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P27607

- PGH2_CHICK

UniProt

P27607 - PGH2_CHICK

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Protein

Prostaglandin G/H synthase 2

Gene
PTGS2, CEF-147
Organism
Gallus gallus (Chicken)
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. 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

ReactomeiREACT_194363. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_198071. Synthesis of 15-eicosatetraenoic acid derivatives.
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei4107. GgaPGHS02.

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
Mitogen-inducible PGHS
PHS II
Prostaglandin H2 synthase 2
Short name:
PGH synthase 2
Short name:
PGHS-2
Prostaglandin-endoperoxide synthase 2
Gene namesi
Name:PTGS2
Synonyms:CEF-147
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus
ProteomesiUP000000539: 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 – 1717 Reviewed predictionAdd
BLAST
Chaini18 – 603586Prostaglandin G/H synthase 2PRO_0000023881Add
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
Glycosylationi90 – 901N-linked (GlcNAc...) Reviewed prediction
Glycosylationi130 – 1301N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi555 ↔ 561 By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP27607.

Expressioni

Inductioni

By cytokines and mitogens.

Interactioni

Subunit structurei

Homodimer By similarity.

Protein-protein interaction databases

STRINGi9031.ENSGALP00000008111.

Structurei

3D structure databases

ProteinModelPortaliP27607.
SMRiP27607. Positions 18-568.

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Contains 1 EGF-like domain.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG39991.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiP27607.
KOiK11987.
OMAiICNNVKG.
OrthoDBiEOG7RFTHC.
PhylomeDBiP27607.
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. 2 hits.
[Graphical view]
PRINTSiPR00457. ANPEROXIDASE.
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.

P27607-1 [UniParc]FASTAAdd to Basket

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MLLPCALLAA LLAAGHAANP CCSLPCQNRG VCMTTGFDRY ECDCTRTGYY    50
GENCTTPEFF TWLKLILKPT PNTVHYILTH FKGVWNIINN ISFLRDTIMR 100
YVLTSRSHLI DSPPTYNSDY SYKSWEAYSN LSYYTRSLPP VGHDCPTPMG 150
VKGKKELPDS KLIVEKFLLR RKFIPDPQGT NVMFTFFAQH FTHQFFKTDH 200
KKGPGFTKAY GHGVDLNHIY GETLERQLKL RLRKDGKLKY QMIDGEMYPP 250
TVKDTQAEMI YPPHVPEHLQ FSVGQEVFGL VPGLMMYATI WLREHNRVCD 300
VLKQEHPEWD DEQLFQTTRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE 350
LLFNQRFQYQ NRIAAEFNTL YHWHPLLPDT FQIHNQEYTF QQFLYNNSIM 400
LEHGLSHMVK SFSKQSAGRV AGGKNVPAAV QKVAKASIDQ SRQMRYQSLN 450
EYRKRFMLKP FKSFEELTGE KEMAAELEEL YGDIDAMELY PGLLVEKPRP 500
GAIFGETMVE IGAPFSLKGL MGNTICSPEY WKPSTFGGKV GFEIINTASL 550
QKLICNNVKG CPFTAFHVLN PEPTEATINV STSNTAMEDI NPTLLLKEQS 600
AEL 603
Length:603
Mass (Da):69,112
Last modified:August 1, 1992 - v1
Checksum:iBF6DFB337118B231
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M64990 mRNA. Translation: AAA49050.1.
PIRiA38630.
RefSeqiNP_001161190.1. NM_001167718.1.
NP_001161191.1. NM_001167719.1.
UniGeneiGga.4401.

Genome annotation databases

GeneIDi396451.
KEGGigga:396451.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M64990 mRNA. Translation: AAA49050.1 .
PIRi A38630.
RefSeqi NP_001161190.1. NM_001167718.1.
NP_001161191.1. NM_001167719.1.
UniGenei Gga.4401.

3D structure databases

ProteinModelPortali P27607.
SMRi P27607. Positions 18-568.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9031.ENSGALP00000008111.

Protein family/group databases

PeroxiBasei 4107. GgaPGHS02.

Proteomic databases

PaxDbi P27607.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 396451.
KEGGi gga:396451.

Organism-specific databases

CTDi 5743.

Phylogenomic databases

eggNOGi NOG39991.
HOGENOMi HOG000013149.
HOVERGENi HBG000366.
InParanoidi P27607.
KOi K11987.
OMAi ICNNVKG.
OrthoDBi EOG7RFTHC.
PhylomeDBi P27607.
TreeFami TF329675.

Enzyme and pathway databases

UniPathwayi UPA00662 .
Reactomei REACT_194363. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_198071. Synthesis of 15-eicosatetraenoic acid derivatives.

Miscellaneous databases

NextBioi 20816492.
PROi P27607.

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. 2 hits.
[Graphical view ]
PRINTSi PR00457. ANPEROXIDASE.
SUPFAMi SSF48113. SSF48113. 1 hit.
PROSITEi PS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing."
    Xie W., Chipman J.G., Robertson D.L., Erikson R.L., Simmons D.L.
    Proc. Natl. Acad. Sci. U.S.A. 88:2692-2696(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiPGH2_CHICK
AccessioniPrimary (citable) accession number: P27607
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: September 3, 2014
This is version 125 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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