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Q8HZR1

- PGH1_CANFA

UniProt

Q8HZR1 - PGH1_CANFA

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Protein

Prostaglandin G/H synthase 1

Gene
PTGS1, COX1
Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein 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.

Catalytic activityi

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

Cofactori

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

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei210 – 2101Proton acceptor By similarity
Active sitei388 – 3881For cyclooxygenase activity By similarity
Metal bindingi391 – 3911Iron (heme axial ligand) By similarity
Sitei533 – 5331Aspirin-acetylated serine By similarity

GO - Molecular functioni

  1. dioxygenase activity Source: UniProtKB-KW
  2. heme binding Source: InterPro
  3. metal ion binding Source: UniProtKB-KW
  4. peroxidase activity Source: UniProtKB-KW
  5. prostaglandin-endoperoxide synthase activity Source: UniProtKB-EC

GO - Biological processi

  1. prostaglandin biosynthetic process Source: UniProtKB-UniPathway
  2. response to oxidative stress Source: InterPro
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

ReactomeiREACT_174506. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei3362. CfaPGHS01.

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:COX1
OrganismiCanis familiaris (Dog) (Canis lupus familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
ProteomesiUP000002254: Chromosome 9

Subcellular locationi

Microsome membrane By similarity; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein 1 Publication

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727 Reviewed predictionAdd
BLAST
Chaini28 – 603576Prostaglandin G/H synthase 1PRO_0000429170Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi39 ↔ 50 By similarity
Disulfide bondi40 ↔ 162 By similarity
Disulfide bondi44 ↔ 60 By similarity
Disulfide bondi62 ↔ 72 By similarity
Glycosylationi71 – 711N-linked (GlcNAc...) Reviewed prediction
Glycosylationi107 – 1071N-linked (GlcNAc...) Reviewed prediction
Glycosylationi147 – 1471N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi572 ↔ 578 By similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ8HZR0.

Expressioni

Tissue specificityi

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

Interactioni

Subunit structurei

Homodimer By similarity.

Structurei

3D structure databases

ProteinModelPortaliQ8HZR1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 7339EGF-likeAdd
BLAST

Sequence similaritiesi

Contains 1 EGF-like domain.

Keywords - Domaini

EGF-like domain, Signal

Phylogenomic databases

eggNOGiNOG39991.
GeneTreeiENSGT00390000010743.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiQ8HZR1.
KOiK00509.

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]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. Align

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q8HZR1-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MSRGSRLHRW PLLLLLLLLL PPPPVLPAEA RTPAPVNPCC YYPCQHQGIC    50
VRFGLDRYQC DCTRTGYSGP NCTIPELWTW LRNSLRPSPS FLHFLLTHGR 100
WFWEFINATF IRDMLMRLVL TARSNLIPSP PTYNIAHDYI SWESFSNVSY 150
YTRVLPSVPQ DCPTPMGTKG KKQLPDAQLL GRRFLLRRKF IPDPQGTNLM 200
FAFFAQHFTH QFFKTSGKMG PGFTKALGHG VDLGHIYGDN LDRQYQLRLF 250
KDGKLKYQVL DGEMYPPSVE EAPVLMHYPR GILPQSQMAV GQEVFGLLPG 300
LMLYATLWLR EHNRVCDLLK AEHPTWGDEQ LFQTARLILI GETIKIVIEE 350
YVQQLSGYFL QLKFDPELLF SAQFQYRNRI AMEFNQLYHW HPLMPDSFWV 400
GSQEYSYEQF LFNTSMLTHY GIEALVDAFS RQSAGRIGGG RNIDHHVLHV 450
AVETIKESRE LRLQPFNEYR KRFGMRPYMS FQELTGEKEM AAELEELYGD 500
IDALEFYPGL LLEKCHPNSI FGESMIEIGA PFSLKGLLGN PICSPEYWKP 550
STFGGEMGFN MVKTATLKKL VCLNTKTCPY VSFRVPDPHQ DGGPGVERPS 600
TEL 603
Length:603
Mass (Da):69,305
Last modified:May 14, 2014 - v2
Checksum:i435B3E3A3D5DCCA6
GO
Isoform 2 (identifier: Q8HZR1-2) [UniParc]FASTAAdd to Basket

Also known as: COX-3

The sequence of this isoform differs from the canonical sequence as follows:
     3-3: R → REFDPEAPRNPLRLPGEPRMPGPALTSRSAG

Show »
Length:633
Mass (Da):72,504
Checksum:iD338221B976BC6BE
GO
Isoform 3 (identifier: Q8HZR1-3) [UniParc]FASTAAdd to Basket

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.

Show »
Length:414
Mass (Da):47,512
Checksum:i75B160CE739015AE
GO
Isoform 4 (identifier: Q8HZR1-4) [UniParc]FASTAAdd to Basket

Also known as: PCOX-1b

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

Show »
Length:384
Mass (Da):44,313
Checksum:i3545A960000ADF22
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei3 – 31R → REFDPEAPRNPLRLPGEPRM PGPALTSRSAG in isoform 2 and isoform 3. VSP_054856
Alternative sequencei122 – 340219Missing in isoform 3 and isoform 4. VSP_054857Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti597 – 5971E → Q in AAN33049. 1 Publication
Sequence conflicti597 – 5971E → Q in AAN38739. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF535138 mRNA. Translation: AAN33049.1.
AF535139 mRNA. Translation: AAN38739.1.
AAEX03006907 Genomic DNA. No translation available.
RefSeqiNP_001003023.1. NM_001003023.2.
UniGeneiCfa.61.

Genome annotation databases

EnsembliENSCAFT00000032279; ENSCAFP00000030061; ENSCAFG00000020263. [Q8HZR1-3]
ENSCAFT00000032287; ENSCAFP00000030067; ENSCAFG00000020263. [Q8HZR1-1]
GeneIDi403544.
KEGGicfa:403544.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF535138 mRNA. Translation: AAN33049.1 .
AF535139 mRNA. Translation: AAN38739.1 .
AAEX03006907 Genomic DNA. No translation available.
RefSeqi NP_001003023.1. NM_001003023.2.
UniGenei Cfa.61.

3D structure databases

ProteinModelPortali Q8HZR1.
ModBasei Search...
MobiDBi Search...

Chemistry

ChEMBLi CHEMBL4133.

Protein family/group databases

PeroxiBasei 3362. CfaPGHS01.

Proteomic databases

PaxDbi Q8HZR0.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSCAFT00000032279 ; ENSCAFP00000030061 ; ENSCAFG00000020263 . [Q8HZR1-3 ]
ENSCAFT00000032287 ; ENSCAFP00000030067 ; ENSCAFG00000020263 . [Q8HZR1-1 ]
GeneIDi 403544.
KEGGi cfa:403544.

Organism-specific databases

CTDi 5742.

Phylogenomic databases

eggNOGi NOG39991.
GeneTreei ENSGT00390000010743.
HOGENOMi HOG000013149.
HOVERGENi HBG000366.
InParanoidi Q8HZR1.
KOi K00509.

Enzyme and pathway databases

UniPathwayi UPA00662 .
Reactomei REACT_174506. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).

Miscellaneous databases

NextBioi 20817054.

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

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiPGH1_CANFA
AccessioniPrimary (citable) accession number: Q8HZR1
Secondary accession number(s): F1PBX3, Q8HZR0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 14, 2014
Last sequence update: May 14, 2014
Last modified: September 3, 2014
This is version 88 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

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