Gene/Proteome Database (LMPD)

LMPD ID
LMP000816
Gene ID
19225
Species
Mus musculus (Mouse)
Gene Name
prostaglandin-endoperoxide synthase 2
Gene Symbol
Ptgs2
Synonyms
COX2; Cox-2; PGHS-2; PHS-2; Pghs2; TIS10
Alternate Names
prostaglandin G/H synthase 2; PES-2; PHS II; gripghs; PGH synthase 2; cyclooxygenase 2; cyclooxygenase-2; prostaglandin H2 synthase 2; glucocorticoid-regulated inflammatory cyclooxygenase; macrophage activation-associated marker protein P71/73
Chromosome
1
Map Location
1 H1|1 63.84 cM
EC Number
1.14.99.1

Proteins

prostaglandin G/H synthase 2 precursor
Refseq ID NP_035328
Protein GI 31981525
UniProt ID Q05769
mRNA ID NM_011198
Length 604
RefSeq Status PROVISIONAL
MLFRAVLLCAALGLSQAANPCCSNPCQNRGECMSTGFDQYKCDCTRTGFYGENCTTPEFLTRIKLLLKPTPNTVHYILTHFKGVWNIVNNIPFLRSLIMKYVLTSRSYLIDSPPTYNVHYGYKSWEAFSNLSYYTRALPPVADDCPTPMGVKGNKELPDSKEVLEKVLLRREFIPDPQGSNMMFAFFAQHFTHQFFKTDHKRGPGFTRGLGHGVDLNHIYGETLDRQHKLRLFKDGKLKYQVIGGEVYPPTVKDTQVEMIYPPHIPENLQFAVGQEVFGLVPGLMMYATIWLREHNRVCDILKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNQQFQYQNRIASEFNTLYHWHPLLPDTFNIEDQEYSFKQFLYNNSILLEHGLTQFVESFTRQIAGRVAGGRNVPIAVQAVAKASIDQSREMKYQSLNEYRKRFSLKPYTSFEELTGEKEMAAELKALYSDIDVMELYPALLVEKPRPDAIFGETMVELGAPFSLKGLMGNPICSPQYWKPSTFGGEVGFKIINTASIQSLICNNVKGCPFTSFNVQDPQPTKTATINASASHSRLDDINPTVLIKRRSTEL
sig_peptide: 1..17 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1777 peptide sequence: MLFRAVLLCAALGLSQA mat_peptide: 18..604 product: Prostaglandin G/H synthase 2 experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (Q05769.1) calculated_mol_wt: 67254 peptide sequence: ANPCCSNPCQNRGECMSTGFDQYKCDCTRTGFYGENCTTPEFLTRIKLLLKPTPNTVHYILTHFKGVWNIVNNIPFLRSLIMKYVLTSRSYLIDSPPTYNVHYGYKSWEAFSNLSYYTRALPPVADDCPTPMGVKGNKELPDSKEVLEKVLLRREFIPDPQGSNMMFAFFAQHFTHQFFKTDHKRGPGFTRGLGHGVDLNHIYGETLDRQHKLRLFKDGKLKYQVIGGEVYPPTVKDTQVEMIYPPHIPENLQFAVGQEVFGLVPGLMMYATIWLREHNRVCDILKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNQQFQYQNRIASEFNTLYHWHPLLPDTFNIEDQEYSFKQFLYNNSILLEHGLTQFVESFTRQIAGRVAGGRNVPIAVQAVAKASIDQSREMKYQSLNEYRKRFSLKPYTSFEELTGEKEMAAELKALYSDIDVMELYPALLVEKPRPDAIFGETMVELGAPFSLKGLMGNPICSPQYWKPSTFGGEVGFKIINTASIQSLICNNVKGCPFTSFNVQDPQPTKTATINASASHSRLDDINPTVLIKRRSTEL

Gene Information

Entrez Gene ID
19225
Gene Name
prostaglandin-endoperoxide synthase 2
Gene Symbol
Ptgs2
Species
Mus musculus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005737 IDA:MGI C cytoplasm
GO:0005783 IEA:UniProtKB-KW C endoplasmic reticulum
GO:0016020 IEA:UniProtKB-KW C membrane
GO:0043005 IDA:MGI C neuron projection
GO:0043234 IEA:Ensembl C protein complex
GO:0020037 IDA:UniProtKB F heme binding
GO:0008289 IEA:Ensembl F lipid binding
GO:0046872 IEA:UniProtKB-KW F metal ion binding
GO:0016702 IEA:Ensembl F oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
GO:0004601 IEA:UniProtKB-KW F peroxidase activity
GO:0004666 IDA:UniProtKB F prostaglandin-endoperoxide synthase activity
GO:0042803 IPI:UniProtKB F protein homodimerization activity
GO:0042640 IMP:MGI P anagen
GO:0001525 IEA:Ensembl P angiogenesis
GO:0030282 ISO:MGI P bone mineralization
GO:0050873 IMP:BHF-UCL P brown fat cell differentiation
GO:0071318 IEA:Ensembl P cellular response to ATP
GO:0034644 IEA:Ensembl P cellular response to UV
GO:0071456 IEA:Ensembl P cellular response to hypoxia
GO:0071260 IEA:Ensembl P cellular response to mechanical stimulus
GO:0019371 IDA:UniProtKB P cyclooxygenase pathway
GO:0046697 IEA:Ensembl P decidualization
GO:0007566 IEA:Ensembl P embryo implantation
GO:0006954 IEA:Ensembl P inflammatory response
GO:0030216 NAS:UniProtKB P keratinocyte differentiation
GO:0007612 IEA:Ensembl P learning
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 IMP:BHF-UCL P positive regulation of brown fat cell differentiation
GO:0090050 IEA:Ensembl P positive regulation of cell migration involved in sprouting angiogenesis
GO:0031622 IDA:BHF-UCL P positive regulation of fever generation
GO:0090271 IEA:Ensembl P positive regulation of fibroblast growth factor production
GO:0045429 IEA:Ensembl P positive regulation of nitric oxide biosynthetic process
GO:0090362 IEA:Ensembl P positive regulation of platelet-derived growth factor production
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 IEA:Ensembl P positive regulation of transforming growth factor beta production
GO:0045907 IEA:Ensembl P positive regulation of vasoconstriction
GO:0010575 IEA:Ensembl P positive regulation vascular endothelial growth factor production
GO:0001516 IDA:UniProtKB P prostaglandin biosynthetic process
GO:0008217 IMP:MGI P regulation of blood pressure
GO:0042127 IGI:MGI P regulation of cell proliferation
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

KEGG Pathway Links

KEGG Pathway ID Description
mmu05206 MicroRNAs in cancer
mmu04913 Ovarian steroidogenesis
mmu04921 Oxytocin signaling pathway
mmu04668 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
Protein Entry
PGH2_MOUSE
UniProt ID
Q05769
Species
Mouse

Comments

Comment Type Description
Catalytic Activity Arachidonate + AH(2) + 2 O(2) = prostaglandin H(2) + A + H(2)O. {ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:20810665, ECO:0000269|PubMed:21489986}.
Cofactor Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:8967954}; Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit. {ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:8967954};
Developmental Stage During colonic wound repair, highly up- regulated (more than 1600-fold) in the mesenchyme of the wound bed 2 days after injury as compared to uninjured mucosa. Further increase in expression is observed at day 4 following injury (close to 2200-fold). Down-regulated at day 6 (only 93-fold increase as compared to uninjured mucosa). {ECO:0000269|PubMed:22465430}.
Disruption Phenotype Mutant mice exhibit defects in colonic mucosal wound repair. {ECO:0000269|PubMed:22465430}.
Enzyme Regulation Inhibited by the nonsteroidal anti-inflammatory drugs aspirin, naproxen, diclofenac, meclofenamic acid, indomethacin and their analogs. {ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20810665}.
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. {ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:20810665, ECO:0000269|PubMed:21489986, ECO:0000269|PubMed:22465430}.
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 (By similarity). {ECO:0000250}.
Similarity Belongs to the prostaglandin G/H synthase family. {ECO:0000305}.
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. {ECO:0000269|PubMed:10811226, ECO:0000269|PubMed:12925531, ECO:0000269|PubMed:20463020, ECO:0000269|PubMed:21489986, ECO:0000269|PubMed:8967954}.
Tissue Specificity Following colon injury, expressed in the wound bed mesenchyme during the first phase of repair, probably by colonic mesenchymal stem cells (at protein level). {ECO:0000269|PubMed:22465430}.

Identical and Related Proteins

Unique RefSeq proteins for LMP000816 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
31981525 RefSeq NP_035328 604 prostaglandin G/H synthase 2 precursor

Identical Sequences to LMP000816 proteins

Reference Database Accession Length Protein Name
GI:31981525 GenBank EDL39487.1 604 prostaglandin-endoperoxide synthase 2 [Mus musculus]
GI:31981525 GenBank ADA08482.1 604 Sequence 29 from patent US 7601816
GI:31981525 PDB 4FM5 604 Chain A, X-Ray Structure Of Des-Methylflurbiprofen Bound To Murine Cox-2
GI:31981525 PDB 4FM5 604 Chain B, X-Ray Structure Of Des-Methylflurbiprofen Bound To Murine Cox-2
GI:31981525 PDB 4FM5 604 Chain C, X-Ray Structure Of Des-Methylflurbiprofen Bound To Murine Cox-2
GI:31981525 PDB 4FM5 604 Chain D, X-Ray Structure Of Des-Methylflurbiprofen Bound To Murine Cox-2

Related Sequences to LMP000816 proteins

Reference Database Accession Length Protein Name
GI:31981525 DBBJ BAE26032.1 604 unnamed protein product [Mus musculus]
GI:31981525 GenBank AAA39918.1 604 prostaglandin synthase [Mus musculus]
GI:31981525 GenBank AAA39924.1 604 prostaglandin synthase [Mus musculus]
GI:31981525 GenBank AAB23883.1 604 PGHS-B=prostaglandin G/H synthase homolog [Mus sp.]
GI:31981525 GenBank ACW56524.1 604 Sequence 8 from patent US 7588758
GI:31981525 PDB 3QH0 610 Chain B, X-Ray Crystal Structure Of Palmitic Acid Bound To The Cyclooxygenase Channel Of Cyclooxygenase-2