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O02768

- PGH2_RABIT

UniProt

O02768 - PGH2_RABIT

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Protein

Prostaglandin G/H synthase 2

Gene

PTGS2

Organism
Oryctolagus cuniculus (Rabbit)
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. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells (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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei106 – 1061SubstrateBy similarity
Active sitei193 – 1931Proton acceptorPROSITE-ProRule annotation
Binding sitei341 – 3411SubstrateBy similarity
Active sitei371 – 3711For cyclooxygenase activityBy similarity
Binding sitei371 – 3711SubstrateBy similarity
Metal bindingi374 – 3741Iron (heme axial ligand)PROSITE-ProRule annotation
Sitei516 – 5161Aspirin-acetylated serineBy 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. inflammatory response Source: InterPro
  6. positive regulation of brown fat cell differentiation Source: Ensembl
  7. positive regulation of fever generation Source: Ensembl
  8. prostaglandin biosynthetic process Source: UniProtKB
  9. regulation of blood pressure Source: UniProtKB
  10. regulation of cell proliferation Source: Ensembl
  11. 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

PeroxiBasei4130. OcuPGHS02.

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:COX-2, COX2
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
ProteomesiUP000001811: Chromosome 16

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. endoplasmic reticulum Source: UniProtKB-KW
  3. membrane Source: UniProtKB-KW
  4. neuron projection Source: Ensembl
  5. 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 – 1717By similarityAdd
BLAST
Chaini18 – 604587Prostaglandin G/H synthase 2PRO_0000023878Add
BLAST

Amino acid modifications

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

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

Expressioni

Tissue specificityi

Highest expression in kidney and urinary bladder.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000014415.

Structurei

3D structure databases

ProteinModelPortaliO02768.
SMRiO02768. Positions 18-568.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 5538EGF-likePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG39991.
GeneTreeiENSGT00390000010743.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiO02768.
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. 2 hits.
[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.

O02768-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MLARALLLCA AVALSHAANP CCSNPCQNRG VCMTMGFDQY KCDCTRTGFY
60 70 80 90 100
GENCSTPEFL TRIKLLLKPT PDTVHYILTH FKGVWNIVNS IPFLRNSIMK
110 120 130 140 150
YVLTSRSHMI DSPPTYNVHY NYKSWEAFSN LSYYTRALPP VADDCPTPMG
160 170 180 190 200
VKGKKELPDS KDVVEKLLLR RKFIPDPQGT NMMFAFFAQH FTHQFFKTDL
210 220 230 240 250
KRGPAFTKGL GHGVDLNHIY GETLDRQHKL RLFKDGKMKY QVIDGEVYPP
260 270 280 290 300
TVKDTQVEMI YPPHIPAHLQ FAVGQEVFGL VPGLMMYATI WLREHNRVCD
310 320 330 340 350
VLKQEHPEWD DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE
360 370 380 390 400
LLFNQQFQYQ NRIAAEFNTL YHWHPLLPDT FQIDDQQYNY QQFLYNNSIL
410 420 430 440 450
LEHGLTQFVE SFTRQIAGRV AGGRNVPPAV QKVAKASIDQ SRQMKYQSLN
460 470 480 490 500
EYRKRFLLKP YESFEELTGE KEMAAELEAL YGDIDAVELY PALLVERPRP
510 520 530 540 550
DAIFGESMVE MGAPFSLKGL MGNPICSPNY WKPSTFGGEV GFKIVNTASI
560 570 580 590 600
QSLICNNVKG CPFTSFNVPD PQLTKTVTIN ASASHSRLED INPTVLLKGR

STEL
Length:604
Mass (Da):69,007
Last modified:July 1, 1997 - v1
Checksum:iC52F9F5BC1F493D7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U97696 mRNA. Translation: AAB71222.1.
RefSeqiNP_001075857.1. NM_001082388.1.
UniGeneiOcu.2173.

Genome annotation databases

EnsembliENSOCUT00000016770; ENSOCUP00000014415; ENSOCUG00000016771.
GeneIDi100009248.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U97696 mRNA. Translation: AAB71222.1 .
RefSeqi NP_001075857.1. NM_001082388.1.
UniGenei Ocu.2173.

3D structure databases

ProteinModelPortali O02768.
SMRi O02768. Positions 18-568.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9986.ENSOCUP00000014415.

Chemistry

BindingDBi O02768.
ChEMBLi CHEMBL1293198.

Protein family/group databases

PeroxiBasei 4130. OcuPGHS02.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSOCUT00000016770 ; ENSOCUP00000014415 ; ENSOCUG00000016771 .
GeneIDi 100009248.

Organism-specific databases

CTDi 5743.

Phylogenomic databases

eggNOGi NOG39991.
GeneTreei ENSGT00390000010743.
HOGENOMi HOG000013149.
HOVERGENi HBG000366.
InParanoidi O02768.
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. 2 hits.
[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. "Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells."
    Guan Y., Chang M., Cho W., Zhang Y., Redha R., Davis L., Chang S., Dubois R.N., Hao C.M., Breyer M.
    Am. J. Physiol. 273:F18-F26(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: New Zealand white.

Entry informationi

Entry nameiPGH2_RABIT
AccessioniPrimary (citable) accession number: O02768
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 1, 1997
Last modified: November 26, 2014
This is version 119 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