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O97554 (PGH1_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 89. 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:COX1
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

Protein attributes

Sequence length606 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 By similarity. Endoplasmic reticulum membrane; Peripheral membrane protein 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.

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 – 3030 Potential
Chain31 – 606576Prostaglandin G/H synthase 1
PRO_0000041818

Regions

Domain38 – 7639EGF-like

Sites

Active site2131Proton acceptor By similarity
Active site3911For cyclooxygenase activity By similarity
Metal binding3941Iron (heme axial ligand) By similarity
Site5361Aspirin-acetylated serine By similarity

Amino acid modifications

Glycosylation741N-linked (GlcNAc...) Potential
Glycosylation1101N-linked (GlcNAc...) Potential
Glycosylation1501N-linked (GlcNAc...) Potential
Glycosylation4161N-linked (GlcNAc...) Potential
Disulfide bond42 ↔ 53 By similarity
Disulfide bond43 ↔ 165 By similarity
Disulfide bond47 ↔ 63 By similarity
Disulfide bond65 ↔ 75 By similarity
Disulfide bond575 ↔ 581 By similarity

Sequences

Sequence LengthMass (Da)Tools
O97554 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: DB751FD1E2F1CD77

FASTA60669,076
        10         20         30         40         50         60 
MSRSSPSLRL PVLLLLLLLL LLPPPPPVLP ADPGAPAPVN PCCYFPCQHQ GVCVRVALDR 

        70         80         90        100        110        120 
YQCDCTRTGY SGPNCTVPDL WTWLRSSLRP SPTFVHYLLT HVRWFWEFVN ATFIRDTLMR 

       130        140        150        160        170        180 
LVLTVRSNLI PSPPTYNLDY DYISWEAFSN VSYYTRVLPS VPKDCPTPMG TKGKKQLPDA 

       190        200        210        220        230        240 
QVLAHRFLLR RTFIPDPQGT NLMFAFFAQH FTHQFFKTSG KMGPGFTKAL GHGVDLGHIY 

       250        260        270        280        290        300 
GDSLERQYHL RLFKDGKLKY QVLDGEVYPP SVEEAPVLMH YPRGVPPRSQ MAVGQEVFGL 

       310        320        330        340        350        360 
LPGLMLYATL WLREHNRVCD LLKAEHPTWD DEQLFQTTRL ILIGETIKIV IEEYVQQLSG 

       370        380        390        400        410        420 
YFLQLKFDPE MLFSVQFQYR NRIAMEFNHL YHWHPLMPDS FQVGSQEYSY EQFLFNTSML 

       430        440        450        460        470        480 
VDYGVEALVD AFSRQSAGRI GGGRNIDHHV LHVAVEVIKE SREMRLQPFN EYRKRFGLKP 

       490        500        510        520        530        540 
YASFQELTGE TEMAAELEEL YGDIDALEFY PGLLLEKCQP NSIFGESMIE IGAPFSLKGL 

       550        560        570        580        590        600 
LGNPICSPEY WKPSTFGGEV GSNLIKTATL KKLVCLNTKT CPYVSFRVPR SSGDDGPAAE 


RRSTEL 

« Hide

References

[1]"Intrarenal localization of cyclooxygenase-1 and -2 and their differential expression in acute hydronephrotic kidney."
Guan Y., Zhang Y., Breyer R.M., Davis L., Redha R., Chang S., Breyer M.D.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: New Zealand white.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF026008 mRNA. Translation: AAD01796.1.
RefSeqNP_001076150.1. NM_001082681.1.
UniGeneOcu.2320.

3D structure databases

ProteinModelPortalO97554.
SMRO97554. Positions 37-589.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9986.ENSOCUP00000016903.

Chemistry

BindingDBO97554.
ChEMBLCHEMBL3334.

Protein family/group databases

PeroxiBase4131. OcuPGHS01.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100009407.

Organism-specific databases

CTD100136038.

Phylogenomic databases

eggNOGNOG39991.
HOGENOMHOG000013149.
HOVERGENHBG000366.

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. 2 hits.
[Graphical view]
PRINTSPR00457. ANPEROXIDASE.
SMARTSM00181. EGF. 1 hit.
[Graphical view]
SUPFAMSSF48113. SSF48113. 1 hit.
PROSITEPS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry namePGH1_RABIT
AccessionPrimary (citable) accession number: O97554
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: May 1, 1999
Last modified: May 14, 2014
This is version 89 of the entry and version 1 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