 124

9

Turn

125 – 127

3

Beta strand

128 – 134

7

Turn

137 – 140

4

Beta strand

144 – 154

11

Helix

157 – 169

13

Helix

174 – 176

3

Beta strand

177 – 179

3

Beta strand

184 – 187

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: C2C0B3E3B5928643	FASTA	189	21,066
	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
	Isoform 2 [UniParc]. Checksum: 7F9FEDCFBEFF99A6	FASTA	126	13,941
	10 20 30 40 50 60 MCKTVVAPST EGGLNLTSTF LRKNQCETKI MVLQPAGAPG HYTYSSPHSG SIHSVSVVEA 70 80 90 100 110 120 NYDEYALLFS RGTKGPGQDF RMATLYSRTQ TLKDELKEKF TTFSKAQGLT EEDIVFLPQP DKCIQE

References

	« Hide 'large scale' referencesShow '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 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.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
BC038083 mRNA. Translation: AAH38083.1.

IPI

IPI00114252.
IPI01016182.

PIR

S57748.

RefSeq

NP_032989.2. NM_008963.2.

UniGene

Mm.1008.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CZT	X-ray	2.00	A	25-189	[»]
2CZU	X-ray	2.10	A/B	25-189	[»]
2E4J	NMR	-	A	25-189	[»]
2KTD	NMR	-	A	25-189	[»]
2RQ0	NMR	-	A	25-189	[»]

ProteinModelPortal

O09114.

SMR

O09114. Positions 35-189.

ModBase

Search...

PTM databases

PhosphoSite

O09114.

Proteomic databases

PaxDb

O09114.

PRIDE

O09114.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000015234; ENSMUSP00000015234; ENSMUSG00000015090.
ENSMUST00000114251; ENSMUSP00000109889; ENSMUSG00000015090.
ENSMUST00000114259; ENSMUSP00000109897; ENSMUSG00000015090.

GeneID

19215.

KEGG

mmu:19215.

UCSC

uc008isf.1. mouse.

Organism-specific databases

CTD

5730.

MGI

MGI:99261. Ptgds.

Phylogenomic databases

eggNOG

NOG45731.

HOGENOM

HOG000231660.

HOVERGEN

HBG106490.

InParanoid

O09114.

KO

K01830.

OMA

WFREKKA.

OrthoDB

EOG4DV5NJ.

Enzyme and pathway databases

BRENDA

5.3.99.2. 3474.

Gene expression databases

ArrayExpress

O09114.

Bgee

O09114.

CleanEx

MM_PTGDS.

Genevestigator

O09114.

Family and domain databases

Gene3D

2.40.128.20. 1 hit.

InterPro

IPR012674. Calycin.
IPR011038. Calycin-like.
IPR002345. Lipocalin.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
IPR002972. PstgldnD_synth.
[Graphical view]

Pfam

PF00061. Lipocalin. 1 hit.
[Graphical view]

PRINTS

PR00179. LIPOCALIN.
PR01254. PGNDSYNTHASE.

SUPFAM

SSF50814. Calycin. 1 hit.

PROSITE

PS00213. LIPOCALIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O09114.

ChEMBL

CHEMBL4334.

ChiTaRS

PTGDS. mouse.

EvolutionaryTrace

O09114.

NextBio

295972.

SOURCE

Search...

Entry information

Entry name

PTGDS_MOUSE

Accession

Primary (citable) accession number: O09114
Secondary accession number(s): O09157, O35091, Q62169

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 1, 1997
Last modified:	May 29, 2013
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program