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Q63921

- PGH1_RAT

UniProt

Q63921 - PGH1_RAT

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Protein

Prostaglandin G/H synthase 1

Gene

Ptgs1

Organism
Rattus norvegicus (Rat)
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.

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. lipid binding Source: RGD
  4. metal ion binding Source: UniProtKB-KW
  5. peroxidase activity Source: UniProtKB-KW
  6. prostaglandin-endoperoxide synthase activity Source: RGD

GO - Biological processi

  1. aging Source: RGD
  2. cyclooxygenase pathway Source: InterPro
  3. inflammatory response Source: InterPro
  4. learning Source: RGD
  5. maintenance of blood-brain barrier Source: RGD
  6. memory Source: RGD
  7. negative regulation of epinephrine secretion Source: RGD
  8. negative regulation of norepinephrine secretion Source: RGD
  9. positive regulation of smooth muscle contraction Source: RGD
  10. positive regulation of vasoconstriction Source: RGD
  11. prostaglandin biosynthetic process Source: UniProtKB
  12. regulation of blood pressure Source: UniProtKB
  13. response to corticosterone Source: RGD
  14. response to fatty acid Source: RGD
  15. response to organonitrogen compound Source: RGD
  16. response to oxidative stress Source: InterPro
  17. 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

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: Unplaced

Organism-specific databases

RGDi3439. Ptgs1.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. endoplasmic reticulum Source: UniProtKB-KW
  3. intracellular membrane-bounded organelle Source: UniProtKB
  4. membrane Source: UniProtKB-KW
  5. nuclear envelope Source: RGD
  6. 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 – 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

GenevestigatoriQ63921.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

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 .
PIRi S39782.
S69198.
UniGenei Rn.44404.

3D structure databases

ProteinModelPortali Q63921.
SMRi Q63921. Positions 34-586.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000010218.

Chemistry

BindingDBi Q63921.
ChEMBLi CHEMBL2095157.

Protein family/group databases

PeroxiBasei 3974. RnoPGHS01.

Proteomic databases

PaxDbi Q63921.
PRIDEi Q63921.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

UCSCi RGD:3439. rat.

Organism-specific databases

RGDi 3439. Ptgs1.

Phylogenomic databases

eggNOGi NOG39991.
HOGENOMi HOG000013149.
HOVERGENi HBG000366.
InParanoidi Q63921.
PhylomeDBi Q63921.

Enzyme and pathway databases

UniPathwayi UPA00662 .

Miscellaneous databases

NextBioi 604139.
PROi Q63921.

Gene expression databases

Genevestigatori Q63921.

Family and domain databases

Gene3Di 1.10.640.10. 1 hit.
InterProi IPR029580. COX-1.
IPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view ]
PANTHERi PTHR11903:SF6. PTHR11903:SF6. 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 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: November 26, 2014
This is version 136 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