Gene/Proteome Database (LMPD)

LMPD ID
LMP012603
Gene ID
Species
Rattus norvegicus (Rat)
Gene Name
prostaglandin-endoperoxide synthase 2
Gene Symbol
Synonyms
Cox2; COX-2;
Alternate Names
prostaglandin G/H synthase 2; PGHS-2; PHS II; PGH synthase 2; cyclooxygenase 2; cyclooxygenase-2; prostaglandin H2 synthase 2;
Chromosome
13
Map Location
13q21
EC Number
1.14.99.1
Summary
catalyzes the conversion of arachidonic acid products to prostaglandin; may play a role in response to endotoxic shock; may a role in long term potentiation [RGD, Feb 2006]
Orthologs

Proteins

prostaglandin G/H synthase 2 precursor
Refseq ID NP_058928
Protein GI 148747270
UniProt ID P35355
mRNA ID NM_017232
Length 604
MLFRAVLLCAALALSHAANPCCSNPCQNRGECMSIGFDQYKCDCTRTGFYGENCTTPEFLTRIKLLLKPTPNTVHYILTHFKGVWNIVNNIPFLRNSIMRYVLTSRSHLIDSPPTYNVHYGYKSWEAFSNLSYYTRALPPVADDCPTPMGVKGNKELPDSKEVLEKVLLRREFIPDPQGTNMMFAFFAQHFTHQFFKTDQKRGPGFTRGLGHGVDLNHVYGETLDRQHKLRLFQDGKLKYQVIGGEVYPPTVKDTQVDMIYPPHVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCDILKQEHPEWDDERLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNQQFQYQNRIASEFNTLYHWHPLLPDTFNIEDQEYTFKQFLYNNSILLEHGLAHFVESFTRQIAGRVAGGRNVPIAVQAVAKASIDQSREMKYQSLNEYRKRFSLKPYTSFEELTGEKEMAAELKALYHDIDAMELYPALLVEKPRPDAIFGETMVELGAPFSLKGLMGNPICSPQYWKPSTFGGEVGFRIINTASIQSLICNNVKGCPFASFNVQDPQPTKTATINASASHSRLDDINPTVLIKRRSTEL
sig_peptide: 1..17 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1800 peptide sequence: MLFRAVLLCAALALSHA mat_peptide: 18..604 product: Prostaglandin G/H synthase 2 experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P35355.1) calculated_mol_wt: 67382 peptide sequence: ANPCCSNPCQNRGECMSIGFDQYKCDCTRTGFYGENCTTPEFLTRIKLLLKPTPNTVHYILTHFKGVWNIVNNIPFLRNSIMRYVLTSRSHLIDSPPTYNVHYGYKSWEAFSNLSYYTRALPPVADDCPTPMGVKGNKELPDSKEVLEKVLLRREFIPDPQGTNMMFAFFAQHFTHQFFKTDQKRGPGFTRGLGHGVDLNHVYGETLDRQHKLRLFQDGKLKYQVIGGEVYPPTVKDTQVDMIYPPHVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCDILKQEHPEWDDERLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNQQFQYQNRIASEFNTLYHWHPLLPDTFNIEDQEYTFKQFLYNNSILLEHGLAHFVESFTRQIAGRVAGGRNVPIAVQAVAKASIDQSREMKYQSLNEYRKRFSLKPYTSFEELTGEKEMAAELKALYHDIDAMELYPALLVEKPRPDAIFGETMVELGAPFSLKGLMGNPICSPQYWKPSTFGGEVGFRIINTASIQSLICNNVKGCPFASFNVQDPQPTKTATINASASHSRLDDINPTVLIKRRSTEL

Gene Information

Entrez Gene ID
Gene Name
prostaglandin-endoperoxide synthase 2
Gene Symbol
Species
Rattus norvegicus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005737 ISS:UniProtKB C cytoplasm
GO:0005783 IEA:UniProtKB-KW C endoplasmic reticulum
GO:0016020 IEA:UniProtKB-KW C membrane
GO:0043005 IEA:Ensembl C neuron projection
GO:0005634 ISS:UniProtKB C nucleus
GO:0043234 IDA:RGD C protein complex
GO:0020037 ISS:UniProtKB F heme binding
GO:0008289 IMP:RGD F lipid binding
GO:0046872 IEA:UniProtKB-KW F metal ion binding
GO:0016702 IDA:RGD 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 ISS:UniProtKB F prostaglandin-endoperoxide synthase activity
GO:0042640 IEA:Ensembl P anagen
GO:0001525 IMP:RGD P angiogenesis
GO:0030282 IMP:MGI P bone mineralization
GO:0050873 IEA:Ensembl P brown fat cell differentiation
GO:0071318 IEP:RGD P cellular response to ATP
GO:0034644 IEP:RGD P cellular response to UV
GO:0071456 IEA:Ensembl P cellular response to hypoxia
GO:0071260 IEP:RGD P cellular response to mechanical stimulus
GO:0019371 ISS:UniProtKB P cyclooxygenase pathway
GO:0046697 IMP:RGD P decidualization
GO:0007566 IMP:RGD P embryo implantation
GO:0042633 IEP:RGD P hair cycle
GO:0006954 IMP:RGD P inflammatory response
GO:0007612 IMP:RGD P learning
GO:0035633 IMP:RGD P maintenance of blood-brain barrier
GO:0007613 IMP:RGD P memory
GO:0051926 IMP:RGD P negative regulation of calcium ion transport
GO:0045786 IGI:RGD P negative regulation of cell cycle
GO:0008285 IDA:RGD P negative regulation of cell proliferation
GO:0045986 IMP:RGD P negative regulation of smooth muscle contraction
GO:0032227 IMP:RGD P negative regulation of synaptic transmission, dopaminergic
GO:0030728 IMP:RGD P ovulation
GO:0042346 IMP:RGD P positive regulation of NF-kappaB import into nucleus
GO:0043065 IMP:RGD P positive regulation of apoptotic process
GO:0090336 IEA:Ensembl P positive regulation of brown fat cell differentiation
GO:0010942 IMP:RGD P positive regulation of cell death
GO:0090050 IMP:BHF-UCL P positive regulation of cell migration involved in sprouting angiogenesis
GO:0008284 IMP:RGD P positive regulation of cell proliferation
GO:0031622 IDA:BHF-UCL P positive regulation of fever generation
GO:0090271 IMP:BHF-UCL P positive regulation of fibroblast growth factor production
GO:0045429 IMP:BHF-UCL P positive regulation of nitric oxide biosynthetic process
GO:0090362 IMP:BHF-UCL P positive regulation of platelet-derived growth factor production
GO:0048661 IMP:RGD P positive regulation of smooth muscle cell proliferation
GO:0045987 IMP:RGD P positive regulation of smooth muscle contraction
GO:0031915 IMP:RGD P positive regulation of synaptic plasticity
GO:0051968 IMP:RGD P positive regulation of synaptic transmission, glutamatergic
GO:0071636 IMP:BHF-UCL P positive regulation of transforming growth factor beta production
GO:0045907 IMP:RGD P positive regulation of vasoconstriction
GO:0010575 IMP:BHF-UCL P positive regulation vascular endothelial growth factor production
GO:0001516 IMP:RGD P prostaglandin biosynthetic process
GO:0008217 ISS:UniProtKB P regulation of blood pressure
GO:0034097 IMP:RGD P response to cytokine
GO:0042493 IEP:RGD P response to drug
GO:0032355 IEP:RGD P response to estradiol
GO:0070542 IEP:RGD P response to fatty acid
GO:0009750 IEP:RGD P response to fructose
GO:0051384 IEP:RGD P response to glucocorticoid
GO:0032496 IMP:RGD P response to lipopolysaccharide
GO:0010226 IEP:RGD P response to lithium ion
GO:0010042 IEP:RGD P response to manganese ion
GO:0014070 IEP:RGD P response to organic cyclic compound
GO:0010033 IEP:RGD P response to organic substance
GO:0010243 IEP:RGD P response to organonitrogen compound
GO:0006979 IEA:InterPro P response to oxidative stress
GO:0009314 IEP:RGD P response to radiation
GO:0034612 IEP:RGD P response to tumor necrosis factor
GO:0033280 IEP:RGD P response to vitamin D
GO:0019233 IMP:RGD P sensory perception of pain

KEGG Pathway Links

KEGG Pathway ID Description
ko00590 Arachidonic acid metabolism
rno00590 Arachidonic acid metabolism
ko05204 Chemical carcinogenesis
rno05204 Chemical carcinogenesis
ko05140 Leishmaniasis
rno05140 Leishmaniasis
rno01100 Metabolic pathways
ko05206 MicroRNAs in cancer
rno05206 MicroRNAs in cancer
rno04064 NF-kappa B signaling pathway
ko04913 Ovarian steroidogenesis
rno04913 Ovarian steroidogenesis
ko04921 Oxytocin signaling pathway
rno04921 Oxytocin signaling pathway
rno05200 Pathways in cancer
ko04723 Retrograde endocannabinoid signaling
rno04723 Retrograde endocannabinoid signaling
rno04726 Serotonergic synapse
ko05222 Small cell lung cancer
rno05222 Small cell lung cancer
ko04668 TNF signaling pathway
rno04668 TNF signaling pathway
ko04370 VEGF signaling pathway
rno04370 VEGF signaling pathway

REACTOME Pathway Links

REACTOME Pathway ID Description
5953493 Arachidonic acid metabolism
5953298 Defective AMN causes hereditary megaloblastic anemia 1
5953308 Defective BTD causes biotidinase deficiency
5953307 Defective CD320 causes methylmalonic aciduria
5953299 Defective CUBN causes hereditary megaloblastic anemia 1
5953296 Defective GIF causes intrinsic factor deficiency
5953310 Defective HLCS causes multiple carboxylase deficiency
5953297 Defective LMBRD1 causes methylmalonic aciduria and homocystinuria type cblF
5953305 Defective MMAA causes methylmalonic aciduria type cblA
5953302 Defective MMAB causes methylmalonic aciduria type cblB
5953304 Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC
5953303 Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD
5953301 Defective MTR causes methylmalonic aciduria and homocystinuria type cblG
5953300 Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE
5953306 Defective MUT causes methylmalonic aciduria mut type
5953293 Defective TCN2 causes hereditary megaloblastic anemia
5953309 Defects in biotin (Btn) metabolism
5953294 Defects in cobalamin (B12) metabolism
5953295 Defects in vitamin and cofactor metabolism
5953253 Disease
5953250 Metabolism
5953289 Metabolism of lipids and lipoproteins
5953292 Metabolism of vitamins and cofactors
5953291 Metabolism of water-soluble vitamins and cofactors
5953489 Nicotinamide salvaging
5953490 Nicotinate metabolism
5954557 Synthesis of 15-eicosatetraenoic acid derivatives
5953492 Synthesis of Prostaglandins (PG) and Thromboxanes (TX)

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_RAT
UniProt ID
Species
Rat

Comments

Comment Type Description
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 (By similarity)
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
Tissue Specificity Expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus.

Identical and Related Proteins

Unique RefSeq proteins for LMP012603 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
148747270 RefSeq NP_058928 604 prostaglandin G/H synthase 2 precursor

Identical Sequences to LMP012603 proteins

Reference Database Accession Length Protein Name
GI:148747270 GenBank ABP06333.1 604 Sequence 30 from patent US 7179627
GI:148747270 GenBank EDM09586.1 604 prostaglandin-endoperoxide synthase 2, isoform CRA_a [Rattus norvegicus]
GI:148747270 GenBank ADA08483.1 604 Sequence 30 from patent US 7601816
GI:148747270 PRF - 604 growth factor-inducible cyclooxygenase [Rattus norvegicus]

Related Sequences to LMP012603 proteins

Reference Database Accession Length Protein Name
GI:148747270 GenBank AAA20246.1 604 mitogen inducible cyclooxygenase [Rattus norvegicus]
GI:148747270 PRF - 604 growth factor-inducible cyclooxygenase [Rattus norvegicus]
GI:148747270 SwissProt P35355.1 604 RecName: Full=Prostaglandin G/H synthase 2; AltName: Full=Cyclooxygenase-2; Short=COX-2; AltName: Full=PHS II; AltName: Full=Prostaglandin H2 synthase 2; Short=PGH synthase 2; Short=PGHS-2; AltName: Full=Prostaglandin-endoperoxide synthase 2; Flags: Precursor [Rattus norvegicus]