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Q63921 (PGH1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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 By similarity.

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_processaging

Inferred from expression pattern PubMed 17499644. Source: RGD

learning

Inferred from mutant phenotype PubMed 21701788. Source: RGD

maintenance of blood-brain barrier

Inferred from mutant phenotype PubMed 17704356. Source: RGD

memory

Inferred from mutant phenotype PubMed 21701788. Source: RGD

negative regulation of epinephrine secretion

Inferred from mutant phenotype PubMed 18598693. Source: RGD

negative regulation of norepinephrine secretion

Inferred from mutant phenotype PubMed 18598693. Source: RGD

positive regulation of smooth muscle contraction

Inferred from mutant phenotype PubMed 18480553. Source: RGD

positive regulation of vasoconstriction

Inferred from mutant phenotype PubMed 18456673. Source: RGD

prostaglandin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of blood pressure

Inferred from sequence or structural similarity. Source: UniProtKB

response to corticosterone

Inferred from expression pattern PubMed 18584335. Source: RGD

response to fatty acid

Inferred from expression pattern PubMed 16983392. Source: RGD

response to organonitrogen compound

Inferred from expression pattern PubMed 11211925. Source: RGD

response to oxidative stress

Inferred from electronic annotation. Source: InterPro

sensory perception of pain

Inferred from mutant phenotype PubMed 21362433. Source: RGD

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

intracellular membrane-bounded organelle

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear envelope

Inferred from direct assay PubMed 12657565. Source: RGD

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functiondioxygenase activity

Inferred from electronic annotation. Source: UniProtKB-KW

heme binding

Inferred from electronic annotation. Source: InterPro

lipid binding

Inferred from mutant phenotype PubMed 17245358. Source: RGD

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

peroxidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

prostaglandin-endoperoxide synthase activity

Traceable author statement PubMed 12657565. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 By similarity
Chain27 – 602576Prostaglandin G/H synthase 1
PRO_0000023870

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
Glycosylation4121N-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

Experimental info

Sequence conflict361N → I in AAA03465. Ref.1
Sequence conflict361N → I in AAB29400. Ref.1
Sequence conflict116 – 1172RL → GW Ref.1
Sequence conflict1191I → L Ref.1
Sequence conflict1921G → A in AAA03465. Ref.1
Sequence conflict1921G → A in AAB29400. Ref.1
Sequence conflict2631V → L in AAA03465. Ref.1
Sequence conflict2631V → L in AAB29400. Ref.1
Sequence conflict2741L → K in AAA03465. Ref.1
Sequence conflict2741L → K in AAB29400. Ref.1
Sequence conflict2901G → A in AAA03465. Ref.1
Sequence conflict2901G → A in AAB29400. Ref.1
Sequence conflict3391I → R in AAB29400. Ref.1
Sequence conflict3441K → E in AAA03465. Ref.1
Sequence conflict3441K → E in AAB29400. Ref.1
Sequence conflict3811L → M in AAA03465. Ref.1
Sequence conflict3811L → M in AAB29400. Ref.1
Sequence conflict3921L → F in AAA03465. Ref.1
Sequence conflict3921L → F in AAB29400. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q63921 [UniParc].

Last modified December 15, 1998. Version 2.
Checksum: 0BFAF7EBFDA0C7C2

FASTA60269,032
        10         20         30         40         50         60 
MSRRSLSLQF PLLLLLLLLP PPPVLLTDAG VPSPVNPCCY YPCQNQGVCV RFGLDHYQCD 

        70         80         90        100        110        120 
CTRTGYSGPN CTIPEIWTWL RSSLRPSPSF THFLLTHGYW IWEFVNATFI REVLMRLVIT 

       130        140        150        160        170        180 
VRSNLIPSPP TYNTAHDYIS WESFSNVSYY TRILPSVPKD CPTPMGTKGK KQLPDIHLLA 

       190        200        210        220        230        240 
QRLLLRREFI PGPQGTNVLF AFFAQHFTHQ FFKTSGKMGP GFTKALGHGV DLGHIYGDSL 

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

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

       370        380        390        400        410        420 
LKFDPELLFR AQFQYRNRIA LEFNHLYHWH PLMPDSFQVG SQEYSYEQFL FNTSMLVDYG 

       430        440        450        460        470        480 
VEALVDAFSR QRAGRIGGGR NFDYHVLHVA EDVIKESREM RLQSFNEYRK RFGLKPYTSF 

       490        500        510        520        530        540 
QEFTGEKEMA AELEELYGDI DALEFYPGLM LEKCQPNSLF GESMIEMGAP FSLKGLLGNP 

       550        560        570        580        590        600 
ICSPEYWKPS TFGGDVGFNI VNTASLKKLV CLNTKTCPYV SFRVPDYPGD DGSVFVRPST 


EL 

« Hide

References

[1]"Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression."
Feng L., Sun W., Xia Y., Tang W.W., Chanmugam P., Soyoola E., Wilson C.B., Hwang D.
Arch. Biochem. Biophys. 307:361-368(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
[2]"Analysis and quantitation of splicing variants of the TPA-inducible PGHS-1 mRNA in rat tracheal epithelial cells."
Kitzler J., Hill E., Hardman R., Reddy N., Philpot R., Eling T.E.
Arch. Biochem. Biophys. 316:856-863(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Fischer 344.
Tissue: Trachea.
[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
U03388 mRNA. Translation: AAA03465.1.
S67721 mRNA. Translation: AAB29400.2.
U18060 mRNA. Translation: AAA85823.1.
PIRS39782.
S69198.
UniGeneRn.44404.

3D structure databases

ProteinModelPortalQ63921.
SMRQ63921. Positions 34-586.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000010218.

Chemistry

BindingDBQ63921.
ChEMBLCHEMBL2095157.

Protein family/group databases

PeroxiBase3974. RnoPGHS01.

Proteomic databases

PaxDbQ63921.
PRIDEQ63921.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

KEGGrno:24693.
UCSCRGD:3439. rat.

Organism-specific databases

RGD3439. Ptgs1.

Phylogenomic databases

eggNOGNOG39991.
HOGENOMHOG000013149.
HOVERGENHBG000366.
InParanoidQ63921.
PhylomeDBQ63921.

Enzyme and pathway databases

UniPathwayUPA00662.

Gene expression databases

GenevestigatorQ63921.

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

NextBio604139.
PROQ63921.

Entry information

Entry namePGH1_RAT
AccessionPrimary (citable) accession number: Q63921
Secondary accession number(s): Q62731, Q63684
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: December 15, 1998
Last modified: July 9, 2014
This is version 132 of the entry and version 2 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