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O62664 (PGH1_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended 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 names
Name:PTGS1
Synonyms:COX-1, COX1
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length600 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.

Cofactor

Binds 1 heme B (iron-protoporphyrin IX) group per subunit By similarity.

Pathway

Lipid metabolism; prostaglandin biosynthesis.

Subunit structure

Homodimer By similarity.

Subcellular location

Microsome membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein.

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.

Sequence similarities

Belongs to the prostaglandin G/H synthase family.

Contains 1 EGF-like domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 600576Prostaglandin G/H synthase 1
PRO_0000163113

Regions

Domain32 – 7039EGF-like

Sites

Active site2071Proton acceptor By similarity
Active site3851For cyclooxygenase activity By similarity
Metal binding3881Iron (heme axial ligand) By similarity
Site5301Aspirin-acetylated serine By similarity

Amino acid modifications

Glycosylation681N-linked (GlcNAc...) Potential
Glycosylation1041N-linked (GlcNAc...) Potential
Glycosylation1441N-linked (GlcNAc...) Potential
Glycosylation4101N-linked (GlcNAc...) Potential
Disulfide bond36 ↔ 47 By similarity
Disulfide bond37 ↔ 159 By similarity
Disulfide bond41 ↔ 57 By similarity
Disulfide bond59 ↔ 69 By similarity
Disulfide bond569 ↔ 575 By similarity

Experimental info

Sequence conflict2291D → G in AAC05591. Ref.2
Sequence conflict2411Q → R in AAC05591. Ref.2
Sequence conflict2631P → Q in AAC05591. Ref.2
Sequence conflict3201H → Q in AAC05591. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O62664 [UniParc].

Last modified February 5, 2008. Version 2.
Checksum: 0B43E65DA9E2A2E9

FASTA60068,805
        10         20         30         40         50         60 
MSRQGISLRF PLLLLLLSPS PVLPADPGAP APVNPCCYYP CQHQGICVRF GLDRYQCDCT 

        70         80         90        100        110        120 
RTGYYGPNCT IPEIWTWLRT TLRPSPSFVH FLLTHGRWLW DFVNATFIRD KLMRLVLTVR 

       130        140        150        160        170        180 
SNLIPSPPTY NVAHDYISWE SFSNVSYYTR ILPSVPRDCP TPMGTKGKKQ LPDAEFLSRR 

       190        200        210        220        230        240 
FLLRRKFIPD PQGTNLMFAF FAQHFTHQFF KTSGKMGPGF TKALGHGVDL GHIYGDNLER 

       250        260        270        280        290        300 
QYQLRLFKDG KLKYQMLNGE VYPPSVEEAP VLMHYPRGIP PQSQMAVGQE VFGLLPGLMV 

       310        320        330        340        350        360 
YATIWLREHN RVCDLLKAEH PTWGDEQLFQ TARLILIGET IKIVIEEYVQ QLSGYFLQLK 

       370        380        390        400        410        420 
FDPELLFGAQ FQYRNRIAME FNQLYHWHPL MPDSFRVGPQ DYSYEQFLFN TSMLVDYGVE 

       430        440        450        460        470        480 
ALVDAFSRQP AGRIGGGRNI DHHILHVAVD VIKESRELRL QPFNEYRKRF GMKPYTSFQE 

       490        500        510        520        530        540 
LTGEKEMAAE LEELYGDIDA LEFYPGLLLE KCHPNSIFGE SMIEMGAPFS LKGLLGNPIC 

       550        560        570        580        590        600 
SPEYWKASTF GGDVGFNLVK TATLKKLVCL NTKTCPYVSF HVPDPHREDR PGVERPPTEL 

« Hide

References

« Hide 'large scale' references
[1]NIH - Mammalian Gene Collection (MGC) project
Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Hereford.
Tissue: Ascending colon.
[2]"Cellular mechanisms involved during oxytocin-induced prostaglandin F2alpha production in endometrial epithelial cells in vitro: role of cyclooxygenase-2."
Asselin E., Drolet P., Fortier M.A.
Endocrinology 138:4798-4805(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 121-379.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC134517 mRNA. Translation: AAI34518.1.
AF004943 mRNA. Translation: AAC05591.1.
RefSeqNP_001098793.1. NM_001105323.1.
UniGeneBt.2151.

3D structure databases

ProteinModelPortalO62664.
SMRO62664. Positions 32-584.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBO62664.
ChEMBLCHEMBL2860.

Protein family/group databases

PeroxiBase3332. BtPGHS01.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000008833; ENSBTAP00000008833; ENSBTAG00000006716.
GeneID282022.
KEGGbta:282022.

Organism-specific databases

CTD5742.

Phylogenomic databases

eggNOGNOG39991.
GeneTreeENSGT00390000010743.
HOGENOMHOG000013149.
HOVERGENHBG000366.
InParanoidO62664.
KOK00509.
OMAFKTSGKM.
OrthoDBEOG7RFTHC.
TreeFamTF329675.

Enzyme and pathway databases

UniPathwayUPA00662.

Family and domain databases

Gene3D1.10.640.10. 1 hit.
InterProIPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR002007. Haem_peroxidase_animal.
IPR019791. Haem_peroxidase_animal_subgr.
[Graphical view]
PfamPF03098. An_peroxidase. 1 hit.
[Graphical view]
PRINTSPR00457. ANPEROXIDASE.
SUPFAMSSF48113. SSF48113. 1 hit.
PROSITEPS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio20805886.

Entry information

Entry namePGH1_BOVIN
AccessionPrimary (citable) accession number: O62664
Secondary accession number(s): A7YWD4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: February 5, 2008
Last modified: June 11, 2014
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways