O60760 (HPGDS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13
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.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 RX + glutathione = HX + R-S-glutathione. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13
Cofactor	Glutathione. Required for the prostaglandin D synthase activity. Ref.1 Ref.2 Ref.7 Ref.8
Enzyme regulation	Prostaglandin PGD2 synthesis is stimulated by calcium and magnesium ions. One calcium or magnesium ion is bound between the subunits of the homodimer. The interactions with the protein are for the most part mediated via water molecules. Magnesium increases the affinity for glutathione, while calcium has no effect on the affinity for glutathione. Ref.9
Subunit structure	Homodimer. Ref.9 Ref.10 Ref.12
Subcellular location	Cytoplasm Ref.8.
Tissue specificity	Expressed in a number of megakaryocytic cell lines but not in platelets. Highly expressed in adipose tissue, macrophages and placenta. Also expressed at lower levels in lung, heart, lymph nodes, appendix, bone marrow and fetal liver. Ref.1 Ref.2 Ref.7 Ref.8
Developmental stage	Highest levels in immature megakaryocytic cells. Disappears after final differentiation to platelets. Ref.7
Induction	By 12-O-tetradecanoylphorbol-13-acetate (TPA). Ref.7 Ref.9
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: KM=8 mM for glutathione for the glutathione-conjugating activity Ref.2 Ref.9 Ref.10 KM=0.6 mM for glutathione for the prostaglandin D synthase activity in the presence of EDTA KM=0.14 mM for glutathione for the prostaglandin D synthase activity in the presence of magnesium ions Vmax=8.6 µmol/min/mg enzyme with 1-bromo-2,4-dinitrobenzene as substrate Vmax=5.1 µmol/min/mg enzyme with 1-chloro-2,4-dinitrobenzene as substrate Vmax=44.3 µmol/min/mg enzyme with 1-fluoro-2,4-dinitrobenzene as substrate Vmax=10.7 µmol/min/mg enzyme with 1-iodo-2,4-dinitrobenzene as substrate Vmax=6.8 µmol/min/mg enzyme with allyl isothiocyanate as substrate Vmax=6.3 µmol/min/mg enzyme with benzyl isothiocyanate as substrate Vmax=0.05 µmol/min/mg enzyme with cumene hydroperoxide as substrate

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism Prostaglandin biosynthesis Prostaglandin metabolism
Cellular component	Cytoplasm
Ligand	Calcium Magnesium Metal-binding
Molecular function	Isomerase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	locomotory behavior Traceable author statement PubMed 10781097. Source: ProtInc prostaglandin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW prostaglandin metabolic process Inferred from direct assay Ref.9. Source: UniProtKB signal transduction Non-traceable author statement Ref.8. Source: ProtInc
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	calcium ion binding Inferred from direct assay Ref.9. Source: UniProtKB glutathione transferase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from direct assay Ref.9. Source: UniProtKB prostaglandin-D synthase activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 199

198

Hematopoietic prostaglandin D synthase

PRO_0000185934

Regions

Domain

2 – 79

78

GST N-terminal

Domain

81 – 199

119

GST C-terminal

Region

63 – 64

2

Glutathione binding

Sites

Binding site

8

1

Glutathione

Binding site

14

1

Glutathione

Binding site

39

1

Glutathione

Binding site

51

1

Glutathione; via amide nitrogen and carbonyl oxygen

Experimental info

Mutagenesis

93

1

D → N: Loss of activation by calcium or magnesium ions. Ref.9

Mutagenesis

96

1

D → N: Increases PGD2 synthesis. Loss of activation by calcium or magnesium ions. Ref.9

Mutagenesis

97

1

D → N: Reduces PGD2 synthesis by 99%. Loss of activation by calcium or magnesium ions. Ref.9

Sequence conflict

187

1

V → I no nucleotide entry Ref.2

Secondary structure

1

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199

Helix Strand Turn

Details...

Beta strand

4 – 12

9

Helix

13 – 15

3

Helix

16 – 24

9

Beta strand

30 – 34

5

Helix

36 – 38

3

Helix

39 – 43

5

Beta strand

46 – 49

4

Beta strand

53 – 56

4

Beta strand

59 – 62

4

Helix

64 – 72

9

Helix

76 – 78

3

Helix

82 – 100

19

Helix

109 – 121

13

Helix

123 – 135

13

Beta strand

139 – 142

4

Helix

148 – 163

16

Turn

165 – 170

6

Helix

172 – 182

11

Helix

185 – 193

9

Sequences

	Sequence		Length	Mass (Da)
	O60760 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: A4ED2476B16CC5C3	FASTA	199	23,344
	10 20 30 40 50 60 MPNYKLTYFN MRGRAEIIRY IFAYLDIQYE DHRIEQADWP EIKSTLPFGK IPILEVDGLT 70 80 90 100 110 120 LHQSLAIARY LTKNTDLAGN TEMEQCHVDA IVDTLDDFMS CFPWAEKKQD VKEQMFNELL 130 140 150 160 170 180 TYNAPHLMQD LDTYLGGREW LIGNSVTWAD FYWEICSTTL LVFKPDLLDN HPRLVTLRKK 190 VQAIPAVANW IKRRPQTKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase." Kanaoka Y., Fujimori K., Kikuno R., Sakaguchi Y., Urade Y., Hayaishi O. Eur. J. Biochem. 267:3315-3322(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR, TISSUE SPECIFICITY. Tissue: Placenta.
[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: Placenta.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Substantia nigra.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Placenta.
[7]	"Induction of hematopoietic prostaglandin D synthase in human megakaryocytic cells by phorbol ester." Suzuki T., Watanabe K., Kanaoka Y., Sato T., Hayaishi O. Biochem. Biophys. Res. Commun. 241:288-293(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION. Tissue: Megakaryocyte.
[8]	"Prostaglandin D synthase in human megakaryoblastic cells." Mahmud I., Ueda N., Yamaguchi H., Yamashita R., Yamamoto S., Kanaoka Y., Urade Y., Hayaishi O. J. Biol. Chem. 272:28263-28266(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Megakaryocyte.
[9]	"Mechanism of metal activation of human hematopoietic prostaglandin D synthase." Inoue T., Irikura D., Okazaki N., Kinugasa S., Matsumura H., Uodome N., Yamamoto M., Kumasaka T., Miyano M., Kai Y., Urade Y. Nat. Struct. Biol. 10:291-296(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEXES WITH CALCIUM IONS; MAGNESIUM IONS AND GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-93; ASP-96 AND ASP-97.
[10]	"First determination of the inhibitor complex structure of human hematopoietic prostaglandin D synthase." Inoue T., Okano Y., Kado Y., Aritake K., Irikura D., Uodome N., Okazaki N., Kinugasa S., Shishitani H., Matsumura H., Kai Y., Urade Y. J. Biochem. 135:279-283(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS AND THE SYNTHETIC INHIBITOR BSBT, FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[11]	"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: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE; MAGNESIUM IONS AND THE SYNTHETIC INHIBITOR HQL-79, FUNCTION, CATALYTIC ACTIVITY.
[12]	"Novel prostaglandin D synthase inhibitors generated by fragment-based drug design." Hohwy M., Spadola L., Lundquist B., Hawtin P., Dahmen J., Groth-Clausen I., Nilsson E., Persdotter S., von Wachenfeldt K., Folmer R.H., Edman K. J. Med. Chem. 51:2178-2186(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH SYNTHETIC INHIBITORS, SUBUNIT.
[13]	"Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D2 synthase." Weber J.E., Oakley A.J., Christ A.N., Clark A.G., Hayes J.D., Hall R., Hume D.A., Board P.G., Smythe M.L., Flanagan J.U. Eur. J. Med. Chem. 45:447-454(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR, CATALYTIC ACTIVITY, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D82073 mRNA. Translation: BAA25545.1.
AB008830 Genomic DNA. Translation: BAA96854.1.
AK290075 mRNA. Translation: BAF82764.1.
CR541662 mRNA. Translation: CAG46463.1.
CR541679 mRNA. Translation: CAG46480.1.
CH471057 Genomic DNA. Translation: EAX06052.1.
BC020734 mRNA. Translation: AAH20734.1.

IPI

IPI00219303.

RefSeq

NP_055300.1. NM_014485.2.

UniGene

Hs.128433.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IYH	X-ray	1.70	A/B/C/D	2-198	[»]
1IYI	X-ray	1.80	A/B/C/D	2-198	[»]
1V40	X-ray	1.90	A/B/C/D	2-198	[»]
2CVD	X-ray	1.45	A/B/C/D	2-198	[»]
2VCQ	X-ray	1.95	A/B/C/D	1-199	[»]
2VCW	X-ray	1.95	A/B/C/D	1-199	[»]
2VCX	X-ray	2.10	A/B/C/D	1-199	[»]
2VCZ	X-ray	1.95	A/B/C/D	1-199	[»]
2VD0	X-ray	2.20	A/B/C/D	1-199	[»]
2VD1	X-ray	2.25	A/B/C/D	1-199	[»]
3EE2	X-ray	1.91	A/B	1-199	[»]
3KXO	X-ray	2.10	A/B	1-199	[»]
3VI5	X-ray	2.00	A/B/C/D	2-199	[»]
3VI7	X-ray	2.00	A/B/C/D	2-199	[»]
4EC0	X-ray	1.85	A/B	1-199	[»]
4EDY	X-ray	1.72	A/B	2-199	[»]
4EDZ	X-ray	2.00	A/B/C/D	2-199	[»]
4EE0	X-ray	1.75	A/B	2-199	[»]

ProteinModelPortal

O60760.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000295256.

PTM databases

PhosphoSite

O60760.

Proteomic databases

PaxDb

O60760.

PRIDE

O60760.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000295256; ENSP00000295256; ENSG00000163106.

GeneID

27306.

KEGG

hsa:27306.

UCSC

uc003hte.1. human.

Organism-specific databases

CTD

27306.

GeneCards

GC04M095219.

HGNC

HGNC:17890. HPGDS.

HPA

CAB020805.
HPA024035.

MIM

602598. gene.

neXtProt

NX_O60760.

PharmGKB

PA165664133.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG122057.

HOGENOM

HOG000115733.

HOVERGEN

HBG105321.

InParanoid

O60760.

KO

K01830.

OMA

MSCFPWA.

OrthoDB

EOG4H9XMH.

PhylomeDB

O60760.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

O60760.

Bgee

O60760.

Genevestigator

O60760.

GermOnline

ENSG00000163106. Homo sapiens.

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

BindingDB

O60760.

ChEMBL

CHEMBL5879.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

O60760.

GenomeRNAi

27306.

NextBio

50305.

SOURCE

Search...

Entry information

Entry name

HPGDS_HUMAN

Accession

Primary (citable) accession number: O60760
Secondary accession number(s): Q6FHT9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 127 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.