Hematopoietic prostaglandin D synthase - Rattus norvegicus (Rat)

Contribute

Send feedback

Read comments (?) or add your own

O35543 (HPGDS_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 116. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Hematopoietic prostaglandin D synthase
Short name=H-PGDS
EC=5.3.99.2

Alternative name(s):
GST class-sigma
Glutathione S-transferase
EC=2.5.1.18
Glutathione-dependent PGD synthase
Glutathione-requiring prostaglandin D synthase
Prostaglandin-H2 D-isomerase

Gene names

Name:	Hpgds
Synonyms:	Gsts, Pgds, Ptgds2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	199 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	Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide. Ref.1 Ref.2 Ref.5 Ref.6
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.1 Ref.2 Ref.5 Ref.6 RX + glutathione = HX + R-S-glutathione. Ref.1 Ref.2 Ref.5 Ref.6
Cofactor	Glutathione. Required for the prostaglandin D synthase activity. Ref.2 Ref.5
Subunit structure	Homodimer. Ref.1
Subcellular location	Cytoplasm.
Tissue specificity	Highly expressed in spleen and bone marrow. Lower levels of expression in small intestine, colon, liver, pancreas and skin. Not detected in brain, heart, lung or kidney (at protein level). Ref.1 Ref.2
Sequence similarities	Belongs to the GST superfamily. Sigma family. Contains 1 GST C-terminal domain. Contains 1 GST N-terminal domain.
Biophysicochemical properties	Kinetic parameters: K_M=100 µM for glutathione for the prostaglandin D synthase activity Ref.2 Ref.5 K_M=500 µM for glutathione for the glutathione-conjugating activity K_M=500 µM for PGH2 for the prostaglandin D synthase activity K_M=3 mM for 1-chloro-2,4-dinitrobenzene V_max=17.6 µmol/min/mg enzyme with 1-bromo-2,4-dinitrobenzene as substrate V_max=9.2 µmol/min/mg enzyme with 1-chloro-2,4-dinitrobenzene as substrate V_max=48.3 µmol/min/mg enzyme with 1-fluoro-2,4-dinitrobenzene as substrate V_max=17.9 µmol/min/mg enzyme with 1-iodo-2,4-dinitrobenzene as substrate V_max=0.35 µmol/min/mg enzyme with cumene hydroperoxide as substrate V_max=10.2 µmol/min/mg enzyme with allyl isothiocyanate as substrate V_max=11.3 µmol/min/mg enzyme with benzyl isothiocyanate as substrate
Sequence caution	The sequence AAB72099.1 differs from that shown. Reason: Frameshift at positions 73 and 113.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism Prostaglandin biosynthesis Prostaglandin metabolism
Cellular component	Cytoplasm
Molecular function	Isomerase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	prostaglandin biosynthetic process Traceable author statement Ref.1. Source: RGD
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	calcium ion binding Inferred from sequence or structural similarity. Source: UniProtKB glutathione transferase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB prostaglandin-D synthase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed

Chain

2 – 199

198

Hematopoietic prostaglandin D synthase

PRO_0000185936

Regions

Domain

2 – 79

GST N-terminal

Domain

81 – 199

119

GST C-terminal

Region

63 – 64

Glutathione binding

Sites

Binding site

Glutathione

Binding site

Glutathione

Binding site

Glutathione

Binding site

Glutathione; via amide nitrogen and carbonyl oxygen

Experimental info

Mutagenesis

Y → F: Moderate reduction of protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. Ref.5

Mutagenesis

R → E: Moderate reduction of protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. Ref.5

Mutagenesis

R → K: Moderate reduction of protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. Ref.5

Mutagenesis

104

W → I: No significant effect on protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. Ref.5

Mutagenesis

112

K → E: Significant reduction of protein expression levels. Significantly reduces prostaglandin D synthase and moderately reduces glutathione-conjugating activities. Ref.5

Mutagenesis

152

Y → F: Significant reduction of protein expression levels. Moderately reduces prostaglandin D synthase activity. Ref.5

Mutagenesis

156

C → L: No significant effect on protein expression levels. Abolishes prostaglandin D synthase and significantly reduces glutathione-conjugating activities. Ref.5

Mutagenesis

156

C → Y: Significant reduction of protein expression levels. Abolishes prostaglandin D synthase and significantly reduces glutathione-conjugating activities. Ref.5

Mutagenesis

198

K → E: Moderate reduction of protein expression levels. No significant effect on catalytic activities. Ref.5

Mutagenesis

199

L → F: Moderate reduction of protein expression levels. No significant effect on catalytic activities. Ref.5

Sequence conflict

194

R → S in AAB72099. Ref.4

Secondary structure

199

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

O35543 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E5EF934D89DC240F
Show »

FASTA

199

23,297

        10         20         30         40         50         60 
MPNYKLLYFN MRGRAEIIRY IFAYLDIKYE DHRIEQADWP KIKPTLPFGK IPVLEVEGLT 

        70         80         90        100        110        120 
LHQSLAIARY LTKNTDLAGK TELEQCQVDA VVDTLDDFMS LFPWAEENQD LKERTFNDLL 

       130        140        150        160        170        180 
TRQAPHLLKD LDTYLGDKEW FIGNYVTWAD FYWDICSTTL LVLKPDLLGI YPRLVSLRNK 

       190 
VQAIPAISAW ILKRPQTKL

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and crystal structure of hematopoietic prostaglandin D synthase." Kanaoka Y., Ago H., Inagaki E., Nanayama T., Miyano M., Kikuno R., Fujii Y., Eguchi N., Toh H., Urade Y., Hayaishi O. Cell 90:1085-1095(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Spleen.
[2]	"Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases." Jowsey I.R., Thomson A.M., Flanagan J.U., Murdock P.R., Moore G.B., Meyer D.J., Murphy G.J., Smith S.A., Hayes J.D. Biochem. J. 359:507-516(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Tissue: Spleen.
[3]	"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]. Tissue: Ovary.
[4]	"Purification and cloning of rat glutathione-dependent prostaglandin D synthase." Yuan Y., Reddy R.G., Kim H. Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 39-198. Strain: Sprague-Dawley. Tissue: Spleen.
[5]	"Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis." Pinzar E., Miyano M., Kanaoka Y., Urade Y., Hayaishi O. J. Biol. Chem. 275:31239-31244(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-8; ARG-14; TRP-104; LYS-112; TYR-152; CYS-156; LYS-198 AND LEU-199.
[6]	"Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase." Aritake K., Kado Y., Inoue T., Miyano M., Urade Y. J. Biol. Chem. 281:15277-15286(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D82071 mRNA. Translation: BAA22898.1.
BC087590 mRNA. Translation: AAH87590.1.
AF021882 mRNA. Translation: AAB72099.1. Frameshift.

IPI

IPI00231248.

RefSeq

NP_113832.1. NM_031644.2.

UniGene

Rn.10837.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PD2	X-ray	2.30	1/2	1-199	[»]

ProteinModelPortal

O35543.

SMR

O35543. Positions 1-199.

ModBase

Search...

Proteomic databases

PRIDE

O35543.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000008826; ENSRNOP00000008826; ENSRNOG00000006583.

GeneID

58962.

KEGG

rno:58962.

UCSC

RGD:69251. rat.

Organism-specific databases

CTD

27306.

RGD

69251. Hpgds.

Phylogenomic databases

eggNOG

NOG122057.

GeneTree

ENSGT00550000074559.

HOGENOM

HOG000115733.

HOVERGEN

HBG105321.

InParanoid

O35543.

K01830.

OMA

AIAAWIQ.

OrthoDB

EOG4H9XMH.

Gene expression databases

Genevestigator

O35543.

GermOnline

ENSRNOG00000006583. Rattus norvegicus.

Family and domain databases

Gene3D

1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.

InterPro

IPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR017933. Glutathione_S_Trfase/Cl_chnl_C.
IPR004046. GST_C.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

Pfam

PF00043. GST_C. 1 hit.
PF02798. GST_N. 1 hit.
[Graphical view]

SUPFAM

SSF47616. GST_C_like. 1 hit.
SSF52833. Thiordxn-like_fd. 1 hit.

PROSITE

PS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O35543.

NextBio

611604.

Entry information

Entry name

HPGDS_RAT

Accession

Primary (citable) accession number: O35543
Secondary accession number(s): O35351

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 116 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents