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O62698 (PGH2_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. 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
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length604 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. 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 By similarity.

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-526 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 By similarity
Chain18 – 604587Prostaglandin G/H synthase 2
PRO_0000023872

Regions

Domain18 – 5538EGF-like

Sites

Active site1931Proton acceptor By similarity
Active site3711For cyclooxygenase activity By similarity
Metal binding3741Iron (heme axial ligand) By similarity
Binding site1061Substrate By similarity
Binding site3411Substrate By similarity
Binding site3711Substrate By similarity
Site5161Aspirin-acetylated serine By similarity

Amino acid modifications

Modified residue5261S-nitrosocysteine By similarity
Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation1301N-linked (GlcNAc...) Potential
Glycosylation3961N-linked (GlcNAc...) Potential
Glycosylation5801N-linked (GlcNAc...) Potential
Disulfide bond21 ↔ 32 By similarity
Disulfide bond22 ↔ 145 By similarity
Disulfide bond26 ↔ 42 By similarity
Disulfide bond44 ↔ 54 By similarity
Disulfide bond555 ↔ 561 By similarity

Experimental info

Sequence conflict61L → M in AAC28562. Ref.1
Sequence conflict1111E → D in AAC05592. Ref.2
Sequence conflict4581V → L in AAC28562. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O62698 [UniParc].

Last modified December 15, 1998. Version 2.
Checksum: 16EA2E51D0A01A45

FASTA60469,163
        10         20         30         40         50         60 
MLARALLLCA AVALSGAANP CCSHPCQNRG VCMSVGFDQY KCDCTRTGFY GENCTTPEFL 

        70         80         90        100        110        120 
TRIKLLLKPT PNTVHYILTH FKGVWNIVNK ISFLRNMIMR YVLTSRSHLI ESPPTYNVHY 

       130        140        150        160        170        180 
SYKSWEAFSN LSYYTRALPP VPDDCPTPMG VKGRKELPDS KEVVKKVLLR RKFIPDPQGT 

       190        200        210        220        230        240 
NLMFAFFAQH FTHQFFKTDF ERGPAFTKGK NHGVDLSHIY GESLERQHKL RLFKDGKMKY 

       250        260        270        280        290        300 
QMINGEMYPP TVKDTQVEMI YPPHVPEHLK FAVGQEVFGL VPGLMMYATI WLREHNRVCD 

       310        320        330        340        350        360 
VLKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE LLFNQQFQYQ 

       370        380        390        400        410        420 
NRIAAEFNTL YHWHPLLPDV FQIDGQEYNY QQFIYNNSVL LEHGLTQFVE SFTRQRAGRV 

       430        440        450        460        470        480 
AGGRNLPVAV EKVSKASIDQ SREMKYQSFN EYRKRFLVKP YESFEELTGE KEMAAELEAL 

       490        500        510        520        530        540 
YGDIDAMEFY PALLVEKPRP DAIFGETMVE AGAPFSLKGL MGNPICSPEY WKPSTFGGEV 

       550        560        570        580        590        600 
GFKIINTASI QSLICSNVKG CPFTSFSVQD THLTKTVTIN ASSSHSGLDD INPTVLLKER 


STEL 

« Hide

References

[1]"Molecular characterization of bovine prostaglandin G/H synthase-2 and regulation in uterine stromal cells."
Liu J., Antaya M., Goff A.K., Boerboom D., Silversides D.W., Lussier J.G., Sirois J.
Biol. Reprod. 64:983-991(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cellular mechanisms involved during oxytocin-induced prostaglandin F2alpha production in endometrial epithelial cells in vitro: role of cyclooxygenase-2."
Asselin E., Drolet P., Fortier M.A.
Endocrinology 138:4798-4805(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 105-253.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF031698 mRNA. Translation: AAC04702.1.
AF031699 Genomic DNA. Translation: AAC28562.1.
AF004944 mRNA. Translation: AAC05592.1.
RefSeqNP_776870.1. NM_174445.2.
UniGeneBt.15758.

3D structure databases

ProteinModelPortalO62698.
SMRO62698. Positions 18-569.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000018774.

Chemistry

BindingDBO62698.
ChEMBLCHEMBL3331.

Protein family/group databases

PeroxiBase3330. BtPGHS02.

Proteomic databases

PRIDEO62698.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID282023.
KEGGbta:282023.

Organism-specific databases

CTD5743.

Phylogenomic databases

eggNOGNOG39991.
HOGENOMHOG000013149.
HOVERGENHBG000366.
InParanoidO62698.
KOK11987.

Enzyme and pathway databases

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. 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

NextBio20805887.

Entry information

Entry namePGH2_BOVIN
AccessionPrimary (citable) accession number: O62698
Secondary accession number(s): O46517, O62665
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: December 15, 1998
Last modified: July 9, 2014
This is version 123 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