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Protein

Prostaglandin G/H synthase 1

Gene

Ptgs1

Organism
Mus musculus (Mouse)
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

Pathwayi

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

  1. dioxygenase activity Source: UniProtKB-KW
  2. heme binding Source: InterPro
  3. metal ion binding Source: UniProtKB-KW
  4. peroxidase activity Source: UniProtKB-KW
  5. prostaglandin-endoperoxide synthase activity Source: MGI

GO - Biological processi

  1. cyclooxygenase pathway Source: MGI
  2. inflammatory response Source: InterPro
  3. keratinocyte differentiation Source: UniProtKB
  4. prostaglandin biosynthetic process Source: MGI
  5. prostaglandin metabolic process Source: MGI
  6. regulation of blood pressure Source: MGI
  7. regulation of cell proliferation Source: MGI
  8. 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_338496. COX reactions.
REACT_349058. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei3361. MmPGHS01.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:97797. Ptgs1.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  3. extracellular vesicular exosome Source: MGI
  4. photoreceptor outer segment Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626Add
BLAST
Chaini27 – 602576Prostaglandin G/H synthase 1PRO_0000023869Add
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
Disulfide bondi571 ↔ 577By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP22437.
PaxDbiP22437.
PRIDEiP22437.

PTM databases

PhosphoSiteiP22437.

Expressioni

Gene expression databases

BgeeiP22437.
CleanExiMM_PTGS1.
ExpressionAtlasiP22437. baseline and differential.
GenevestigatoriP22437.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

BioGridi202462. 2 interactions.
IntActiP22437. 3 interactions.
MINTiMINT-4107353.

Structurei

3D structure databases

ProteinModelPortaliP22437.
SMRiP22437. 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.
InParanoidiP22437.
KOiK00509.
OMAiFKTSGKM.
OrthoDBiEOG7RFTHC.
PhylomeDBiP22437.
TreeFamiTF329675.

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.

P22437-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRRSLSLWF PLLLLLLLPP TPSVLLADPG VPSPVNPCCY YPCQNQGVCV
60 70 80 90 100
RFGLDNYQCD CTRTGYSGPN CTIPEIWTWL RNSLRPSPSF THFLLTHGYW
110 120 130 140 150
LWEFVNATFI REVLMRLVLT VRSNLIPSPP TYNSAHDYIS WESFSNVSYY
160 170 180 190 200
TRILPSVPKD CPTPMGTKGK KQLPDVQLLA QQLLLRREFI PAPQGTNILF
210 220 230 240 250
AFFAQHFTHQ FFKTSGKMGP GFTKALGHGV DLGHIYGDNL ERQYHLRLFK
260 270 280 290 300
DGKLKYQVLD GEVYPPSVEQ ASVLMRYPPG VPPERQMAVG QEVFGLLPGL
310 320 330 340 350
MLFSTIWLRE HNRVCDLLKE EHPTWDDEQL FQTTRLILIG ETIKIVIEEY
360 370 380 390 400
VQHLSGYFLQ LKFDPELLFR AQFQYRNRIA MEFNHLYHWH PLMPNSFQVG
410 420 430 440 450
SQEYSYEQFL FNTSMLVDYG VEALVDAFSR QRAGRIGGGR NFDYHVLHVA
460 470 480 490 500
VDVIKESREM RLQPFNEYRK RFGLKPYTSF QELTGEKEMA AELEELYGDI
510 520 530 540 550
DALEFYPGLL LEKCQPNSIF GESMIEMGAP FSLKGLLGNP ICSPEYWKPS
560 570 580 590 600
TFGGDVGFNL VNTASLKKLV CLNTKTCPYV SFRVPDYPGD DGSVLVRRST

EL
Length:602
Mass (Da):69,042
Last modified:August 1, 1991 - v1
Checksum:i634C0E602045C3A0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34141 mRNA. Translation: AAA39913.1.
BC005573 mRNA. Translation: AAH05573.1.
CCDSiCCDS15970.1.
PIRiA35564.
RefSeqiNP_032995.1. NM_008969.4.
XP_006497853.1. XM_006497790.2.
XP_006497854.1. XM_006497791.2.
XP_006497856.1. XM_006497793.2.
UniGeneiMm.275434.

Genome annotation databases

EnsembliENSMUST00000062069; ENSMUSP00000059977; ENSMUSG00000047250.
GeneIDi19224.
KEGGimmu:19224.
UCSCiuc008jll.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34141 mRNA. Translation: AAA39913.1.
BC005573 mRNA. Translation: AAH05573.1.
CCDSiCCDS15970.1.
PIRiA35564.
RefSeqiNP_032995.1. NM_008969.4.
XP_006497853.1. XM_006497790.2.
XP_006497854.1. XM_006497791.2.
XP_006497856.1. XM_006497793.2.
UniGeneiMm.275434.

3D structure databases

ProteinModelPortaliP22437.
SMRiP22437. Positions 34-586.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202462. 2 interactions.
IntActiP22437. 3 interactions.
MINTiMINT-4107353.

Chemistry

BindingDBiP22437.
ChEMBLiCHEMBL2649.

Protein family/group databases

PeroxiBasei3361. MmPGHS01.

PTM databases

PhosphoSiteiP22437.

Proteomic databases

MaxQBiP22437.
PaxDbiP22437.
PRIDEiP22437.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000062069; ENSMUSP00000059977; ENSMUSG00000047250.
GeneIDi19224.
KEGGimmu:19224.
UCSCiuc008jll.1. mouse.

Organism-specific databases

CTDi5742.
MGIiMGI:97797. Ptgs1.

Phylogenomic databases

eggNOGiNOG39991.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiP22437.
KOiK00509.
OMAiFKTSGKM.
OrthoDBiEOG7RFTHC.
PhylomeDBiP22437.
TreeFamiTF329675.

Enzyme and pathway databases

UniPathwayiUPA00662.
ReactomeiREACT_338496. COX reactions.
REACT_349058. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).

Miscellaneous databases

ChiTaRSiPtgs1. mouse.
NextBioi296008.
PROiP22437.
SOURCEiSearch...

Gene expression databases

BgeeiP22437.
CleanExiMM_PTGS1.
ExpressionAtlasiP22437. baseline and differential.
GenevestigatoriP22437.

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

« Hide 'large scale' publications
  1. "The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases."
    Dewitt D.L., El-Harith E.A., Kraemer S.A., Andrews M.J., Yao E.F., Armstrong R.L., Smith W.L.
    J. Biol. Chem. 265:5192-5198(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary gland.
  3. "Cyclooxygenases: structural, cellular, and molecular biology."
    Smith W.L., DeWitt D.L., Garavito R.M.
    Annu. Rev. Biochem. 69:145-182(1999) [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(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL CANCER.

Entry informationi

Entry nameiPGH1_MOUSE
AccessioniPrimary (citable) accession number: P22437
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: April 1, 2015
This is version 156 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.