P70682 (PGH2_CAVPO) Reviewed, UniProtKB/Swiss-Prot
Last modified May 14, 2014. Version 111. History...
Names and origin
|Protein names||Recommended name:|
Prostaglandin G/H synthase 2
Prostaglandin H2 synthase 2
Short name=PGH synthase 2
Prostaglandin-endoperoxide synthase 2
|Organism||Cavia porcellus (Guinea pig) [Reference proteome]|
|Taxonomic identifier||10141 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Hystricognathi › Caviidae › Cavia|
|Sequence length||604 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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.
Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.
Binds 1 heme B (iron-protoporphyrin IX) group per subunit By similarity.
Homodimer By similarity.
S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526 By similarity.
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.
Belongs to the prostaglandin G/H synthase family.
Contains 1 EGF-like domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 17||17||By similarity|
|Chain||18 – 604||587||Prostaglandin G/H synthase 2||PRO_0000023873|
|Domain||18 – 55||38||EGF-like|
|Active site||193||1||Proton acceptor By similarity|
|Active site||371||1||For cyclooxygenase activity By similarity|
|Metal binding||374||1||Iron (heme axial ligand) By similarity|
|Binding site||106||1||Substrate By similarity|
|Binding site||341||1||Substrate By similarity|
|Binding site||371||1||Substrate By similarity|
|Site||516||1||Aspirin-acetylated serine By similarity|
Amino acid modifications
|Modified residue||526||1||S-nitrosocysteine By similarity|
|Glycosylation||53||1||N-linked (GlcNAc...) Potential|
|Glycosylation||130||1||N-linked (GlcNAc...) Potential|
|Glycosylation||396||1||N-linked (GlcNAc...) Potential|
|Glycosylation||580||1||N-linked (GlcNAc...) Potential|
|Disulfide bond||21 ↔ 32||By similarity|
|Disulfide bond||22 ↔ 145||By similarity|
|Disulfide bond||26 ↔ 42||By similarity|
|Disulfide bond||44 ↔ 54||By similarity|
|Disulfide bond||555 ↔ 561||By similarity|
|||"Cloning of guinea pig cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase complementary deoxyribonucleic acids: steroid-modulated gene expression correlates to prostaglandin F2 alpha secretion in cultured endometrial cells."|
Bracken K.E., Elger W., Jantke I., Nanninga A., Gellersen B.
Endocrinology 138:237-247(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|Y07896 mRNA. Translation: CAA69204.1.|
|RefSeq||NP_001166478.1. NM_001173007.1. |
3D structure databases
|SMR||P70682. Positions 18-568. |
Protein-protein interaction databases
Protein family/group databases
|PeroxiBase||4137. CpoPGHS02. |
Protocols and materials databases
Genome annotation databases
Enzyme and pathway databases
Family and domain databases
|Gene3D||1.10.640.10. 1 hit. |
|InterPro||IPR000742. EG-like_dom. |
|Pfam||PF03098. An_peroxidase. 1 hit. |
|PRINTS||PR00457. ANPEROXIDASE. |
|SUPFAM||SSF48113. SSF48113. 1 hit. |
|PROSITE||PS50026. EGF_3. 1 hit. |
PS50292. PEROXIDASE_3. 1 hit.
|Accession||Primary (citable) accession number: P70682|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|