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Protein

Prostaglandin G/H synthase 2

Gene

PTGS2

Organism
Neovison vison (American mink) (Mustela vison)
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

Pathwayi: 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)DescriptionActionsGraphical viewLength
Binding sitei106SubstrateBy similarity1
Active sitei193Proton acceptorPROSITE-ProRule annotation1
Binding sitei341SubstrateBy similarity1
Active sitei371For cyclooxygenase activityBy similarity1
Binding sitei371SubstrateBy similarity1
Metal bindingi374Iron (heme axial ligand)PROSITE-ProRule annotation1
Sitei516Aspirin-acetylated serineBy similarity1

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

UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei4136. MvPGHS02.

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
OrganismiNeovison vison (American mink) (Mustela vison)
Taxonomic identifieri452646 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaMustelidaeMustelinaeNeovison

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17By similarityAdd BLAST17
ChainiPRO_000002387718 – 604Prostaglandin G/H synthase 2Add BLAST587

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi21 ↔ 32By similarity
Disulfide bondi22 ↔ 145By similarity
Disulfide bondi26 ↔ 42By similarity
Disulfide bondi44 ↔ 54By similarity
Glycosylationi53N-linked (GlcNAc...)Sequence analysis1
Glycosylationi130N-linked (GlcNAc...)Sequence analysis1
Glycosylationi396N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi555 ↔ 561By similarity
Glycosylationi580N-linked (GlcNAc...)Sequence analysis1

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

Interactioni

Subunit structurei

Homodimer.By similarity

Structurei

3D structure databases

ProteinModelPortaliO62725.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 55EGF-likePROSITE-ProRule annotationAdd BLAST38

Sequence similaritiesi

Belongs to the prostaglandin G/H synthase family.Curated
Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

HOVERGENiHBG000366.

Family and domain databases

Gene3Di1.10.640.10. 1 hit.
InterProiIPR029576. COX-2.
IPR000742. EGF-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view]
PANTHERiPTHR11903:SF8. PTHR11903:SF8. 1 hit.
PfamiPF03098. An_peroxidase. 1 hit.
PF00008. EGF. 1 hit.
[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.

O62725-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLARAGLLCA SLSPPHAANP CCSNPCQNQG VCMSIGFDQY MCDCSRTGFY
60 70 80 90 100
GENCSTPEFL TRVKLLLKPT PNTVHYILTH FKGVWNIVNK IPFLADVIMK
110 120 130 140 150
YVRTSRSHCI EPPPTYNVHY AYKSWEAFSN LSYYTRALPP VADDCPTPMG
160 170 180 190 200
VKGKKELPDS KEIVEKFLLR RKFIPDPQGT NMMFAFFAQH FTHQFFKTDH
210 220 230 240 250
KRGPGFTKGL GHGVDLSHVY GETLDRQHKL RLFKDGKMKY QVIDGEVYPP
260 270 280 290 300
TVKDTQVEMI YPPHVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD
310 320 330 340 350
VLKQEQGEWD DERLFRRSRL ILIGETIKIV IEDYVRHLSG YHFSLKFDPE
360 370 380 390 400
LLFNQQFQYQ NRIAAEFNTL YHWHPLLPDT LQIDDQEYNF QQFVYNNSIL
410 420 430 440 450
LEHGLTQFGE SFSRQIAGRV AGGRNVPAAV QQEQRASIDQ SRQMKYQSLN
460 470 480 490 500
EYRKRFSVKP YASFEELTGE KEMAGELKAL YQDIDAMELY PALLVEKPRP
510 520 530 540 550
DAIFGETMVE IGAPFSLKGL MGNPICSPDY WKPSHFGGEV GFKIINTASI
560 570 580 590 600
QSLICNNVKG CPFTAFSVQD PQLTKTVTIN GSSSHSGLDD INPTVLLKER

STEL
Length:604
Mass (Da):68,950
Last modified:August 1, 1998 - v1
Checksum:iE28D19F47CD926F8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF047841 mRNA. Translation: AAC05637.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF047841 mRNA. Translation: AAC05637.1.

3D structure databases

ProteinModelPortaliO62725.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

PeroxiBasei4136. MvPGHS02.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG000366.

Enzyme and pathway databases

UniPathwayiUPA00662.

Family and domain databases

Gene3Di1.10.640.10. 1 hit.
InterProiIPR029576. COX-2.
IPR000742. EGF-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view]
PANTHERiPTHR11903:SF8. PTHR11903:SF8. 1 hit.
PfamiPF03098. An_peroxidase. 1 hit.
PF00008. EGF. 1 hit.
[Graphical view]
PRINTSiPR00457. ANPEROXIDASE.
SUPFAMiSSF48113. SSF48113. 1 hit.
PROSITEiPS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPGH2_NEOVI
AccessioniPrimary (citable) accession number: O62725
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: August 1, 1998
Last modified: October 5, 2016
This is version 110 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.

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.