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Q8HZR1 (PGH1_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

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
OrganismCanis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis

Protein attributes

Sequence length603 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein 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 By similarity; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein Ref.1.

Tissue specificity

Brain cortex. Isoform 2 is expressed in the cerebral cortex and heart.

Post-translational modification

N-glycosylated. N-linked glycosylation is necessary for enzymatic activity. Ref.1

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.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q8HZR1-1)

Also known as: COX-1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8HZR1-2)

Also known as: COX-3;

The sequence of this isoform differs from the canonical sequence as follows:
     3-3: R → REFDPEAPRNPLRLPGEPRMPGPALTSRSAG
Isoform 3 (identifier: Q8HZR1-3)

Also known as: PCOX-1a;

The sequence of this isoform differs from the canonical sequence as follows:
     3-3: R → REFDPEAPRNPLRLPGEPRMPGPALTSRSAG
     122-340: Missing.
Note: No enzymatic activity. Membrane-bound.
Isoform 4 (identifier: Q8HZR1-4)

Also known as: PCOX-1b;

The sequence of this isoform differs from the canonical sequence as follows:
     122-340: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 603576Prostaglandin G/H synthase 1
PRO_0000429170

Regions

Domain35 – 7339EGF-like

Sites

Active site2101Proton acceptor By similarity
Active site3881For cyclooxygenase activity By similarity
Metal binding3911Iron (heme axial ligand) By similarity
Site5331Aspirin-acetylated serine By similarity

Amino acid modifications

Glycosylation711N-linked (GlcNAc...) Potential
Glycosylation1071N-linked (GlcNAc...) Potential
Glycosylation1471N-linked (GlcNAc...) Potential
Disulfide bond39 ↔ 50 By similarity
Disulfide bond40 ↔ 162 By similarity
Disulfide bond44 ↔ 60 By similarity
Disulfide bond62 ↔ 72 By similarity
Disulfide bond572 ↔ 578 By similarity

Natural variations

Alternative sequence31R → REFDPEAPRNPLRLPGEPRM PGPALTSRSAG in isoform 2 and isoform 3.
VSP_054856
Alternative sequence122 – 340219Missing in isoform 3 and isoform 4.
VSP_054857

Experimental info

Sequence conflict5971E → Q in AAN33049. Ref.1
Sequence conflict5971E → Q in AAN38739. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (COX-1) [UniParc].

Last modified May 14, 2014. Version 2.
Checksum: 435B3E3A3D5DCCA6

FASTA60369,305
        10         20         30         40         50         60 
MSRGSRLHRW PLLLLLLLLL PPPPVLPAEA RTPAPVNPCC YYPCQHQGIC VRFGLDRYQC 

        70         80         90        100        110        120 
DCTRTGYSGP NCTIPELWTW LRNSLRPSPS FLHFLLTHGR WFWEFINATF IRDMLMRLVL 

       130        140        150        160        170        180 
TARSNLIPSP PTYNIAHDYI SWESFSNVSY YTRVLPSVPQ DCPTPMGTKG KKQLPDAQLL 

       190        200        210        220        230        240 
GRRFLLRRKF IPDPQGTNLM FAFFAQHFTH QFFKTSGKMG PGFTKALGHG VDLGHIYGDN 

       250        260        270        280        290        300 
LDRQYQLRLF KDGKLKYQVL DGEMYPPSVE EAPVLMHYPR GILPQSQMAV GQEVFGLLPG 

       310        320        330        340        350        360 
LMLYATLWLR EHNRVCDLLK AEHPTWGDEQ LFQTARLILI GETIKIVIEE YVQQLSGYFL 

       370        380        390        400        410        420 
QLKFDPELLF SAQFQYRNRI AMEFNQLYHW HPLMPDSFWV GSQEYSYEQF LFNTSMLTHY 

       430        440        450        460        470        480 
GIEALVDAFS RQSAGRIGGG RNIDHHVLHV AVETIKESRE LRLQPFNEYR KRFGMRPYMS 

       490        500        510        520        530        540 
FQELTGEKEM AAELEELYGD IDALEFYPGL LLEKCHPNSI FGESMIEIGA PFSLKGLLGN 

       550        560        570        580        590        600 
PICSPEYWKP STFGGEMGFN MVKTATLKKL VCLNTKTCPY VSFRVPDPHQ DGGPGVERPS 


TEL 

« Hide

Isoform 2 (COX-3) [UniParc].

Checksum: D338221B976BC6BE
Show »

FASTA63372,504
Isoform 3 (PCOX-1a) [UniParc].

Checksum: 75B160CE739015AE
Show »

FASTA41447,512
Isoform 4 (PCOX-1b) [UniParc].

Checksum: 3545A960000ADF22
Show »

FASTA38444,313

References

« Hide 'large scale' references
[1]"COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression."
Chandrasekharan N.V., Dai H., Roos K.L., Evanson N.K., Tomsik J., Elton T.S., Simmons D.L.
Proc. Natl. Acad. Sci. U.S.A. 99:13926-13931(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), ALTERNATIVE SPLICING, GLYCOSYLATION, SUBCELLULAR LOCATION.
Tissue: Brain cortex.
[2]"Genome sequence, comparative analysis and haplotype structure of the domestic dog."
Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B., Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E., Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F., Smith D.R. expand/collapse author list , deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W., Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S., Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A., Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P., Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A., Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P., Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P., Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B., Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A., Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M., Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S., Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L., Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S., Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C., Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G., Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N., Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A., Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A., Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M., Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L., LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A., Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S., Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T., Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A., Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N., Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S., Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M., Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F., Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T., Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C., Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C., Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D., Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H., Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J., Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J., Zembek L., Zimmer A., Lander E.S.
Nature 438:803-819(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Boxer.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF535138 mRNA. Translation: AAN33049.1.
AF535139 mRNA. Translation: AAN38739.1.
AAEX03006907 Genomic DNA. No translation available.
RefSeqNP_001003023.1. NM_001003023.2.
UniGeneCfa.61.

3D structure databases

ProteinModelPortalQ8HZR1.
ModBaseSearch...
MobiDBSearch...

Chemistry

ChEMBLCHEMBL4133.

Protein family/group databases

PeroxiBase3362. CfaPGHS01.

Proteomic databases

PaxDbQ8HZR0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSCAFT00000032279; ENSCAFP00000030061; ENSCAFG00000020263. [Q8HZR1-3]
ENSCAFT00000032287; ENSCAFP00000030067; ENSCAFG00000020263. [Q8HZR1-1]
GeneID403544.
KEGGcfa:403544.

Organism-specific databases

CTD5742.

Phylogenomic databases

eggNOGNOG39991.
GeneTreeENSGT00390000010743.
HOGENOMHOG000013149.
HOVERGENHBG000366.
InParanoidQ8HZR1.
KOK00509.

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...

Other

NextBio20817054.

Entry information

Entry namePGH1_CANFA
AccessionPrimary (citable) accession number: Q8HZR1
Secondary accession number(s): F1PBX3, Q8HZR0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 14, 2014
Last sequence update: May 14, 2014
Last modified: July 9, 2014
This is version 87 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