Gene/Proteome Database (LMPD)

LMPD ID
LMP000761
Gene ID
5743
Species
Homo sapiens (Human)
Gene Name
prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)
Gene Symbol
PTGS2
Synonyms
COX-2; COX2; GRIPGHS; PGG/HS; PGHS-2; PHS-2; hCox-2
Chromosome
1
Map Location
1q25.2-q25.3
EC Number
1.14.99.1
Summary
Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009]
Orthologs
View orthologs and multiple alignments for PTGS2

Proteins

prostaglandin G/H synthase 2 precursor
Refseq ID NP_000954
Protein GI 4506265
UniProt ID P35354
mRNA ID NM_000963
Length 604
MLARALLLCAVLALSHTANPCCSHPCQNRGVCMSVGFDQYKCDCTRTGFYGENCSTPEFLTRIKLFLKPTPNTVHYILTHFKGFWNVVNNIPFLRNAIMSYVLTSRSHLIDSPPTYNADYGYKSWEAFSNLSYYTRALPPVPDDCPTPLGVKGKKQLPDSNEIVEKLLLRRKFIPDPQGSNMMFAFFAQHFTHQFFKTDHKRGPAFTNGLGHGVDLNHIYGETLARQRKLRLFKDGKMKYQIIDGEMYPPTVKDTQAEMIYPPQVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCDVLKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNKQFQYQNRIAAEFNTLYHWHPLLPDTFQIHDQKYNYQQFIYNNSILLEHGITQFVESFTRQIAGRVAGGRNVPPAVQKVSQASIDQSRQMKYQSFNEYRKRFMLKPYESFEELTGEKEMSAELEALYGDIDAVELYPALLVEKPRPDAIFGETMVEVGAPFSLKGLMGNVICSPAYWKPSTFGGEVGFQIINTASIQSLICNNVKGCPFTSFSVPDPELIKTVTINASSSRSGLDDINPTVLLKERSTEL
sig_peptide: 1..23 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2372 peptide sequence: MLARALLLCAVLALSHTANPCCS

Gene Information

Entrez Gene ID
5743
Gene Name
prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)
Gene Symbol
PTGS2
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0005789 TAS:Reactome C endoplasmic reticulum membrane
GO:0043005 IDA:MGI C neuron projection
GO:0005634 ISS:UniProtKB C nucleus
GO:0043234 IEA:Ensembl C protein complex
GO:0050473 TAS:Reactome F arachidonate 15-lipoxygenase activity
GO:0019899 IPI:UniProtKB F enzyme binding
GO:0020037 ISS:UniProtKB F heme binding
GO:0008289 IEA:Ensembl F lipid binding
GO:0046872 IEA:UniProtKB-KW F metal ion binding
GO:0004601 NAS:UniProtKB F peroxidase activity
GO:0004666 IDA:UniProtKB F prostaglandin-endoperoxide synthase activity
GO:0042640 IEA:Ensembl P anagen
GO:0001525 IEA:Ensembl P angiogenesis
GO:0019369 TAS:Reactome P arachidonic acid metabolic process
GO:0030282 IEA:Ensembl P bone mineralization
GO:0050873 IEA:Ensembl P brown fat cell differentiation
GO:0006928 TAS:ProtInc P cellular component movement
GO:0071318 IEA:Ensembl P cellular response to ATP
GO:0034644 IEA:Ensembl P cellular response to UV
GO:0071456 IEP:UniProtKB P cellular response to hypoxia
GO:0071260 IEA:Ensembl P cellular response to mechanical stimulus
GO:0019371 IDA:BHF-UCL P cyclooxygenase pathway
GO:0046697 IEA:Ensembl P decidualization
GO:0007566 IEA:Ensembl P embryo implantation
GO:0006954 IEA:Ensembl P inflammatory response
GO:0007612 IEA:Ensembl P learning
GO:0019372 TAS:Reactome P lipoxygenase pathway
GO:0035633 IEA:Ensembl P maintenance of blood-brain barrier
GO:0007613 IEA:Ensembl P memory
GO:0051926 IEA:Ensembl P negative regulation of calcium ion transport
GO:0045786 IEA:Ensembl P negative regulation of cell cycle
GO:0008285 IEA:Ensembl P negative regulation of cell proliferation
GO:0045986 IEA:Ensembl P negative regulation of smooth muscle contraction
GO:0032227 IEA:Ensembl P negative regulation of synaptic transmission, dopaminergic
GO:0030728 IEA:Ensembl P ovulation
GO:0042346 IEA:Ensembl P positive regulation of NF-kappaB import into nucleus
GO:0043065 IEA:Ensembl P positive regulation of apoptotic process
GO:0090336 ISS:BHF-UCL P positive regulation of brown fat cell differentiation
GO:0090050 ISS:BHF-UCL P positive regulation of cell migration involved in sprouting angiogenesis
GO:0031622 ISS:BHF-UCL P positive regulation of fever generation
GO:0090271 ISS:BHF-UCL P positive regulation of fibroblast growth factor production
GO:0045429 ISS:BHF-UCL P positive regulation of nitric oxide biosynthetic process
GO:0090362 ISS:BHF-UCL P positive regulation of platelet-derived growth factor production
GO:0031394 NAS:BHF-UCL P positive regulation of prostaglandin biosynthetic process
GO:0048661 IEA:Ensembl P positive regulation of smooth muscle cell proliferation
GO:0045987 IEA:Ensembl P positive regulation of smooth muscle contraction
GO:0031915 IEA:Ensembl P positive regulation of synaptic plasticity
GO:0051968 IEA:Ensembl P positive regulation of synaptic transmission, glutamatergic
GO:0071636 ISS:BHF-UCL P positive regulation of transforming growth factor beta production
GO:0045907 IEA:Ensembl P positive regulation of vasoconstriction
GO:0010575 ISS:BHF-UCL P positive regulation vascular endothelial growth factor production
GO:0001516 ISS:UniProtKB P prostaglandin biosynthetic process
GO:0006693 TAS:ProtInc P prostaglandin metabolic process
GO:0008217 ISS:UniProtKB P regulation of blood pressure
GO:0050727 NAS:UniProtKB P regulation of inflammatory response
GO:0042493 IEA:Ensembl P response to drug
GO:0032355 IEA:Ensembl P response to estradiol
GO:0070542 IEA:Ensembl P response to fatty acid
GO:0009750 IEA:Ensembl P response to fructose
GO:0051384 IEA:Ensembl P response to glucocorticoid
GO:0032496 IEA:Ensembl P response to lipopolysaccharide
GO:0010226 IEA:Ensembl P response to lithium ion
GO:0010042 IEA:Ensembl P response to manganese ion
GO:0006979 IEA:InterPro P response to oxidative stress
GO:0034612 IEA:Ensembl P response to tumor necrosis factor
GO:0033280 IEA:Ensembl P response to vitamin D
GO:0019233 IEA:Ensembl P sensory perception of pain
GO:0044281 TAS:Reactome P small molecule metabolic process

KEGG Pathway Links

KEGG Pathway ID Description
hsa05206 MicroRNAs in cancer
hsa04913 Ovarian steroidogenesis
hsa04921 Oxytocin signaling pathway
hsa04668 TNF signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR000742 Epidermal growth factor-like domain
IPR019791 Haem peroxidase, animal
IPR010255 Haem_peroxidase
IPR029576 Prostaglandin G/H synthase 2

UniProt Annotations

Entry Information

Gene Name
prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)
Protein Entry
PGH2_HUMAN
UniProt ID
P35354
Species
Human

Comments

Comment Type Description
Biophysicochemical Properties Kinetic parameters: KM=16.2 uM for arachidonate (in absence of sodium nitroprusside NO donor) ; KM=17.0 uM for arachidonate (in presence of sodium nitroprusside NO donor) ; Vmax=81.3 nmol/min/mg enzyme (in absence of sodium nitroprusside NO donor) ; Vmax=132 nmol/min/mg enzyme (in absence of sodium nitroprusside NO donor) ;
Catalytic Activity Arachidonate + AH(2) + 2 O(2) = prostaglandin H(2) + A + H(2)O
Cofactor Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence= ; Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit. ;
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
Induction By cytokines and mitogens.
Miscellaneous 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.
Miscellaneous 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.
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.
Pathway Lipid metabolism; prostaglandin biosynthesis.
Ptm S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S- nitrosylation may take place on different Cys residues in addition to Cys-526
Similarity Belongs to the prostaglandin G/H synthase family
Similarity Contains 1 EGF-like domain. {ECO:0000255|PROSITE- ProRule:PRU00076}.
Subcellular Location Microsome membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein.
Subunit Homodimer
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PTGS2ID509ch1q31.html";
Web Resource Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ptgs2/";
Web Resource Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/ptgs2/";

Identical and Related Proteins

Unique RefSeq proteins for LMP000761 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
4506265 RefSeq NP_000954 604 prostaglandin G/H synthase 2 precursor

Identical Sequences to LMP000761 proteins

Reference Database Accession Length Protein Name

Related Sequences to LMP000761 proteins

Reference Database Accession Length Protein Name