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Protein

Prostaglandin G/H synthase 1

Gene

Ptgs1

Organism
Rattus norvegicus (Rat)
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. 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.

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

Pathway: 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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei209 – 2091Proton acceptorPROSITE-ProRule annotation
Active sitei387 – 3871For cyclooxygenase activityBy similarity
Metal bindingi390 – 3901Iron (heme axial ligand)PROSITE-ProRule annotation
Sitei532 – 5321Aspirin-acetylated serine

GO - Molecular functioni

  • dioxygenase activity Source: UniProtKB-KW
  • heme binding Source: InterPro
  • lipid binding Source: RGD
  • metal ion binding Source: UniProtKB-KW
  • peroxidase activity Source: UniProtKB-KW
  • prostaglandin-endoperoxide synthase activity Source: RGD

GO - Biological processi

  • aging Source: RGD
  • cyclooxygenase pathway Source: InterPro
  • inflammatory response Source: InterPro
  • learning Source: RGD
  • maintenance of blood-brain barrier Source: RGD
  • memory Source: RGD
  • negative regulation of epinephrine secretion Source: RGD
  • negative regulation of norepinephrine secretion Source: RGD
  • positive regulation of smooth muscle contraction Source: RGD
  • positive regulation of vasoconstriction Source: RGD
  • prostaglandin biosynthetic process Source: UniProtKB
  • regulation of blood pressure Source: UniProtKB
  • response to corticosterone Source: RGD
  • response to fatty acid Source: RGD
  • response to organonitrogen compound Source: RGD
  • response to oxidative stress Source: InterPro
  • sensory perception of pain Source: RGD
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

BRENDAi1.14.99.1. 5301.
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei3974. RnoPGHS01.

Names & Taxonomyi

Protein namesi
Recommended name:
Prostaglandin G/H synthase 1 (EC:1.14.99.1)
Alternative name(s):
Cyclooxygenase-1
Short name:
COX-1
Prostaglandin H2 synthase 1
Short name:
PGH synthase 1
Short name:
PGHS-1
Short name:
PHS 1
Prostaglandin-endoperoxide synthase 1
Gene namesi
Name:Ptgs1
Synonyms:Cox-1, Cox1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3439. Ptgs1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626By similarityAdd
BLAST
Chaini27 – 602576Prostaglandin G/H synthase 1PRO_0000023870Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi38 ↔ 49By similarity
Disulfide bondi39 ↔ 161By similarity
Disulfide bondi43 ↔ 59By similarity
Disulfide bondi61 ↔ 71By similarity
Glycosylationi70 – 701N-linked (GlcNAc...)Sequence Analysis
Glycosylationi106 – 1061N-linked (GlcNAc...)Sequence Analysis
Glycosylationi146 – 1461N-linked (GlcNAc...)Sequence Analysis
Glycosylationi412 – 4121N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi571 ↔ 577By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ63921.
PRIDEiQ63921.

Expressioni

Gene expression databases

GenevisibleiQ63921. RN.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

IntActiQ63921. 1 interaction.
STRINGi10116.ENSRNOP00000010218.

Structurei

3D structure databases

ProteinModelPortaliQ63921.
SMRiQ63921. Positions 34-586.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini34 – 7239EGF-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

EGF-like domain, Signal

Phylogenomic databases

eggNOGiNOG39991.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiQ63921.
PhylomeDBiQ63921.

Family and domain databases

Gene3Di1.10.640.10. 1 hit.
InterProiIPR029580. COX-1.
IPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view]
PANTHERiPTHR11903:SF6. PTHR11903:SF6. 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.

Q63921-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRRSLSLQF PLLLLLLLLP PPPVLLTDAG VPSPVNPCCY YPCQNQGVCV
60 70 80 90 100
RFGLDHYQCD CTRTGYSGPN CTIPEIWTWL RSSLRPSPSF THFLLTHGYW
110 120 130 140 150
IWEFVNATFI REVLMRLVIT VRSNLIPSPP TYNTAHDYIS WESFSNVSYY
160 170 180 190 200
TRILPSVPKD CPTPMGTKGK KQLPDIHLLA QRLLLRREFI PGPQGTNVLF
210 220 230 240 250
AFFAQHFTHQ FFKTSGKMGP GFTKALGHGV DLGHIYGDSL ERQYHLRLFK
260 270 280 290 300
DGKLKYQVLD GEVYPPSVEQ ASVLMRYPPG VPPEKQMAVG QEVFGLLPGL
310 320 330 340 350
MLFSTIWLRE HNRVCDLLKE EHPTWDDEQL FQTTRLILIG ETIKIIIEEY
360 370 380 390 400
VQHLSGYFLQ LKFDPELLFR AQFQYRNRIA LEFNHLYHWH PLMPDSFQVG
410 420 430 440 450
SQEYSYEQFL FNTSMLVDYG VEALVDAFSR QRAGRIGGGR NFDYHVLHVA
460 470 480 490 500
EDVIKESREM RLQSFNEYRK RFGLKPYTSF QEFTGEKEMA AELEELYGDI
510 520 530 540 550
DALEFYPGLM LEKCQPNSLF GESMIEMGAP FSLKGLLGNP ICSPEYWKPS
560 570 580 590 600
TFGGDVGFNI VNTASLKKLV CLNTKTCPYV SFRVPDYPGD DGSVFVRPST

EL
Length:602
Mass (Da):69,032
Last modified:December 15, 1998 - v2
Checksum:i0BFAF7EBFDA0C7C2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti36 – 361N → I in AAA03465 (PubMed:8274023).Curated
Sequence conflicti36 – 361N → I in AAB29400 (PubMed:8274023).Curated
Sequence conflicti116 – 1172RL → GW (PubMed:8274023).Curated
Sequence conflicti119 – 1191I → L (PubMed:8274023).Curated
Sequence conflicti192 – 1921G → A in AAA03465 (PubMed:8274023).Curated
Sequence conflicti192 – 1921G → A in AAB29400 (PubMed:8274023).Curated
Sequence conflicti263 – 2631V → L in AAA03465 (PubMed:8274023).Curated
Sequence conflicti263 – 2631V → L in AAB29400 (PubMed:8274023).Curated
Sequence conflicti274 – 2741L → K in AAA03465 (PubMed:8274023).Curated
Sequence conflicti274 – 2741L → K in AAB29400 (PubMed:8274023).Curated
Sequence conflicti290 – 2901G → A in AAA03465 (PubMed:8274023).Curated
Sequence conflicti290 – 2901G → A in AAB29400 (PubMed:8274023).Curated
Sequence conflicti339 – 3391I → R in AAB29400 (PubMed:8274023).Curated
Sequence conflicti344 – 3441K → E in AAA03465 (PubMed:8274023).Curated
Sequence conflicti344 – 3441K → E in AAB29400 (PubMed:8274023).Curated
Sequence conflicti381 – 3811L → M in AAA03465 (PubMed:8274023).Curated
Sequence conflicti381 – 3811L → M in AAB29400 (PubMed:8274023).Curated
Sequence conflicti392 – 3921L → F in AAA03465 (PubMed:8274023).Curated
Sequence conflicti392 – 3921L → F in AAB29400 (PubMed:8274023).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U03388 mRNA. Translation: AAA03465.1.
S67721 mRNA. Translation: AAB29400.2.
U18060 mRNA. Translation: AAA85823.1.
PIRiS39782.
S69198.
UniGeneiRn.44404.

Genome annotation databases

UCSCiRGD:3439. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U03388 mRNA. Translation: AAA03465.1.
S67721 mRNA. Translation: AAB29400.2.
U18060 mRNA. Translation: AAA85823.1.
PIRiS39782.
S69198.
UniGeneiRn.44404.

3D structure databases

ProteinModelPortaliQ63921.
SMRiQ63921. Positions 34-586.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ63921. 1 interaction.
STRINGi10116.ENSRNOP00000010218.

Chemistry

BindingDBiQ63921.
ChEMBLiCHEMBL2095157.

Protein family/group databases

PeroxiBasei3974. RnoPGHS01.

Proteomic databases

PaxDbiQ63921.
PRIDEiQ63921.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:3439. rat.

Organism-specific databases

RGDi3439. Ptgs1.

Phylogenomic databases

eggNOGiNOG39991.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiQ63921.
PhylomeDBiQ63921.

Enzyme and pathway databases

UniPathwayiUPA00662.
BRENDAi1.14.99.1. 5301.

Miscellaneous databases

NextBioi604139.
PROiQ63921.

Gene expression databases

GenevisibleiQ63921. RN.

Family and domain databases

Gene3Di1.10.640.10. 1 hit.
InterProiIPR029580. COX-1.
IPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view]
PANTHERiPTHR11903:SF6. PTHR11903:SF6. 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]
ProtoNetiSearch...

Publicationsi

  1. "Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression."
    Feng L., Sun W., Xia Y., Tang W.W., Chanmugam P., Soyoola E., Wilson C.B., Hwang D.
    Arch. Biochem. Biophys. 307:361-368(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
  2. "Analysis and quantitation of splicing variants of the TPA-inducible PGHS-1 mRNA in rat tracheal epithelial cells."
    Kitzler J., Hill E., Hardman R., Reddy N., Philpot R., Eling T.E.
    Arch. Biochem. Biophys. 316:856-863(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Fischer 344.
    Tissue: Trachea.
  3. "Cyclooxygenases: structural, cellular, and molecular biology."
    Smith W.L., DeWitt D.L., Garavito R.M.
    Annu. Rev. Biochem. 69:145-182(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION; TISSUE SPECIFICITY AND INHIBITION BY NSAIDS.
  4. "Aspirin, cyclooxygenase inhibition and colorectal cancer."
    Sostres C., Gargallo C.J., Lanas A.
    World J. Gastrointest. Pharmacol. Ther. 5:40-49(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL CANCER.

Entry informationi

Entry nameiPGH1_RAT
AccessioniPrimary (citable) accession number: Q63921
Secondary accession number(s): Q62731, Q63684
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: December 15, 1998
Last modified: June 24, 2015
This is version 141 of the entry and version 2 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

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 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.