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P79208 (PGH2_SHEEP) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. 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 2

EC=1.14.99.1
Alternative name(s):
Cyclooxygenase-2
Short name=COX-2
PHS II
Prostaglandin H2 synthase 2
Short name=PGH synthase 2
Short name=PGHS-2
Prostaglandin-endoperoxide synthase 2
Gene names
Name:PTGS2
Synonyms:COX2
OrganismOvis aries (Sheep) [Reference proteome]
Taxonomic identifier9940 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis

Protein attributes

Sequence length603 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis. Ref.3

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.

Post-translational modification

S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-525 By similarity.

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
   DomainSignal
   LigandHeme
Iron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
Peroxidase
   PTMDisulfide bond
Glycoprotein
S-nitrosylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcyclooxygenase pathway

Inferred from sequence or structural similarity. Source: UniProtKB

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 oxidative stress

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functiondioxygenase activity

Inferred from electronic annotation. Source: UniProtKB-KW

heme binding

Inferred from sequence or structural similarity. Source: UniProtKB

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 sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Ref.2
Chain17 – 603587Prostaglandin G/H synthase 2
PRO_0000023880

Regions

Domain17 – 5438EGF-like

Sites

Active site1921Proton acceptor By similarity
Active site3701For cyclooxygenase activity By similarity
Metal binding3731Iron (heme axial ligand) By similarity
Binding site1051Substrate By similarity
Binding site3401Substrate By similarity
Binding site3701Substrate By similarity
Site5151Aspirin-acetylated serine By similarity

Amino acid modifications

Modified residue5251S-nitrosocysteine By similarity
Glycosylation521N-linked (GlcNAc...) Potential
Glycosylation1291N-linked (GlcNAc...) Potential
Glycosylation3951N-linked (GlcNAc...) Potential
Glycosylation5791N-linked (GlcNAc...) Potential
Disulfide bond20 ↔ 31 By similarity
Disulfide bond21 ↔ 144 By similarity
Disulfide bond25 ↔ 41 By similarity
Disulfide bond43 ↔ 53 By similarity
Disulfide bond554 ↔ 560 By similarity

Experimental info

Sequence conflict99 – 1013RYV → GYK AA sequence Ref.2
Sequence conflict2521K → KH AA sequence Ref.2
Sequence conflict2561V → N AA sequence Ref.2
Sequence conflict5201Missing AA sequence Ref.2
Sequence conflict5281E → A AA sequence Ref.2

Sequences

Sequence LengthMass (Da)Tools
P79208 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: E27F5E0549BB1C52

FASTA60368,969
        10         20         30         40         50         60 
MLARALLLCA AVVCGAANPC CSHPCQNRGV CMSVGFDQYK CDCTRTGFYG ENCTTPEFLT 

        70         80         90        100        110        120 
RIKLLLKPTP DTVHYILTHF KGVWNIVNKI SFLRNMIMRY VLTSRSHLIE SPPTYNVHYS 

       130        140        150        160        170        180 
YKSWEAFSNL SYYTRALPPV PDDCPTPMGV KGRKELPDSK EVVKKVLLRR KFIPDPQGTN 

       190        200        210        220        230        240 
LMFAFFAQHF THQFFKTDIE RGPAFTKGKN HGVDLSHVYG ESLERQHNRR LFKDGKMKYQ 

       250        260        270        280        290        300 
MINGEMYPPT VKDTQVEMIY PPHIPEHLKF AVGQEVFGLV PGLMMYATIW LREHNRVCDV 

       310        320        330        340        350        360 
LKQEHPEWGD EQLFQTSRLI LIGETIKIVI EDYVQHLSGY HFKLKFDPEL LFNQQFQYQN 

       370        380        390        400        410        420 
RIAAEFNTLY HWHPLLPDVF QIDGQEYNYQ QFIYNNSVLL EHGVTQFVES FTRQIAGRVA 

       430        440        450        460        470        480 
GRRNLPAAVE KVSKASLDQS REMKYQSFNE YRKRFLLKPY ESFEELTGEK EMAAELEALY 

       490        500        510        520        530        540 
GDIDAMELYP ALLVEKPAPD AIFGETMVEA GAPFSLKGLM GNPICSPEYW KPSTFGGEVG 

       550        560        570        580        590        600 
FKIINTASIQ SLICSNVKGC PFTSFSVQDA HLTKTVTINA SSSHSGLDDI NPTVLLKERS 


TEL 

« Hide

References

[1]"Molecular cloning, functional expression, and selective regulation of ovine prostaglandin H synthase-2."
Zhang V., O'Sullivan M., Hussain H., Roswit W.T., Holtzman M.J.
Biochem. Biophys. Res. Commun. 227:499-506(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Purification and characterization of prostaglandin H synthase-2 from sheep placental cotyledons."
Johnson J.L., Wimsatt J., Buckel S.D., Dyer R.D., Maddipati K.R.
Arch. Biochem. Biophys. 324:26-34(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 17-52; 99-115; 183-196; 247-257; 286-306; 444-454; 473-485 AND 508-532.
Tissue: Placenta.
[3]"Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition."
Marnett L.J., Rowlinson S.W., Goodwin D.C., Kalgutkar A.S., Lanzo C.A.
J. Biol. Chem. 274:22903-22906(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AND INHIBITION BY NSAIDS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U68486 mRNA. Translation: AAC48684.1.
PIRJC5063.
RefSeqNP_001009432.1. NM_001009432.1.
UniGeneOar.642.

3D structure databases

ProteinModelPortalP79208.
SMRP79208. Positions 17-568.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP79208.
ChEMBLCHEMBL4102.

Protein family/group databases

PeroxiBase4122. OarPGHS02.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID443460.

Organism-specific databases

CTD5743.

Phylogenomic databases

HOVERGENHBG000366.

Enzyme and pathway databases

BRENDA1.14.99.1. 4472.
UniPathwayUPA00662.

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. 1 hit.
[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...

Entry information

Entry namePGH2_SHEEP
AccessionPrimary (citable) accession number: P79208
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 1, 1997
Last modified: July 9, 2014
This is version 114 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