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O02768 (PGH2_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 115. 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:COX-2, COX2
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

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. 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 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.

Tissue specificity

Highest expression in kidney and urinary bladder.

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.

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
Reference proteome
Gene Ontology (GO)
   Biological_processanagen

Inferred from electronic annotation. Source: Ensembl

brown fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cyclooxygenase pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of brown fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of fever generation

Inferred from electronic annotation. Source: Ensembl

prostaglandin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of blood pressure

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

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

neuron projection

Inferred from electronic annotation. Source: Ensembl

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 – 1717 By similarity
Chain18 – 604587Prostaglandin G/H synthase 2
PRO_0000023878

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
O02768 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: C52F9F5BC1F493D7

FASTA60469,007
        10         20         30         40         50         60 
MLARALLLCA AVALSHAANP CCSNPCQNRG VCMTMGFDQY KCDCTRTGFY GENCSTPEFL 

        70         80         90        100        110        120 
TRIKLLLKPT PDTVHYILTH FKGVWNIVNS IPFLRNSIMK YVLTSRSHMI DSPPTYNVHY 

       130        140        150        160        170        180 
NYKSWEAFSN LSYYTRALPP VADDCPTPMG VKGKKELPDS KDVVEKLLLR RKFIPDPQGT 

       190        200        210        220        230        240 
NMMFAFFAQH FTHQFFKTDL KRGPAFTKGL GHGVDLNHIY GETLDRQHKL RLFKDGKMKY 

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

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

       370        380        390        400        410        420 
NRIAAEFNTL YHWHPLLPDT FQIDDQQYNY QQFLYNNSIL LEHGLTQFVE SFTRQIAGRV 

       430        440        450        460        470        480 
AGGRNVPPAV QKVAKASIDQ SRQMKYQSLN EYRKRFLLKP YESFEELTGE KEMAAELEAL 

       490        500        510        520        530        540 
YGDIDAVELY PALLVERPRP DAIFGESMVE MGAPFSLKGL MGNPICSPNY WKPSTFGGEV 

       550        560        570        580        590        600 
GFKIVNTASI QSLICNNVKG CPFTSFNVPD PQLTKTVTIN ASASHSRLED INPTVLLKGR 


STEL 

« Hide

References

[1]"Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells."
Guan Y., Chang M., Cho W., Zhang Y., Redha R., Davis L., Chang S., Dubois R.N., Hao C.M., Breyer M.
Am. J. Physiol. 273:F18-F26(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: New Zealand white.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U97696 mRNA. Translation: AAB71222.1.
RefSeqNP_001075857.1. NM_001082388.1.
UniGeneOcu.2173.

3D structure databases

ProteinModelPortalO02768.
SMRO02768. Positions 18-568.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9986.ENSOCUP00000014415.

Chemistry

BindingDBO02768.
ChEMBLCHEMBL1293198.

Protein family/group databases

PeroxiBase4130. OcuPGHS02.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSOCUT00000016770; ENSOCUP00000014415; ENSOCUG00000016771.
GeneID100009248.

Organism-specific databases

CTD5743.

Phylogenomic databases

eggNOGNOG39991.
GeneTreeENSGT00390000010743.
HOGENOMHOG000013149.
HOVERGENHBG000366.
OMAICNNVKG.
OrthoDBEOG7RFTHC.
TreeFamTF329675.

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...

Entry information

Entry namePGH2_RABIT
AccessionPrimary (citable) accession number: O02768
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 1, 1997
Last modified: May 14, 2014
This is version 115 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