Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Prostaglandin G/H synthase 2

Gene

PTGS2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

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

Pathway: prostaglandin biosynthesis

This protein is involved in the pathway prostaglandin biosynthesis, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway prostaglandin biosynthesis and in Lipid metabolism.

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

GO - Biological processi

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. 908.
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei3330. BtPGHS02.

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:COX2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717By similarityAdd
BLAST
Chaini18 – 604587Prostaglandin G/H synthase 2PRO_0000023872Add
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

PRIDEiO62698.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000018774.

Structurei

3D structure databases

ProteinModelPortaliO62698.
SMRiO62698. 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.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiO62698.
KOiK11987.

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. 2 hits.
[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.

O62698-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLARALLLCA AVALSGAANP CCSHPCQNRG VCMSVGFDQY KCDCTRTGFY
60 70 80 90 100
GENCTTPEFL TRIKLLLKPT PNTVHYILTH FKGVWNIVNK ISFLRNMIMR
110 120 130 140 150
YVLTSRSHLI ESPPTYNVHY SYKSWEAFSN LSYYTRALPP VPDDCPTPMG
160 170 180 190 200
VKGRKELPDS KEVVKKVLLR RKFIPDPQGT NLMFAFFAQH FTHQFFKTDF
210 220 230 240 250
ERGPAFTKGK NHGVDLSHIY GESLERQHKL RLFKDGKMKY QMINGEMYPP
260 270 280 290 300
TVKDTQVEMI YPPHVPEHLK FAVGQEVFGL VPGLMMYATI WLREHNRVCD
310 320 330 340 350
VLKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE
360 370 380 390 400
LLFNQQFQYQ NRIAAEFNTL YHWHPLLPDV FQIDGQEYNY QQFIYNNSVL
410 420 430 440 450
LEHGLTQFVE SFTRQRAGRV AGGRNLPVAV EKVSKASIDQ SREMKYQSFN
460 470 480 490 500
EYRKRFLVKP YESFEELTGE KEMAAELEAL YGDIDAMEFY PALLVEKPRP
510 520 530 540 550
DAIFGETMVE AGAPFSLKGL MGNPICSPEY WKPSTFGGEV GFKIINTASI
560 570 580 590 600
QSLICSNVKG CPFTSFSVQD THLTKTVTIN ASSSHSGLDD INPTVLLKER

STEL
Length:604
Mass (Da):69,163
Last modified:December 15, 1998 - v2
Checksum:i16EA2E51D0A01A45
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61L → M in AAC28562 (PubMed:11207216).Curated
Sequence conflicti111 – 1111E → D in AAC05592 (PubMed:9348208).Curated
Sequence conflicti458 – 4581V → L in AAC28562 (PubMed:11207216).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF031698 mRNA. Translation: AAC04702.1.
AF031699 Genomic DNA. Translation: AAC28562.1.
AF004944 mRNA. Translation: AAC05592.1.
RefSeqiNP_776870.1. NM_174445.2.
UniGeneiBt.15758.

Genome annotation databases

GeneIDi282023.
KEGGibta:282023.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF031698 mRNA. Translation: AAC04702.1.
AF031699 Genomic DNA. Translation: AAC28562.1.
AF004944 mRNA. Translation: AAC05592.1.
RefSeqiNP_776870.1. NM_174445.2.
UniGeneiBt.15758.

3D structure databases

ProteinModelPortaliO62698.
SMRiO62698. Positions 18-569.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000018774.

Chemistry

BindingDBiO62698.
ChEMBLiCHEMBL2096674.

Protein family/group databases

PeroxiBasei3330. BtPGHS02.

Proteomic databases

PRIDEiO62698.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi282023.
KEGGibta:282023.

Organism-specific databases

CTDi5743.

Phylogenomic databases

eggNOGiNOG39991.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiO62698.
KOiK11987.

Enzyme and pathway databases

UniPathwayiUPA00662.
BRENDAi1.14.99.1. 908.

Miscellaneous databases

NextBioi20805887.
PROiO62698.

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. 2 hits.
[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. "Molecular characterization of bovine prostaglandin G/H synthase-2 and regulation in uterine stromal cells."
    Liu J., Antaya M., Goff A.K., Boerboom D., Silversides D.W., Lussier J.G., Sirois J.
    Biol. Reprod. 64:983-991(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Cellular mechanisms involved during oxytocin-induced prostaglandin F2alpha production in endometrial epithelial cells in vitro: role of cyclooxygenase-2."
    Asselin E., Drolet P., Fortier M.A.
    Endocrinology 138:4798-4805(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 105-253.

Entry informationi

Entry nameiPGH2_BOVIN
AccessioniPrimary (citable) accession number: O62698
Secondary accession number(s): O46517, O62665
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: December 15, 1998
Last modified: April 29, 2015
This is version 131 of the entry and version 2 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, 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.