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P35355 (PGH2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 141. 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length604 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

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

Expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus.

Induction

By cytokines and mitogens.

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
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processanagen

Inferred from electronic annotation. Source: Ensembl

angiogenesis

Inferred from mutant phenotype PubMed 21273371. Source: RGD

bone mineralization

Inferred from mutant phenotype PubMed 18519738. Source: MGI

brown fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

cellular response to ATP

Inferred from expression pattern PubMed 21678415. Source: RGD

cellular response to UV

Inferred from expression pattern PubMed 22306367. Source: RGD

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 21051526. Source: RGD

cyclooxygenase pathway

Inferred from sequence or structural similarity. Source: UniProtKB

decidualization

Inferred from mutant phenotype PubMed 17485303. Source: RGD

embryo implantation

Inferred from mutant phenotype PubMed 17485303. Source: RGD

hair cycle

Inferred from expression pattern PubMed 19180200. Source: RGD

inflammatory response

Inferred from mutant phenotype PubMed 17701021. Source: RGD

learning

Inferred from mutant phenotype PubMed 21701788. Source: RGD

maintenance of blood-brain barrier

Inferred from mutant phenotype PubMed 17704356. Source: RGD

memory

Inferred from mutant phenotype PubMed 18540883. Source: RGD

negative regulation of calcium ion transport

Inferred from mutant phenotype PubMed 17766482. Source: RGD

negative regulation of cell cycle

Inferred from genetic interaction PubMed 11756433. Source: RGD

negative regulation of cell proliferation

Inferred from direct assay PubMed 11756433. Source: RGD

negative regulation of smooth muscle contraction

Inferred from mutant phenotype PubMed 21051526. Source: RGD

negative regulation of synaptic transmission, dopaminergic

Inferred from mutant phenotype PubMed 18764909. Source: RGD

ovulation

Inferred from mutant phenotype PubMed 17485303. Source: RGD

positive regulation of NF-kappaB import into nucleus

Inferred from mutant phenotype PubMed 20472710. Source: RGD

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 17828456. Source: RGD

positive regulation of brown fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell death

Inferred from mutant phenotype PubMed 22306367. Source: RGD

positive regulation of cell migration involved in sprouting angiogenesis

Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 22165968. Source: RGD

positive regulation of fever generation

Inferred from direct assay PubMed 19940926. Source: BHF-UCL

positive regulation of fibroblast growth factor production

Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL

positive regulation of nitric oxide biosynthetic process

Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL

positive regulation of platelet-derived growth factor production

Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL

positive regulation of smooth muscle cell proliferation

Inferred from mutant phenotype PubMed 17645304. Source: RGD

positive regulation of smooth muscle contraction

Inferred from mutant phenotype PubMed 18480553. Source: RGD

positive regulation of synaptic plasticity

Inferred from mutant phenotype PubMed 18540883. Source: RGD

positive regulation of synaptic transmission, glutamatergic

Inferred from mutant phenotype PubMed 18764909. Source: RGD

positive regulation of transforming growth factor beta production

Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL

positive regulation of vasoconstriction

Inferred from mutant phenotype PubMed 18456673. Source: RGD

positive regulation vascular endothelial growth factor production

Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL

prostaglandin biosynthetic process

Inferred from mutant phenotype PubMed 17673564. Source: RGD

regulation of blood pressure

Inferred from sequence or structural similarity. Source: UniProtKB

response to cytokine

Inferred from mutant phenotype PubMed 18383135. Source: RGD

response to drug

Inferred from expression pattern PubMed 17883899. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 18310519. Source: RGD

response to fatty acid

Inferred from expression pattern PubMed 16983392. Source: RGD

response to fructose

Inferred from expression pattern PubMed 17883899. Source: RGD

response to glucocorticoid

Inferred from expression pattern PubMed 18657281. Source: RGD

response to lipopolysaccharide

Inferred from mutant phenotype PubMed 17766482. Source: RGD

response to lithium ion

Inferred from expression pattern PubMed 12232777. Source: RGD

response to manganese ion

Inferred from expression pattern PubMed 17827730. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 18769055. Source: RGD

response to organic substance

Inferred from expression pattern PubMed 18373278. Source: RGD

response to organonitrogen compound

Inferred from expression pattern PubMed 11211925. Source: RGD

response to oxidative stress

Inferred from electronic annotation. Source: InterPro

response to radiation

Inferred from expression pattern PubMed 18606213. Source: RGD

response to tumor necrosis factor

Inferred from expression pattern PubMed 17704356. Source: RGD

response to vitamin D

Inferred from expression pattern PubMed 18348265. Source: RGD

sensory perception of pain

Inferred from mutant phenotype PubMed 21362433. Source: RGD

   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

protein complex

Inferred from direct assay PubMed 16479074. Source: RGD

   Molecular_functionheme binding

Inferred from sequence or structural similarity. Source: UniProtKB

lipid binding

Inferred from mutant phenotype PubMed 17245358. Source: RGD

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen

Inferred from direct assay Ref.3. Source: RGD

peroxidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

prostaglandin-endoperoxide synthase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 16479074. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Ref.6
Chain18 – 604587Prostaglandin G/H synthase 2
PRO_0000023879

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

Experimental info

Sequence conflict11 – 133ALA → CPG Ref.4
Sequence conflict11 – 133ALA → CPG Ref.5
Sequence conflict581E → R Ref.4
Sequence conflict581E → R Ref.5
Sequence conflict661L → P Ref.4
Sequence conflict661L → P Ref.5
Sequence conflict96 – 983NSI → IQS Ref.4
Sequence conflict96 – 983NSI → IQS Ref.5
Sequence conflict3391S → R Ref.4
Sequence conflict3391S → R Ref.5
Sequence conflict3441K → Q Ref.4
Sequence conflict3441K → Q Ref.5
Sequence conflict3501E → D Ref.4
Sequence conflict3501E → D Ref.5
Sequence conflict3681N → K Ref.4
Sequence conflict3681N → K Ref.5
Sequence conflict5731P → A Ref.4
Sequence conflict5731P → A Ref.5

Sequences

Sequence LengthMass (Da)Tools
P35355 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: 98E418825D98FF0C

FASTA60469,164
        10         20         30         40         50         60 
MLFRAVLLCA ALALSHAANP CCSNPCQNRG ECMSIGFDQY KCDCTRTGFY GENCTTPEFL 

        70         80         90        100        110        120 
TRIKLLLKPT PNTVHYILTH FKGVWNIVNN IPFLRNSIMR YVLTSRSHLI DSPPTYNVHY 

       130        140        150        160        170        180 
GYKSWEAFSN LSYYTRALPP VADDCPTPMG VKGNKELPDS KEVLEKVLLR REFIPDPQGT 

       190        200        210        220        230        240 
NMMFAFFAQH FTHQFFKTDQ KRGPGFTRGL GHGVDLNHVY GETLDRQHKL RLFQDGKLKY 

       250        260        270        280        290        300 
QVIGGEVYPP TVKDTQVDMI YPPHVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD 

       310        320        330        340        350        360 
ILKQEHPEWD DERLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE LLFNQQFQYQ 

       370        380        390        400        410        420 
NRIASEFNTL YHWHPLLPDT FNIEDQEYTF KQFLYNNSIL LEHGLAHFVE SFTRQIAGRV 

       430        440        450        460        470        480 
AGGRNVPIAV QAVAKASIDQ SREMKYQSLN EYRKRFSLKP YTSFEELTGE KEMAAELKAL 

       490        500        510        520        530        540 
YHDIDAMELY PALLVEKPRP DAIFGETMVE LGAPFSLKGL MGNPICSPQY WKPSTFGGEV 

       550        560        570        580        590        600 
GFRIINTASI QSLICNNVKG CPFASFNVQD PQPTKTATIN ASASHSRLDD INPTVLIKRR 


STEL 

« Hide

References

[1]"Cloning and expression of rat prostaglandin endoperoxide synthase (cyclooxygenase)-2 cDNA."
Kennedy B.P., Chan C.C., Culp S.A., Cromlish W.A.
Biochem. Biophys. Res. Commun. 197:494-500(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids."
Yamagata K., Andreasson K.I., Kaufmann W.E., Barnes C.A., Worley P.F.
Neuron 11:371-386(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Cloning and characterization of a growth factor-inducible cyclooxygenase gene from rat intestinal epithelial cells."
Dubois R.N., Tsujii M., Bishop P., Awad J.A., Makita K., Lanahan A.
Am. J. Physiol. 266:G822-G827(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Wistar.
Tissue: Intestine.
[4]"Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression."
Feng L., Sun W., Xia Y., Tang W.W., Chanmugam P., Soyoola E., Wilson C.B., Hwang D.
Arch. Biochem. Biophys. 307:361-368(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Fischer 344.
[5]"Immediate-early MEK-1-dependent stabilization of rat smooth muscle cell cyclooxygenase-2 mRNA by Galpha(q)-coupled receptor signaling."
Xu K., Robida A.M., Murphy T.J.
J. Biol. Chem. 275:23012-23019(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]"Purification and characterization of a novel, distinct isoform of prostaglandin endoperoxide synthase induced by human chorionic gonadotropin in granulosa cells of rat preovulatory follicles."
Sirois J., Richards J.S.
J. Biol. Chem. 267:6382-6388(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 18-43.
[7]"Cyclooxygenases: structural, cellular, and molecular biology."
Smith W.L., DeWitt D.L., Garavito R.M.
Annu. Rev. Biochem. 69:145-182(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION; TISSUE SPECIFICITY AND INHIBITION BY NSAIDS.
[8]"Aspirin, cyclooxygenase inhibition and colorectal cancer."
Sostres C., Gargallo C.J., Lanas A.
World J. Gastrointest. Pharmacol. Ther. 5:40-49(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL CANCER.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L25925 mRNA. Translation: AAA16477.1.
U04300 mRNA. Translation: AAA20246.1.
U03389 mRNA. Translation: AAA03466.1.
S67722 mRNA. Translation: AAB29401.1.
AF233596 mRNA. Translation: AAF36986.1.
PIRJC2030.
RefSeqNP_058928.3. NM_017232.3.
UniGeneRn.217585.
Rn.44369.

3D structure databases

ProteinModelPortalP35355.
SMRP35355. Positions 18-569.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248163. 1 interaction.

Chemistry

BindingDBP35355.
ChEMBLCHEMBL2095157.

Protein family/group databases

PeroxiBase3975. RnoPGHS02-A.

PTM databases

PhosphoSiteP35355.

Proteomic databases

PaxDbP35355.
PRIDEP35355.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000003567; ENSRNOP00000003567; ENSRNOG00000002525.
GeneID29527.
KEGGrno:29527.
UCSCRGD:620349. rat.

Organism-specific databases

CTD5743.
RGD620349. Ptgs2.

Phylogenomic databases

eggNOGNOG39991.
GeneTreeENSGT00390000010743.
HOGENOMHOG000013149.
HOVERGENHBG000366.
InParanoidP35355.
KOK11987.
OMAICNNVKG.
OrthoDBEOG7RFTHC.
PhylomeDBP35355.
TreeFamTF329675.

Enzyme and pathway databases

UniPathwayUPA00662.

Gene expression databases

GenevestigatorP35355.

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. 1 hit.
[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...

Other

NextBio609492.
PROP35355.

Entry information

Entry namePGH2_RAT
AccessionPrimary (citable) accession number: P35355
Secondary accession number(s): Q64379, Q925V4
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 11, 2014
This is version 141 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