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O19183

- PGH2_HORSE

UniProt

O19183 - PGH2_HORSE

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Protein
Prostaglandin G/H synthase 2
Gene
PTGS2, COX2
Organism
Equus caballus (Horse)
Status
Reviewed - 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.

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 sitei106 – 1061Substrate By similarity
Active sitei193 – 1931Proton acceptor By similarity
Binding sitei341 – 3411Substrate By similarity
Active sitei371 – 3711For cyclooxygenase activity By similarity
Binding sitei371 – 3711Substrate By similarity
Metal bindingi374 – 3741Iron (heme axial ligand) By similarity
Sitei516 – 5161Aspirin-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. anagen Source: Ensembl
  2. brown fat cell differentiation Source: Ensembl
  3. cellular response to hypoxia Source: Ensembl
  4. cyclooxygenase pathway Source: UniProtKB
  5. positive regulation of brown fat cell differentiation Source: Ensembl
  6. positive regulation of fever generation Source: Ensembl
  7. prostaglandin biosynthetic process Source: UniProtKB
  8. regulation of blood pressure Source: UniProtKB
  9. regulation of cell proliferation Source: Ensembl
  10. 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

UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei4123. 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
OrganismiEquus caballus (Horse)
Taxonomic identifieri9796 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaPerissodactylaEquidaeEquus
ProteomesiUP000002281: Chromosome 5

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
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717 By similarity
Add
BLAST
Chaini18 – 604587Prostaglandin G/H synthase 2
PRO_0000023874Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi21 ↔ 32 By similarity
Disulfide bondi22 ↔ 145 By similarity
Disulfide bondi26 ↔ 42 By similarity
Disulfide bondi44 ↔ 54 By similarity
Glycosylationi53 – 531N-linked (GlcNAc...) Reviewed prediction
Glycosylationi130 – 1301N-linked (GlcNAc...) Reviewed prediction
Glycosylationi396 – 3961N-linked (GlcNAc...) Reviewed prediction
Modified residuei526 – 5261S-nitrosocysteine By similarity
Disulfide bondi555 ↔ 561 By similarity
Glycosylationi580 – 5801N-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-526 By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, S-nitrosylation

Interactioni

Subunit structurei

Homodimer By similarity.

Structurei

3D structure databases

ProteinModelPortaliO19183.
SMRiO19183. Positions 18-569.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 5538EGF-like
Add
BLAST

Sequence similaritiesi

Contains 1 EGF-like domain.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG39991.
GeneTreeiENSGT00390000010743.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiO19183.
KOiK11987.
OMAiICNNVKG.
OrthoDBiEOG7RFTHC.
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.

O19183-1 [UniParc]FASTAAdd to Basket

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MLARALLLCV ALALGHAANP CCSNPCQNRG VCMSVGFDQY QCDCTRTGFY    50
GENCSTPEFL TRIKLFLKPT PNTVHYILTH FKGVWNIVNS FPFLRNAVMK 100
YVLVSRSHLI ESPPTYNAQY GYKSWESFSN LSYYTRALPP VADGCPTPMG 150
VKGKKELPDS KEIVEKFLLR RKFIPDPQGT NMMFAFFAQH FTHQFFKTDP 200
KRGPAFTKGL GHGVDLSHIY GETLDRQHKL RLFKDGKMKY QIINGEVYPP 250
TVKDTQVEMI YPPHIPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD 300
VLKQEHPEWD DERLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE 350
LLFNQQFQYQ NRIAAEFNTL YHWHPLLPDT FQIDDQEYNF QQFLYNNSIL 400
LEHGLTQFVE SFSRQIAGRV AGGRNVPAAA QKIAKASIDQ SREMKYQSLN 450
EYRKRFRLTP YKSFEELTGE KEMAAELEAL YGDIDAMELY PALLVEKPRP 500
DAIFGETMVE LGAPFSLKGL LGNPICSPDY WKPSTFGGEV GFKIINTASI 550
QSLICNNVKG CPFTAFSVQD PQLSKAVTIN ASASHSGLDD VNPTVLLKER 600
STEL 604
Length:604
Mass (Da):68,847
Last modified:January 1, 1998 - v1
Checksum:i2B792F7FEB513068
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF027335 Genomic DNA. Translation: AAC48808.1.
AF027334 mRNA. Translation: AAC07911.1.
RefSeqiNP_001075244.1. NM_001081775.1.
UniGeneiEca.3397.

Genome annotation databases

EnsembliENSECAT00000018514; ENSECAP00000015107; ENSECAG00000017181.
GeneIDi791253.
KEGGiecb:791253.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF027335 Genomic DNA. Translation: AAC48808.1 .
AF027334 mRNA. Translation: AAC07911.1 .
RefSeqi NP_001075244.1. NM_001081775.1.
UniGenei Eca.3397.

3D structure databases

ProteinModelPortali O19183.
SMRi O19183. Positions 18-569.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

PeroxiBasei 4123. EcabPGHS02.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

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

Organism-specific databases

CTDi 5743.

Phylogenomic databases

eggNOGi NOG39991.
GeneTreei ENSGT00390000010743.
HOGENOMi HOG000013149.
HOVERGENi HBG000366.
InParanoidi O19183.
KOi K11987.
OMAi ICNNVKG.
OrthoDBi EOG7RFTHC.
TreeFami TF329675.

Enzyme and pathway databases

UniPathwayi UPA00662 .

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 characterization of equine prostaglandin G/H synthase-2 and regulation of its messenger ribonucleic acid in preovulatory follicles."
    Boerboom D., Sirois J.
    Endocrinology 139:1662-1670(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].

Entry informationi

Entry nameiPGH2_HORSE
AccessioniPrimary (citable) accession number: O19183
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 1, 1998
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, 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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