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Protein

Prostaglandin G/H synthase 2

Gene

Ptgs2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.

Cofactori

heme bBy similarityNote: Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.By similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei106 – 1061SubstrateBy similarity
Active sitei193 – 1931Proton acceptorPROSITE-ProRule annotation
Binding sitei341 – 3411SubstrateBy similarity
Active sitei371 – 3711For cyclooxygenase activityBy similarity
Binding sitei371 – 3711SubstrateBy similarity
Metal bindingi374 – 3741Iron (heme axial ligand)PROSITE-ProRule annotation
Sitei516 – 5161Aspirin-acetylated serineBy similarity

GO - Molecular functioni

  1. heme binding Source: UniProtKB
  2. lipid binding Source: RGD
  3. metal ion binding Source: UniProtKB-KW
  4. oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: RGD
  5. peroxidase activity Source: UniProtKB-KW
  6. prostaglandin-endoperoxide synthase activity Source: UniProtKB

GO - Biological processi

  1. angiogenesis Source: RGD
  2. bone mineralization Source: MGI
  3. brown fat cell differentiation Source: Ensembl
  4. cellular response to ATP Source: RGD
  5. cellular response to hypoxia Source: Ensembl
  6. cellular response to mechanical stimulus Source: RGD
  7. cellular response to UV Source: RGD
  8. cyclooxygenase pathway Source: UniProtKB
  9. decidualization Source: RGD
  10. embryo implantation Source: RGD
  11. hair cycle Source: RGD
  12. inflammatory response Source: RGD
  13. learning Source: RGD
  14. maintenance of blood-brain barrier Source: RGD
  15. memory Source: RGD
  16. negative regulation of calcium ion transport Source: RGD
  17. negative regulation of cell cycle Source: RGD
  18. negative regulation of cell proliferation Source: RGD
  19. negative regulation of smooth muscle contraction Source: RGD
  20. negative regulation of synaptic transmission, dopaminergic Source: RGD
  21. ovulation Source: RGD
  22. positive regulation of apoptotic process Source: RGD
  23. positive regulation of brown fat cell differentiation Source: Ensembl
  24. positive regulation of cell death Source: RGD
  25. positive regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
  26. positive regulation of cell proliferation Source: RGD
  27. positive regulation of fever generation Source: BHF-UCL
  28. positive regulation of fibroblast growth factor production Source: BHF-UCL
  29. positive regulation of NF-kappaB import into nucleus Source: RGD
  30. positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
  31. positive regulation of platelet-derived growth factor production Source: BHF-UCL
  32. positive regulation of smooth muscle cell proliferation Source: RGD
  33. positive regulation of smooth muscle contraction Source: RGD
  34. positive regulation of synaptic plasticity Source: RGD
  35. positive regulation of synaptic transmission, glutamatergic Source: RGD
  36. positive regulation of transforming growth factor beta production Source: BHF-UCL
  37. positive regulation of vasoconstriction Source: RGD
  38. positive regulation vascular endothelial growth factor production Source: BHF-UCL
  39. prostaglandin biosynthetic process Source: RGD
  40. regulation of blood pressure Source: UniProtKB
  41. response to cytokine Source: RGD
  42. response to drug Source: RGD
  43. response to estradiol Source: RGD
  44. response to fatty acid Source: RGD
  45. response to fructose Source: RGD
  46. response to glucocorticoid Source: RGD
  47. response to lipopolysaccharide Source: RGD
  48. response to lithium ion Source: RGD
  49. response to manganese ion Source: RGD
  50. response to organic cyclic compound Source: RGD
  51. response to organic substance Source: RGD
  52. response to organonitrogen compound Source: RGD
  53. response to oxidative stress Source: InterPro
  54. response to radiation Source: RGD
  55. response to tumor necrosis factor Source: RGD
  56. response to vitamin D Source: RGD
  57. sensory perception of pain Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase, Peroxidase

Keywords - Biological processi

Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.99.1. 5301.
ReactomeiREACT_283791. Nicotinamide salvaging.
REACT_320384. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_347479. Synthesis of 15-eicosatetraenoic acid derivatives.
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei3975. RnoPGHS02-A.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Ptgs2
Synonyms:Cox-2, Cox2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 13

Organism-specific databases

RGDi620349. Ptgs2.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  3. neuron projection Source: Ensembl
  4. nucleus Source: UniProtKB
  5. protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 17171 PublicationAdd
BLAST
Chaini18 – 604587Prostaglandin G/H synthase 2PRO_0000023879Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi21 ↔ 32By similarity
Disulfide bondi22 ↔ 145By similarity
Disulfide bondi26 ↔ 42By similarity
Disulfide bondi44 ↔ 54By similarity
Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis
Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence Analysis
Glycosylationi396 – 3961N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi555 ↔ 561By similarity
Glycosylationi580 – 5801N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, S-nitrosylation

Proteomic databases

PaxDbiP35355.
PRIDEiP35355.

PTM databases

PhosphoSiteiP35355.

Expressioni

Tissue specificityi

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

Inductioni

By cytokines and mitogens.

Gene expression databases

GenevestigatoriP35355.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi248163. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliP35355.
SMRiP35355. Positions 18-569.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 5538EGF-likePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the prostaglandin G/H synthase family.Curated
Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG39991.
GeneTreeiENSGT00390000010743.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiP35355.
KOiK11987.
OMAiICNNVKG.
OrthoDBiEOG7RFTHC.
PhylomeDBiP35355.
TreeFamiTF329675.

Family and domain databases

Gene3Di1.10.640.10. 1 hit.
InterProiIPR029576. COX-2.
IPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view]
PANTHERiPTHR11903:SF8. PTHR11903:SF8. 1 hit.
PfamiPF03098. An_peroxidase. 1 hit.
[Graphical view]
PRINTSiPR00457. ANPEROXIDASE.
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
SUPFAMiSSF48113. SSF48113. 1 hit.
PROSITEiPS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P35355-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLFRAVLLCA ALALSHAANP CCSNPCQNRG ECMSIGFDQY KCDCTRTGFY
60 70 80 90 100
GENCTTPEFL TRIKLLLKPT PNTVHYILTH FKGVWNIVNN IPFLRNSIMR
110 120 130 140 150
YVLTSRSHLI DSPPTYNVHY GYKSWEAFSN LSYYTRALPP VADDCPTPMG
160 170 180 190 200
VKGNKELPDS KEVLEKVLLR REFIPDPQGT NMMFAFFAQH FTHQFFKTDQ
210 220 230 240 250
KRGPGFTRGL GHGVDLNHVY GETLDRQHKL RLFQDGKLKY QVIGGEVYPP
260 270 280 290 300
TVKDTQVDMI YPPHVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD
310 320 330 340 350
ILKQEHPEWD DERLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE
360 370 380 390 400
LLFNQQFQYQ NRIASEFNTL YHWHPLLPDT FNIEDQEYTF KQFLYNNSIL
410 420 430 440 450
LEHGLAHFVE SFTRQIAGRV AGGRNVPIAV QAVAKASIDQ SREMKYQSLN
460 470 480 490 500
EYRKRFSLKP YTSFEELTGE KEMAAELKAL YHDIDAMELY PALLVEKPRP
510 520 530 540 550
DAIFGETMVE LGAPFSLKGL MGNPICSPQY WKPSTFGGEV GFRIINTASI
560 570 580 590 600
QSLICNNVKG CPFASFNVQD PQPTKTATIN ASASHSRLDD INPTVLIKRR

STEL
Length:604
Mass (Da):69,164
Last modified:May 31, 1994 - v1
Checksum:i98E418825D98FF0C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti11 – 133ALA → CPG (PubMed:8274023).Curated
Sequence conflicti11 – 133ALA → CPG (PubMed:10816563).Curated
Sequence conflicti58 – 581E → R (PubMed:8274023).Curated
Sequence conflicti58 – 581E → R (PubMed:10816563).Curated
Sequence conflicti66 – 661L → P (PubMed:8274023).Curated
Sequence conflicti66 – 661L → P (PubMed:10816563).Curated
Sequence conflicti96 – 983NSI → IQS (PubMed:8274023).Curated
Sequence conflicti96 – 983NSI → IQS (PubMed:10816563).Curated
Sequence conflicti339 – 3391S → R (PubMed:8274023).Curated
Sequence conflicti339 – 3391S → R (PubMed:10816563).Curated
Sequence conflicti344 – 3441K → Q (PubMed:8274023).Curated
Sequence conflicti344 – 3441K → Q (PubMed:10816563).Curated
Sequence conflicti350 – 3501E → D (PubMed:8274023).Curated
Sequence conflicti350 – 3501E → D (PubMed:10816563).Curated
Sequence conflicti368 – 3681N → K (PubMed:8274023).Curated
Sequence conflicti368 – 3681N → K (PubMed:10816563).Curated
Sequence conflicti573 – 5731P → A (PubMed:8274023).Curated
Sequence conflicti573 – 5731P → A (PubMed:10816563).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiJC2030.
RefSeqiNP_058928.3. NM_017232.3.
UniGeneiRn.217585.
Rn.44369.

Genome annotation databases

EnsembliENSRNOT00000003567; ENSRNOP00000003567; ENSRNOG00000002525.
GeneIDi29527.
KEGGirno:29527.
UCSCiRGD:620349. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiJC2030.
RefSeqiNP_058928.3. NM_017232.3.
UniGeneiRn.217585.
Rn.44369.

3D structure databases

ProteinModelPortaliP35355.
SMRiP35355. Positions 18-569.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248163. 2 interactions.

Chemistry

BindingDBiP35355.
ChEMBLiCHEMBL2977.

Protein family/group databases

PeroxiBasei3975. RnoPGHS02-A.

PTM databases

PhosphoSiteiP35355.

Proteomic databases

PaxDbiP35355.
PRIDEiP35355.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000003567; ENSRNOP00000003567; ENSRNOG00000002525.
GeneIDi29527.
KEGGirno:29527.
UCSCiRGD:620349. rat.

Organism-specific databases

CTDi5743.
RGDi620349. Ptgs2.

Phylogenomic databases

eggNOGiNOG39991.
GeneTreeiENSGT00390000010743.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiP35355.
KOiK11987.
OMAiICNNVKG.
OrthoDBiEOG7RFTHC.
PhylomeDBiP35355.
TreeFamiTF329675.

Enzyme and pathway databases

UniPathwayiUPA00662.
BRENDAi1.14.99.1. 5301.
ReactomeiREACT_283791. Nicotinamide salvaging.
REACT_320384. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_347479. Synthesis of 15-eicosatetraenoic acid derivatives.

Miscellaneous databases

NextBioi609492.
PROiP35355.

Gene expression databases

GenevestigatoriP35355.

Family and domain databases

Gene3Di1.10.640.10. 1 hit.
InterProiIPR029576. COX-2.
IPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view]
PANTHERiPTHR11903:SF8. PTHR11903:SF8. 1 hit.
PfamiPF03098. An_peroxidase. 1 hit.
[Graphical view]
PRINTSiPR00457. ANPEROXIDASE.
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
SUPFAMiSSF48113. SSF48113. 1 hit.
PROSITEiPS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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(1992) [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(1992) [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(1993) [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(1992) [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(1999) [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(1991) [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(1999) [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(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL CANCER.

Entry informationi

Entry nameiPGH2_RAT
AccessioniPrimary (citable) accession number: P35355
Secondary accession number(s): Q64379, Q925V4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 31, 1994
Last sequence update: May 31, 1994
Last modified: March 31, 2015
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.