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O62664

- PGH1_BOVIN

UniProt

O62664 - PGH1_BOVIN

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Protein

Prostaglandin G/H synthase 1

Gene

PTGS1

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript 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 sitei207 – 2071Proton acceptorPROSITE-ProRule annotation
Active sitei385 – 3851For cyclooxygenase activityBy similarity
Metal bindingi388 – 3881Iron (heme axial ligand)PROSITE-ProRule annotation
Sitei530 – 5301Aspirin-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: Ensembl
  2. inflammatory response Source: InterPro
  3. regulation of blood pressure Source: Ensembl
  4. regulation of cell proliferation Source: Ensembl
  5. 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_214914. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_222361. COX reactions.
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei3332. BtPGHS01.

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:COX-1, COX1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136: Chromosome 11

Subcellular locationi

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB-KW
  2. membrane Source: UniProtKB-KW
  3. photoreceptor outer segment Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 600576Prostaglandin G/H synthase 1PRO_0000163113Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi36 ↔ 47By similarity
Disulfide bondi37 ↔ 159By similarity
Disulfide bondi41 ↔ 57By similarity
Disulfide bondi59 ↔ 69By similarity
Glycosylationi68 – 681N-linked (GlcNAc...)Sequence Analysis
Glycosylationi104 – 1041N-linked (GlcNAc...)Sequence Analysis
Glycosylationi144 – 1441N-linked (GlcNAc...)Sequence Analysis
Glycosylationi410 – 4101N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi569 ↔ 575By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homodimer.By similarity

Structurei

3D structure databases

ProteinModelPortaliO62664.
SMRiO62664. Positions 32-584.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 7039EGF-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.
InParanoidiO62664.
KOiK00509.
OMAiFKTSGKM.
OrthoDBiEOG7RFTHC.
TreeFamiTF329675.

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. 1 hit.
[Graphical view]
PRINTSiPR00457. ANPEROXIDASE.
SUPFAMiSSF48113. SSF48113. 1 hit.
PROSITEiPS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

O62664-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSRQGISLRF PLLLLLLSPS PVLPADPGAP APVNPCCYYP CQHQGICVRF
60 70 80 90 100
GLDRYQCDCT RTGYYGPNCT IPEIWTWLRT TLRPSPSFVH FLLTHGRWLW
110 120 130 140 150
DFVNATFIRD KLMRLVLTVR SNLIPSPPTY NVAHDYISWE SFSNVSYYTR
160 170 180 190 200
ILPSVPRDCP TPMGTKGKKQ LPDAEFLSRR FLLRRKFIPD PQGTNLMFAF
210 220 230 240 250
FAQHFTHQFF KTSGKMGPGF TKALGHGVDL GHIYGDNLER QYQLRLFKDG
260 270 280 290 300
KLKYQMLNGE VYPPSVEEAP VLMHYPRGIP PQSQMAVGQE VFGLLPGLMV
310 320 330 340 350
YATIWLREHN RVCDLLKAEH PTWGDEQLFQ TARLILIGET IKIVIEEYVQ
360 370 380 390 400
QLSGYFLQLK FDPELLFGAQ FQYRNRIAME FNQLYHWHPL MPDSFRVGPQ
410 420 430 440 450
DYSYEQFLFN TSMLVDYGVE ALVDAFSRQP AGRIGGGRNI DHHILHVAVD
460 470 480 490 500
VIKESRELRL QPFNEYRKRF GMKPYTSFQE LTGEKEMAAE LEELYGDIDA
510 520 530 540 550
LEFYPGLLLE KCHPNSIFGE SMIEMGAPFS LKGLLGNPIC SPEYWKASTF
560 570 580 590 600
GGDVGFNLVK TATLKKLVCL NTKTCPYVSF HVPDPHREDR PGVERPPTEL
Length:600
Mass (Da):68,805
Last modified:February 5, 2008 - v2
Checksum:i0B43E65DA9E2A2E9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti229 – 2291D → G in AAC05591. (PubMed:9348208)Curated
Sequence conflicti241 – 2411Q → R in AAC05591. (PubMed:9348208)Curated
Sequence conflicti263 – 2631P → Q in AAC05591. (PubMed:9348208)Curated
Sequence conflicti320 – 3201H → Q in AAC05591. (PubMed:9348208)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC134517 mRNA. Translation: AAI34518.1.
AF004943 mRNA. Translation: AAC05591.1.
RefSeqiNP_001098793.1. NM_001105323.1.
UniGeneiBt.2151.

Genome annotation databases

EnsembliENSBTAT00000008833; ENSBTAP00000008833; ENSBTAG00000006716.
GeneIDi282022.
KEGGibta:282022.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC134517 mRNA. Translation: AAI34518.1 .
AF004943 mRNA. Translation: AAC05591.1 .
RefSeqi NP_001098793.1. NM_001105323.1.
UniGenei Bt.2151.

3D structure databases

ProteinModelPortali O62664.
SMRi O62664. Positions 32-584.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi O62664.
ChEMBLi CHEMBL2096674.

Protein family/group databases

PeroxiBasei 3332. BtPGHS01.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSBTAT00000008833 ; ENSBTAP00000008833 ; ENSBTAG00000006716 .
GeneIDi 282022.
KEGGi bta:282022.

Organism-specific databases

CTDi 5742.

Phylogenomic databases

eggNOGi NOG39991.
GeneTreei ENSGT00390000010743.
HOGENOMi HOG000013149.
HOVERGENi HBG000366.
InParanoidi O62664.
KOi K00509.
OMAi FKTSGKM.
OrthoDBi EOG7RFTHC.
TreeFami TF329675.

Enzyme and pathway databases

UniPathwayi UPA00662 .
Reactomei REACT_214914. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_222361. COX reactions.

Miscellaneous databases

NextBioi 20805886.

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. 1 hit.
[Graphical view ]
PRINTSi PR00457. ANPEROXIDASE.
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. 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.

Entry informationi

Entry nameiPGH1_BOVIN
AccessioniPrimary (citable) accession number: O62664
Secondary accession number(s): A7YWD4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: February 5, 2008
Last modified: October 29, 2014
This is version 118 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