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Protein

Prostaglandin G/H synthase 1

Gene

PTGS1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -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

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.

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
Active sitei207Proton acceptorPROSITE-ProRule annotation1
Active sitei385For cyclooxygenase activityBy similarity1
Metal bindingi388Iron (heme axial ligand)PROSITE-ProRule annotation1
Sitei530Aspirin-acetylated serineBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDioxygenase, Oxidoreductase, Peroxidase
Biological processFatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.99.1 908
ReactomeiR-BTA-140180 COX reactions
R-BTA-2162123 Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
UniPathwayiUPA00662

Protein family/group databases

PeroxiBasei3332 BtPGHS01

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 11

Organism-specific databases

VGNCiVGNC:33511 PTGS1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2860

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000016311325 – 600Prostaglandin G/H synthase 1Add BLAST576

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi36 ↔ 47By similarity
Disulfide bondi37 ↔ 159By similarity
Disulfide bondi41 ↔ 57By similarity
Disulfide bondi59 ↔ 69By similarity
Glycosylationi68N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi104N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi144N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi410N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi569 ↔ 575By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO62664
PRIDEiO62664

Expressioni

Gene expression databases

BgeeiENSBTAG00000006716

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000008833

Chemistry databases

BindingDBiO62664

Structurei

3D structure databases

ProteinModelPortaliO62664
SMRiO62664
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 70EGF-likePROSITE-ProRule annotationAdd BLAST39

Sequence similaritiesi

Belongs to the prostaglandin G/H synthase family.Curated

Keywords - Domaini

EGF-like domain, Signal

Phylogenomic databases

eggNOGiKOG2408 Eukaryota
ENOG410XPZ3 LUCA
GeneTreeiENSGT00390000010743
HOGENOMiHOG000013149
HOVERGENiHBG000366
InParanoidiO62664
KOiK00509
OMAiFKTSGKM
OrthoDBiEOG091G03CD
TreeFamiTF329675

Family and domain databases

Gene3Di1.10.640.10, 1 hit
InterProiView protein in InterPro
IPR029580 COX-1
IPR000742 EGF-like_dom
IPR010255 Haem_peroxidase
IPR019791 Haem_peroxidase_animal
IPR037120 Haem_peroxidase_sf
PANTHERiPTHR11903:SF6 PTHR11903:SF6, 1 hit
PfamiView protein in Pfam
PF03098 An_peroxidase, 1 hit
PRINTSiPR00457 ANPEROXIDASE
SUPFAMiSSF48113 SSF48113, 1 hit
PROSITEiView protein in PROSITE
PS50026 EGF_3, 1 hit
PS50292 PEROXIDASE_3, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O62664-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRQGISLRF PLLLLLLSPS PVLPADPGAP APVNPCCYYP CQHQGICVRF
60 70 80 90 100
GLDRYQCDCT RTGYYGPNCT IPEIWTWLRT TLRPSPSFVH FLLTHGRWLW
110 120 130 140 150
DFVNATFIRD KLMRLVLTVR SNLIPSPPTY NVAHDYISWE SFSNVSYYTR
160 170 180 190 200
ILPSVPRDCP TPMGTKGKKQ LPDAEFLSRR FLLRRKFIPD PQGTNLMFAF
210 220 230 240 250
FAQHFTHQFF KTSGKMGPGF TKALGHGVDL GHIYGDNLER QYQLRLFKDG
260 270 280 290 300
KLKYQMLNGE VYPPSVEEAP VLMHYPRGIP PQSQMAVGQE VFGLLPGLMV
310 320 330 340 350
YATIWLREHN RVCDLLKAEH PTWGDEQLFQ TARLILIGET IKIVIEEYVQ
360 370 380 390 400
QLSGYFLQLK FDPELLFGAQ FQYRNRIAME FNQLYHWHPL MPDSFRVGPQ
410 420 430 440 450
DYSYEQFLFN TSMLVDYGVE ALVDAFSRQP AGRIGGGRNI DHHILHVAVD
460 470 480 490 500
VIKESRELRL QPFNEYRKRF GMKPYTSFQE LTGEKEMAAE LEELYGDIDA
510 520 530 540 550
LEFYPGLLLE KCHPNSIFGE SMIEMGAPFS LKGLLGNPIC SPEYWKASTF
560 570 580 590 600
GGDVGFNLVK TATLKKLVCL NTKTCPYVSF HVPDPHREDR PGVERPPTEL
Length:600
Mass (Da):68,805
Last modified:February 5, 2008 - v2
Checksum:i0B43E65DA9E2A2E9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti229D → G in AAC05591 (PubMed:9348208).Curated1
Sequence conflicti241Q → R in AAC05591 (PubMed:9348208).Curated1
Sequence conflicti263P → Q in AAC05591 (PubMed:9348208).Curated1
Sequence conflicti320H → Q in AAC05591 (PubMed:9348208).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC134517 mRNA Translation: AAI34518.1
AF004943 mRNA Translation: AAC05591.1
RefSeqiNP_001098793.1, NM_001105323.1
UniGeneiBt.2151

Genome annotation databases

EnsembliENSBTAT00000008833; ENSBTAP00000008833; ENSBTAG00000006716
GeneIDi282022
KEGGibta:282022

Similar proteinsi

Entry informationi

Entry nameiPGH1_BOVIN
AccessioniPrimary (citable) accession number: O62664
Secondary accession number(s): A7YWD4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: February 5, 2008
Last modified: April 25, 2018
This is version 142 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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