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P22437 (PGH1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prostaglandin G/H synthase 1

EC=1.14.99.1
Alternative name(s):
Cyclooxygenase-1
Short name=COX-1
Prostaglandin H2 synthase 1
Short name=PGH synthase 1
Short name=PGHS-1
Short name=PHS 1
Prostaglandin-endoperoxide synthase 1
Gene names
Name:Ptgs1
Synonyms:Cox-1, Cox1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length602 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.

Catalytic activity

Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.

Cofactor

Binds 1 heme B (iron-protoporphyrin IX) group per subunit By similarity.

Pathway

Lipid metabolism; prostaglandin biosynthesis.

Subunit structure

Homodimer.

Subcellular location

Microsome membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein.

Miscellaneous

The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site.

Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PGHS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine-tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PGHS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation.

PTGS1 and PTGS2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration.

Sequence similarities

Belongs to the prostaglandin G/H synthase family.

Contains 1 EGF-like domain.

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
Prostaglandin biosynthesis
Prostaglandin metabolism
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   DomainEGF-like domain
Signal
   LigandHeme
Iron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
Peroxidase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcyclooxygenase pathway

Inferred from electronic annotation. Source: Ensembl

keratinocyte differentiation

Non-traceable author statement PubMed 12067981. Source: UniProtKB

prostaglandin biosynthetic process

Inferred from mutant phenotype PubMed 12093889. Source: MGI

prostaglandin metabolic process

Inferred from mutant phenotype PubMed 10987272. Source: MGI

regulation of blood pressure

Inferred from mutant phenotype PubMed 12093889. Source: MGI

regulation of cell proliferation

Inferred from genetic interaction PubMed 10987272. Source: MGI

response to oxidative stress

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 12021206PubMed 12355421. Source: MGI

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

photoreceptor outer segment

Inferred from direct assay PubMed 12355421. Source: MGI

   Molecular_functiondioxygenase activity

Inferred from electronic annotation. Source: UniProtKB-KW

heme binding

Inferred from electronic annotation. Source: InterPro

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

peroxidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

prostaglandin-endoperoxide synthase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626
Chain27 – 602576Prostaglandin G/H synthase 1
PRO_0000023869

Regions

Domain34 – 7239EGF-like

Sites

Active site2091Proton acceptor By similarity
Active site3871For cyclooxygenase activity By similarity
Metal binding3901Iron (heme axial ligand) By similarity
Site5321Aspirin-acetylated serine

Amino acid modifications

Glycosylation701N-linked (GlcNAc...) Potential
Glycosylation1061N-linked (GlcNAc...) Potential
Glycosylation1461N-linked (GlcNAc...) Potential
Disulfide bond38 ↔ 49 By similarity
Disulfide bond39 ↔ 161 By similarity
Disulfide bond43 ↔ 59 By similarity
Disulfide bond61 ↔ 71 By similarity
Disulfide bond571 ↔ 577 By similarity

Sequences

Sequence LengthMass (Da)Tools
P22437 [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: 634C0E602045C3A0

FASTA60269,042
        10         20         30         40         50         60 
MSRRSLSLWF PLLLLLLLPP TPSVLLADPG VPSPVNPCCY YPCQNQGVCV RFGLDNYQCD 

        70         80         90        100        110        120 
CTRTGYSGPN CTIPEIWTWL RNSLRPSPSF THFLLTHGYW LWEFVNATFI REVLMRLVLT 

       130        140        150        160        170        180 
VRSNLIPSPP TYNSAHDYIS WESFSNVSYY TRILPSVPKD CPTPMGTKGK KQLPDVQLLA 

       190        200        210        220        230        240 
QQLLLRREFI PAPQGTNILF AFFAQHFTHQ FFKTSGKMGP GFTKALGHGV DLGHIYGDNL 

       250        260        270        280        290        300 
ERQYHLRLFK DGKLKYQVLD GEVYPPSVEQ ASVLMRYPPG VPPERQMAVG QEVFGLLPGL 

       310        320        330        340        350        360 
MLFSTIWLRE HNRVCDLLKE EHPTWDDEQL FQTTRLILIG ETIKIVIEEY VQHLSGYFLQ 

       370        380        390        400        410        420 
LKFDPELLFR AQFQYRNRIA MEFNHLYHWH PLMPNSFQVG SQEYSYEQFL FNTSMLVDYG 

       430        440        450        460        470        480 
VEALVDAFSR QRAGRIGGGR NFDYHVLHVA VDVIKESREM RLQPFNEYRK RFGLKPYTSF 

       490        500        510        520        530        540 
QELTGEKEMA AELEELYGDI DALEFYPGLL LEKCQPNSIF GESMIEMGAP FSLKGLLGNP 

       550        560        570        580        590        600 
ICSPEYWKPS TFGGDVGFNL VNTASLKKLV CLNTKTCPYV SFRVPDYPGD DGSVLVRRST 


EL 

« Hide

References

« Hide 'large scale' references
[1]"The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases."
Dewitt D.L., El-Harith E.A., Kraemer S.A., Andrews M.J., Yao E.F., Armstrong R.L., Smith W.L.
J. Biol. Chem. 265:5192-5198(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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].
Strain: FVB/N.
Tissue: Mammary gland.
[3]"Cyclooxygenases: structural, cellular, and molecular biology."
Smith W.L., DeWitt D.L., Garavito R.M.
Annu. Rev. Biochem. 69:145-182(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION; TISSUE SPECIFICITY AND INHIBITION BY NSAIDS.
[4]"Aspirin, cyclooxygenase inhibition and colorectal cancer."
Sostres C., Gargallo C.J., Lanas A.
World J. Gastrointest. Pharmacol. Ther. 5:40-49(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL CANCER.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M34141 mRNA. Translation: AAA39913.1.
BC005573 mRNA. Translation: AAH05573.1.
CCDSCCDS15970.1.
PIRA35564.
RefSeqNP_032995.1. NM_008969.4.
XP_006497853.1. XM_006497790.1.
XP_006497854.1. XM_006497791.1.
XP_006497855.1. XM_006497792.1.
XP_006497856.1. XM_006497793.1.
UniGeneMm.275434.

3D structure databases

ProteinModelPortalP22437.
SMRP22437. Positions 34-586.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202462. 2 interactions.
IntActP22437. 3 interactions.
MINTMINT-4107353.

Chemistry

BindingDBP22437.
ChEMBLCHEMBL2649.

Protein family/group databases

PeroxiBase3361. MmPGHS01.

PTM databases

PhosphoSiteP22437.

Proteomic databases

MaxQBP22437.
PaxDbP22437.
PRIDEP22437.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000062069; ENSMUSP00000059977; ENSMUSG00000047250.
GeneID19224.
KEGGmmu:19224.
UCSCuc008jll.1. mouse.

Organism-specific databases

CTD5742.
MGIMGI:97797. Ptgs1.

Phylogenomic databases

eggNOGNOG39991.
HOGENOMHOG000013149.
HOVERGENHBG000366.
InParanoidP22437.
KOK00509.
OMAFKTSGKM.
OrthoDBEOG7RFTHC.
PhylomeDBP22437.
TreeFamTF329675.

Enzyme and pathway databases

UniPathwayUPA00662.

Gene expression databases

ArrayExpressP22437.
BgeeP22437.
CleanExMM_PTGS1.
GenevestigatorP22437.

Family and domain databases

Gene3D1.10.640.10. 1 hit.
InterProIPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR002007. Haem_peroxidase_animal.
IPR019791. Haem_peroxidase_animal_subgr.
[Graphical view]
PfamPF03098. An_peroxidase. 2 hits.
[Graphical view]
PRINTSPR00457. ANPEROXIDASE.
SMARTSM00181. EGF. 1 hit.
[Graphical view]
SUPFAMSSF48113. SSF48113. 1 hit.
PROSITEPS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio296008.
PROP22437.
SOURCESearch...

Entry information

Entry namePGH1_MOUSE
AccessionPrimary (citable) accession number: P22437
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: July 9, 2014
This is version 149 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

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