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O62725 (PGH2_NEOVI) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 100. 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
OrganismNeovison vison (American mink) (Mustela vison)
Taxonomic identifier452646 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaMustelidaeMustelinaeNeovison

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_0000023877

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

Sequences

Sequence LengthMass (Da)Tools
O62725 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: E28D19F47CD926F8

FASTA60468,950
        10         20         30         40         50         60 
MLARAGLLCA SLSPPHAANP CCSNPCQNQG VCMSIGFDQY MCDCSRTGFY GENCSTPEFL 

        70         80         90        100        110        120 
TRVKLLLKPT PNTVHYILTH FKGVWNIVNK IPFLADVIMK YVRTSRSHCI EPPPTYNVHY 

       130        140        150        160        170        180 
AYKSWEAFSN LSYYTRALPP VADDCPTPMG VKGKKELPDS KEIVEKFLLR RKFIPDPQGT 

       190        200        210        220        230        240 
NMMFAFFAQH FTHQFFKTDH KRGPGFTKGL GHGVDLSHVY GETLDRQHKL RLFKDGKMKY 

       250        260        270        280        290        300 
QVIDGEVYPP TVKDTQVEMI YPPHVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD 

       310        320        330        340        350        360 
VLKQEQGEWD DERLFRRSRL ILIGETIKIV IEDYVRHLSG YHFSLKFDPE LLFNQQFQYQ 

       370        380        390        400        410        420 
NRIAAEFNTL YHWHPLLPDT LQIDDQEYNF QQFVYNNSIL LEHGLTQFGE SFSRQIAGRV 

       430        440        450        460        470        480 
AGGRNVPAAV QQEQRASIDQ SRQMKYQSLN EYRKRFSVKP YASFEELTGE KEMAGELKAL 

       490        500        510        520        530        540 
YQDIDAMELY PALLVEKPRP DAIFGETMVE IGAPFSLKGL MGNPICSPDY WKPSHFGGEV 

       550        560        570        580        590        600 
GFKIINTASI QSLICNNVKG CPFTAFSVQD PQLTKTVTIN GSSSHSGLDD INPTVLLKER 


STEL 

« Hide

References

[1]"Cloning, developmental expression, and immunohistochemistry of cyclooxygenase 2 in the endometrium during embryo implantation and gestation in the mink (Mustela vison)."
Song J.H., Sirois J., Houde A., Murphy B.D.
Endocrinology 139:3629-3636(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Uterus.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF047841 mRNA. Translation: AAC05637.1.

3D structure databases

ProteinModelPortalO62725.
SMRO62725. Positions 18-569.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

PeroxiBase4136. MvPGHS02.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG000366.

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. 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_NEOVI
AccessionPrimary (citable) accession number: O62725
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: August 1, 1998
Last modified: May 14, 2014
This is version 100 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