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P79208

- PGH2_SHEEP

UniProt

P79208 - PGH2_SHEEP

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Protein

Prostaglandin G/H synthase 2

Gene
PTGS2, COX2
Organism
Ovis aries (Sheep)
Status
Reviewed - 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.1 Publication

Catalytic activityi

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

Cofactori

Binds 1 heme B (iron-protoporphyrin IX) group per subunit By similarity.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei105 – 1051Substrate By similarity
Active sitei192 – 1921Proton acceptor By similarity
Binding sitei340 – 3401Substrate By similarity
Active sitei370 – 3701For cyclooxygenase activity By similarity
Binding sitei370 – 3701Substrate By similarity
Metal bindingi373 – 3731Iron (heme axial ligand) By similarity
Sitei515 – 5151Aspirin-acetylated serine By similarity

GO - Molecular functioni

  1. dioxygenase activity Source: UniProtKB-KW
  2. heme binding Source: UniProtKB
  3. metal ion binding Source: UniProtKB-KW
  4. peroxidase activity Source: UniProtKB-KW
  5. prostaglandin-endoperoxide synthase activity Source: UniProtKB

GO - Biological processi

  1. cyclooxygenase pathway Source: UniProtKB
  2. prostaglandin biosynthetic process Source: UniProtKB
  3. regulation of blood pressure Source: UniProtKB
  4. response to oxidative stress Source: InterPro
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. 4472.
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei4122. OarPGHS02.

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
OrganismiOvis aries (Sheep)
Taxonomic identifieri9940 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis
ProteomesiUP000002356: Unplaced

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  3. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 16161 PublicationAdd
BLAST
Chaini17 – 603587Prostaglandin G/H synthase 2PRO_0000023880Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi20 ↔ 31 By similarity
Disulfide bondi21 ↔ 144 By similarity
Disulfide bondi25 ↔ 41 By similarity
Disulfide bondi43 ↔ 53 By similarity
Glycosylationi52 – 521N-linked (GlcNAc...) Reviewed prediction
Glycosylationi129 – 1291N-linked (GlcNAc...) Reviewed prediction
Glycosylationi395 – 3951N-linked (GlcNAc...) Reviewed prediction
Modified residuei525 – 5251S-nitrosocysteine By similarity
Disulfide bondi554 ↔ 560 By similarity
Glycosylationi579 – 5791N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-525 By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, S-nitrosylation

Interactioni

Subunit structurei

Homodimer By similarity.

Structurei

3D structure databases

ProteinModelPortaliP79208.
SMRiP79208. Positions 17-568.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini17 – 5438EGF-likeAdd
BLAST

Sequence similaritiesi

Contains 1 EGF-like domain.

Keywords - Domaini

Signal

Phylogenomic databases

HOVERGENiHBG000366.

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.

P79208-1 [UniParc]FASTAAdd to Basket

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MLARALLLCA AVVCGAANPC CSHPCQNRGV CMSVGFDQYK CDCTRTGFYG    50
ENCTTPEFLT RIKLLLKPTP DTVHYILTHF KGVWNIVNKI SFLRNMIMRY 100
VLTSRSHLIE SPPTYNVHYS YKSWEAFSNL SYYTRALPPV PDDCPTPMGV 150
KGRKELPDSK EVVKKVLLRR KFIPDPQGTN LMFAFFAQHF THQFFKTDIE 200
RGPAFTKGKN HGVDLSHVYG ESLERQHNRR LFKDGKMKYQ MINGEMYPPT 250
VKDTQVEMIY PPHIPEHLKF AVGQEVFGLV PGLMMYATIW LREHNRVCDV 300
LKQEHPEWGD EQLFQTSRLI LIGETIKIVI EDYVQHLSGY HFKLKFDPEL 350
LFNQQFQYQN RIAAEFNTLY HWHPLLPDVF QIDGQEYNYQ QFIYNNSVLL 400
EHGVTQFVES FTRQIAGRVA GRRNLPAAVE KVSKASLDQS REMKYQSFNE 450
YRKRFLLKPY ESFEELTGEK EMAAELEALY GDIDAMELYP ALLVEKPAPD 500
AIFGETMVEA GAPFSLKGLM GNPICSPEYW KPSTFGGEVG FKIINTASIQ 550
SLICSNVKGC PFTSFSVQDA HLTKTVTINA SSSHSGLDDI NPTVLLKERS 600
TEL 603
Length:603
Mass (Da):68,969
Last modified:May 1, 1997 - v1
Checksum:iE27F5E0549BB1C52
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti99 – 1013RYV → GYK AA sequence 1 Publication
Sequence conflicti252 – 2521K → KH AA sequence 1 Publication
Sequence conflicti256 – 2561V → N AA sequence 1 Publication
Sequence conflicti520 – 5201Missing AA sequence 1 Publication
Sequence conflicti528 – 5281E → A AA sequence 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U68486 mRNA. Translation: AAC48684.1.
PIRiJC5063.
RefSeqiNP_001009432.1. NM_001009432.1.
UniGeneiOar.642.

Genome annotation databases

GeneIDi443460.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U68486 mRNA. Translation: AAC48684.1 .
PIRi JC5063.
RefSeqi NP_001009432.1. NM_001009432.1.
UniGenei Oar.642.

3D structure databases

ProteinModelPortali P79208.
SMRi P79208. Positions 17-568.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P79208.
ChEMBLi CHEMBL4102.

Protein family/group databases

PeroxiBasei 4122. OarPGHS02.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 443460.

Organism-specific databases

CTDi 5743.

Phylogenomic databases

HOVERGENi HBG000366.

Enzyme and pathway databases

UniPathwayi UPA00662 .
BRENDAi 1.14.99.1. 4472.

Family and domain databases

Gene3Di 1.10.640.10. 1 hit.
InterProi IPR029576. COX-2.
IPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view ]
PANTHERi PTHR11903:SF8. PTHR11903:SF8. 1 hit.
Pfami PF03098. An_peroxidase. 1 hit.
[Graphical view ]
PRINTSi PR00457. ANPEROXIDASE.
SMARTi SM00181. EGF. 1 hit.
[Graphical view ]
SUPFAMi SSF48113. SSF48113. 1 hit.
PROSITEi PS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Molecular cloning, functional expression, and selective regulation of ovine prostaglandin H synthase-2."
    Zhang V., O'Sullivan M., Hussain H., Roswit W.T., Holtzman M.J.
    Biochem. Biophys. Res. Commun. 227:499-506(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Purification and characterization of prostaglandin H synthase-2 from sheep placental cotyledons."
    Johnson J.L., Wimsatt J., Buckel S.D., Dyer R.D., Maddipati K.R.
    Arch. Biochem. Biophys. 324:26-34(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 17-52; 99-115; 183-196; 247-257; 286-306; 444-454; 473-485 AND 508-532.
    Tissue: Placenta.
  3. "Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition."
    Marnett L.J., Rowlinson S.W., Goodwin D.C., Kalgutkar A.S., Lanzo C.A.
    J. Biol. Chem. 274:22903-22906(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AND INHIBITION BY NSAIDS.

Entry informationi

Entry nameiPGH2_SHEEP
AccessioniPrimary (citable) accession number: P79208
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 1, 1997
Last modified: September 3, 2014
This is version 115 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

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