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Q8HZR1

- PGH1_CANFA

UniProt

Q8HZR1 - PGH1_CANFA

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Protein

Prostaglandin G/H synthase 1

Gene

PTGS1

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).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 acceptorPROSITE-ProRule annotation
Active sitei388 – 3881For cyclooxygenase activityBy similarity
Metal bindingi391 – 3911Iron (heme axial ligand)PROSITE-ProRule annotation
Sitei533 – 5331Aspirin-acetylated serineBy 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. cyclooxygenase pathway Source: InterPro
  2. inflammatory response Source: InterPro
  3. regulation of blood pressure Source: InterPro
  4. 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 1 Publication. Endoplasmic reticulum membrane 1 Publication; Peripheral membrane protein 1 Publication

GO - Cellular componenti

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

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

Amino acid modifications

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 7339EGF-likePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the prostaglandin G/H synthase family.Curated
Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal

Phylogenomic databases

eggNOGiNOG39991.
GeneTreeiENSGT00390000010743.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
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

        10         20         30         40         50
MSRGSRLHRW PLLLLLLLLL PPPPVLPAEA RTPAPVNPCC YYPCQHQGIC
60 70 80 90 100
VRFGLDRYQC DCTRTGYSGP NCTIPELWTW LRNSLRPSPS FLHFLLTHGR
110 120 130 140 150
WFWEFINATF IRDMLMRLVL TARSNLIPSP PTYNIAHDYI SWESFSNVSY
160 170 180 190 200
YTRVLPSVPQ DCPTPMGTKG KKQLPDAQLL GRRFLLRRKF IPDPQGTNLM
210 220 230 240 250
FAFFAQHFTH QFFKTSGKMG PGFTKALGHG VDLGHIYGDN LDRQYQLRLF
260 270 280 290 300
KDGKLKYQVL DGEMYPPSVE EAPVLMHYPR GILPQSQMAV GQEVFGLLPG
310 320 330 340 350
LMLYATLWLR EHNRVCDLLK AEHPTWGDEQ LFQTARLILI GETIKIVIEE
360 370 380 390 400
YVQQLSGYFL QLKFDPELLF SAQFQYRNRI AMEFNQLYHW HPLMPDSFWV
410 420 430 440 450
GSQEYSYEQF LFNTSMLTHY GIEALVDAFS RQSAGRIGGG RNIDHHVLHV
460 470 480 490 500
AVETIKESRE LRLQPFNEYR KRFGMRPYMS FQELTGEKEM AAELEELYGD
510 520 530 540 550
IDALEFYPGL LLEKCHPNSI FGESMIEIGA PFSLKGLLGN PICSPEYWKP
560 570 580 590 600
STFGGEMGFN MVKTATLKKL VCLNTKTCPY VSFRVPDPHQ DGGPGVERPS

TEL
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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti597 – 5971E → Q in AAN33049. (PubMed:12242329)Curated
Sequence conflicti597 – 5971E → Q in AAN38739. (PubMed:12242329)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei3 – 31R → REFDPEAPRNPLRLPGEPRM PGPALTSRSAG in isoform 2 and isoform 3. 1 PublicationVSP_054856
Alternative sequencei122 – 340219Missing in isoform 3 and isoform 4. 1 PublicationVSP_054857Add
BLAST

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

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.
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: October 29, 2014
This is version 90 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