PTGS2

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

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.

Catalytic activityⁱ

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

Cofactorⁱ

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

Pathwayⁱ: prostaglandin biosynthesis

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

Sites

Feature key	Position(s)	DescriptionActions	Length
Binding siteⁱ	106	SubstrateBy similarity	1
Active siteⁱ	193	Proton acceptorPROSITE-ProRule annotation	1
Binding siteⁱ	341	SubstrateBy similarity	1
Active siteⁱ	371	For cyclooxygenase activityBy similarity	1
Metal bindingⁱ	374	Iron (heme axial ligand)PROSITE-ProRule annotation	1
Siteⁱ	516	Aspirin-acetylated serineBy similarity	1

GO - Molecular functionⁱ

dioxygenase activity Source: UniProtKB-KW
enzyme binding Source: Ensembl
heme binding Source: UniProtKB
metal ion binding Source: UniProtKB-KW
peroxidase activity Source: UniProtKB-KW
prostaglandin-endoperoxide synthase activity Source: UniProtKB
protein homodimerization activity Source: Ensembl

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

brown fat cell differentiation Source: Ensembl
cellular response to fluid shear stress Source: Ensembl
cellular response to hypoxia Source: Ensembl
cellular response to non-ionic osmotic stress Source: Ensembl
cyclooxygenase pathway Source: UniProtKB
decidualization Source: Ensembl
embryo implantation Source: Ensembl
inflammatory response Source: InterPro
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress Source: Ensembl
positive regulation of brown fat cell differentiation Source: Ensembl
positive regulation of fever generation Source: Ensembl
positive regulation of peptidyl-serine phosphorylation Source: Ensembl
positive regulation of prostaglandin biosynthetic process Source: Ensembl
prostaglandin biosynthetic process Source: UniProtKB
regulation of blood pressure Source: UniProtKB
regulation of cell proliferation Source: Ensembl
response to oxidative stress Source: InterPro

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Dioxygenase, Oxidoreductase, Peroxidase
Biological process	Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism
Ligand	Heme, Iron, Metal-binding

Enzyme and pathway databases

UniPathwayⁱ	UPA00662

UniPathwayⁱ

UPA00662

Protein family/group databases

PeroxiBaseⁱ	4123 EcabPGHS02

PeroxiBaseⁱ

4123 EcabPGHS02

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
Organismⁱ	Equus caballus (Horse)
Taxonomic identifierⁱ	9796 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Laurasiatheria › Perissodactyla › Equidae › Equus › Equus
Proteomesⁱ	UP000002281 Componentⁱ: Chromosome 5

Organism-specific databases

VGNCⁱ	VGNC:21997 PTGS2

VGNCⁱ

VGNC:21997 PTGS2

Keywords - Cellular componentⁱ

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 17	By similarityAdd BLAST		17
ChainⁱPRO_0000023874	18 – 604	Prostaglandin G/H synthase 2Add BLAST		587

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Disulfide bondⁱ	21 ↔ 32	By similarity
Disulfide bondⁱ	22 ↔ 145	By similarity
Disulfide bondⁱ	26 ↔ 42	By similarity
Disulfide bondⁱ	44 ↔ 54	By similarity
Glycosylationⁱ	53	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	130	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	396	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	555 ↔ 561	By similarity
Glycosylationⁱ	580	N-linked (GlcNAc...) asparagineSequence analysis	1

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

PaxDbⁱ	O19183

PaxDbⁱ

O19183

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSECAG00000017181

Bgeeⁱ

ENSECAG00000017181

Interactionⁱ

Subunit structureⁱ

Homodimer.By similarity

GO - Molecular functionⁱ

enzyme binding Source: Ensembl
protein homodimerization activity Source: Ensembl

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

STRINGⁱ	9796.ENSECAP00000015107

STRINGⁱ

9796.ENSECAP00000015107

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	O19183
SMRⁱ	O19183
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	18 – 55	EGF-likePROSITE-ProRule annotationAdd BLAST		38

Sequence similaritiesⁱ

Belongs to the prostaglandin G/H synthase family.Curated

Keywords - Domainⁱ

Signal

Phylogenomic databases

eggNOGⁱ	KOG2408 Eukaryota ENOG410XPZ3 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000010743
HOGENOMⁱ	HOG000013149
HOVERGENⁱ	HBG000366
InParanoidⁱ	O19183
KEGG Orthology (KO) More...KOⁱ	K11987
OMAⁱ	CNNVKGC
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G03CD
TreeFamⁱ	TF329675

Family and domain databases

Gene3Dⁱ	1.10.640.10, 1 hit
InterProⁱ	View protein in InterPro IPR029576 COX-2 IPR000742 EGF-like_dom IPR010255 Haem_peroxidase IPR019791 Haem_peroxidase_animal IPR037120 Haem_peroxidase_sf
PANTHERⁱ	PTHR11903:SF8 PTHR11903:SF8, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF03098 An_peroxidase, 2 hits PF00008 EGF, 1 hit
PRINTSⁱ	PR00457 ANPEROXIDASE
SUPFAMⁱ	SSF48113 SSF48113, 1 hit
PROSITEⁱ	View protein in PROSITE PS50026 EGF_3, 1 hit PS50292 PEROXIDASE_3, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

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

O19183-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MLARALLLCV ALALGHAANP CCSNPCQNRG VCMSVGFDQY QCDCTRTGFY 
        60         70         80         90        100
GENCSTPEFL TRIKLFLKPT PNTVHYILTH FKGVWNIVNS FPFLRNAVMK 
       110        120        130        140        150
YVLVSRSHLI ESPPTYNAQY GYKSWESFSN LSYYTRALPP VADGCPTPMG 
       160        170        180        190        200
VKGKKELPDS KEIVEKFLLR RKFIPDPQGT NMMFAFFAQH FTHQFFKTDP 
       210        220        230        240        250
KRGPAFTKGL GHGVDLSHIY GETLDRQHKL RLFKDGKMKY QIINGEVYPP 
       260        270        280        290        300
TVKDTQVEMI YPPHIPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD 
       310        320        330        340        350
VLKQEHPEWD DERLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE 
       360        370        380        390        400
LLFNQQFQYQ NRIAAEFNTL YHWHPLLPDT FQIDDQEYNF QQFLYNNSIL 
       410        420        430        440        450
LEHGLTQFVE SFSRQIAGRV AGGRNVPAAA QKIAKASIDQ SREMKYQSLN 
       460        470        480        490        500
EYRKRFRLTP YKSFEELTGE KEMAAELEAL YGDIDAMELY PALLVEKPRP 
       510        520        530        540        550
DAIFGETMVE LGAPFSLKGL LGNPICSPDY WKPSTFGGEV GFKIINTASI 
       560        570        580        590        600
QSLICNNVKG CPFTAFSVQD PQLSKAVTIN ASASHSGLDD VNPTVLLKER 

STEL

Length:604

Mass (Da):68,847

Last modified:January 1, 1998 - v1

Checksum:ⁱ2B792F7FEB513068

GO

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF027335 Genomic DNA Translation: AAC48808.1 AF027334 mRNA Translation: AAC07911.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001075244.1, NM_001081775.2
UniGeneⁱ	Eca.3397

Genome annotation databases

Ensemblⁱ	ENSECAT00000018514; ENSECAP00000015107; ENSECAG00000017181
GeneIDⁱ	791253
KEGGⁱ	ecb:791253

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length
O19183	Prostaglandin G/H synthase-2 (Fragment)		HORSE		79
prostaglandin G/H synthase 2		ERIEU		681
Prostaglandin G/H synthase 2 precursor		PIG		604
UPI0002C65C9B		southern white rhinoceros		604
UPI0003C8865B		CAMFR		604
+7

Protein	Similar proteins		Species	Score	Length
O19183	Prostaglandin G/H synthase 1		HUMAN		599
Prostaglandin G/H synthase 1		HETGA		666
UPI000333BFCA		OCTDE		602
UPI000980E5C3		CASCN		601
UPI0005402885		FUKDA		600
+549

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF027335 Genomic DNA Translation: AAC48808.1 AF027334 mRNA Translation: AAC07911.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001075244.1, NM_001081775.2
UniGeneⁱ	Eca.3397

3D structure databases

ProteinModelPortalⁱ	O19183
SMRⁱ	O19183
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

STRINGⁱ	9796.ENSECAP00000015107

STRINGⁱ

9796.ENSECAP00000015107

Protein family/group databases

PeroxiBaseⁱ	4123 EcabPGHS02

PeroxiBaseⁱ

4123 EcabPGHS02

Proteomic databases

PaxDbⁱ	O19183

PaxDbⁱ

O19183

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSECAT00000018514; ENSECAP00000015107; ENSECAG00000017181
GeneIDⁱ	791253
KEGGⁱ	ecb:791253

Organism-specific databases

CTDⁱ	5743
VGNCⁱ	VGNC:21997 PTGS2

Phylogenomic databases

eggNOGⁱ	KOG2408 Eukaryota ENOG410XPZ3 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000010743
HOGENOMⁱ	HOG000013149
HOVERGENⁱ	HBG000366
InParanoidⁱ	O19183
KEGG Orthology (KO) More...KOⁱ	K11987
OMAⁱ	CNNVKGC
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G03CD
TreeFamⁱ	TF329675

Enzyme and pathway databases

UniPathwayⁱ	UPA00662

UniPathwayⁱ

UPA00662

Gene expression databases

Bgeeⁱ	ENSECAG00000017181

Bgeeⁱ

ENSECAG00000017181

Family and domain databases

Gene3Dⁱ	1.10.640.10, 1 hit
InterProⁱ	View protein in InterPro IPR029576 COX-2 IPR000742 EGF-like_dom IPR010255 Haem_peroxidase IPR019791 Haem_peroxidase_animal IPR037120 Haem_peroxidase_sf
PANTHERⁱ	PTHR11903:SF8 PTHR11903:SF8, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF03098 An_peroxidase, 2 hits PF00008 EGF, 1 hit
PRINTSⁱ	PR00457 ANPEROXIDASE
SUPFAMⁱ	SSF48113 SSF48113, 1 hit
PROSITEⁱ	View protein in PROSITE PS50026 EGF_3, 1 hit PS50292 PEROXIDASE_3, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	PGH2_HORSE
Accessionⁱ	O19183Primary (citable) accession number: O19183
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
	Last sequence update:	January 1, 1998
	Last modified:	May 23, 2018
	This is version 137 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - O19183 (PGH2_HORSE)

Your basket is currently empty. i <p>When browsing through different UniProt proteins, you can use the ‘basket’ to save them, so that you can back to find or analyse them later.<p><a href='/help/basket' target='_top'>More...</a></p>

Prostaglandin G/H synthase 2

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: prostaglandin biosynthesis

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Endoplasmic reticulum

Endoplasmic reticulum

Other locations

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

UniProt is an ELIXIR core data resource

Your basket is currently empty. ⁱ

Functionⁱ

Pathwayⁱ: prostaglandin biosynthesis

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ