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Protein

Prostaglandin G/H synthase 1

Gene

PTGS1

Organism
Ovis aries (Sheep)
Status
Reviewed-Annotation score: 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.1 Publication

Catalytic activityi

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

Cofactori

heme bNote: Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.

Pathwayi: prostaglandin biosynthesis

This protein is involved in the pathway prostaglandin biosynthesis, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway prostaglandin biosynthesis and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei207Proton acceptor1
Active sitei385For cyclooxygenase activity1 Publication1
Metal bindingi388Iron (heme axial ligand)1
Sitei530Aspirin-acetylated serine1

GO - Molecular functioni

GO - Biological processi

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

BRENDAi1.14.99.1. 2668.
SABIO-RKP05979.
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei4121. OarPGHS01.

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
OrganismiOvis aries (Sheep)
Taxonomic identifieri9940 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis
Proteomesi
  • UP000002356 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei74 – 82Helical9
Transmembranei86 – 92Helical7
Transmembranei97 – 105Helical9
Transmembranei108 – 122HelicalAdd BLAST15

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi385Y → F: Abolishes cyclooxygenase activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2949.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Add BLAST24
ChainiPRO_000002387125 – 600Prostaglandin G/H synthase 1Add BLAST576

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi36 ↔ 47
Disulfide bondi37 ↔ 159
Disulfide bondi41 ↔ 57
Disulfide bondi59 ↔ 69
Glycosylationi68N-linked (GlcNAc...)1 Publication1
Glycosylationi144N-linked (GlcNAc...)1 Publication1
Glycosylationi410N-linked (GlcNAc...)1 Publication1
Disulfide bondi569 ↔ 575

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei104Not glycosylated1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP05979.

Interactioni

Subunit structurei

Homodimer.

Chemistry databases

BindingDBiP05979.

Structurei

Secondary structure

1600
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi35 – 38Combined sources4
Beta strandi46 – 50Combined sources5
Turni51 – 53Combined sources3
Beta strandi54 – 58Combined sources5
Beta strandi62 – 65Combined sources4
Turni66 – 69Combined sources4
Helixi74 – 82Combined sources9
Helixi86 – 93Combined sources8
Helixi97 – 103Combined sources7
Helixi108 – 121Combined sources14
Beta strandi130 – 133Combined sources4
Beta strandi134 – 136Combined sources3
Helixi139 – 143Combined sources5
Beta strandi149 – 152Combined sources4
Beta strandi159 – 161Combined sources3
Beta strandi164 – 167Combined sources4
Helixi174 – 181Combined sources8
Helixi196 – 206Combined sources11
Turni207 – 209Combined sources3
Turni214 – 216Combined sources3
Beta strandi220 – 222Combined sources3
Beta strandi227 – 229Combined sources3
Helixi231 – 234Combined sources4
Helixi238 – 244Combined sources7
Beta strandi255 – 257Combined sources3
Beta strandi260 – 262Combined sources3
Turni266 – 268Combined sources3
Helixi281 – 283Combined sources3
Beta strandi288 – 291Combined sources4
Helixi292 – 294Combined sources3
Helixi296 – 319Combined sources24
Helixi325 – 346Combined sources22
Helixi348 – 353Combined sources6
Helixi363 – 366Combined sources4
Beta strandi367 – 369Combined sources3
Helixi379 – 384Combined sources6
Helixi388 – 390Combined sources3
Beta strandi393 – 397Combined sources5
Beta strandi400 – 402Combined sources3
Helixi404 – 407Combined sources4
Helixi413 – 417Combined sources5
Helixi419 – 428Combined sources10
Beta strandi434 – 438Combined sources5
Turni442 – 444Combined sources3
Helixi445 – 457Combined sources13
Helixi463 – 469Combined sources7
Helixi478 – 482Combined sources5
Beta strandi483 – 485Combined sources3
Helixi486 – 495Combined sources10
Helixi498 – 500Combined sources3
Helixi503 – 509Combined sources7
Beta strandi517 – 519Combined sources3
Helixi520 – 535Combined sources16
Helixi538 – 540Combined sources3
Turni542 – 544Combined sources3
Helixi547 – 550Combined sources4
Helixi553 – 560Combined sources8
Helixi564 – 569Combined sources6
Beta strandi572 – 574Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CQEX-ray3.10A/B21-600[»]
1DIYX-ray3.00A32-584[»]
1DJJmodel-A25-600[»]
1EBVX-ray3.20A33-583[»]
1EQGX-ray2.61A/B21-600[»]
1EQHX-ray2.70A/B21-600[»]
1FE2X-ray3.00A25-600[»]
1HT5X-ray2.75A/B33-583[»]
1HT8X-ray2.69A/B33-583[»]
1IGXX-ray3.10A25-600[»]
1IGZX-ray2.90A25-600[»]
1PGEX-ray3.50A/B25-600[»]
1PGFX-ray4.50A/B25-600[»]
1PGGX-ray4.50A/B25-600[»]
1PRHX-ray3.50A/B33-586[»]
1PTHX-ray3.40A/B25-600[»]
1Q4GX-ray2.00A/B32-584[»]
1U67X-ray3.10A1-600[»]
2AYLX-ray2.00A/B32-584[»]
2OYEX-ray2.85P1-600[»]
2OYUX-ray2.70P1-600[»]
3KK6X-ray2.75A/B32-584[»]
3N8VX-ray3.05A/B32-584[»]
3N8WX-ray2.75A/B32-584[»]
3N8XX-ray2.75A/B32-584[»]
3N8YX-ray2.60A/B32-584[»]
3N8ZX-ray2.90A/B32-584[»]
4O1ZX-ray2.40A/B32-600[»]
SMRiP05979.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05979.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 70EGF-likePROSITE-ProRule annotationAdd BLAST39

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, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG000366.
KOiK00509.

Family and domain databases

Gene3Di1.10.640.10. 1 hit.
InterProiIPR029580. COX-1.
IPR000742. EGF-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view]
PANTHERiPTHR11903:SF6. PTHR11903:SF6. 1 hit.
PfamiPF03098. An_peroxidase. 1 hit.
PF00008. EGF. 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.

P05979-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRQSISLRF PLLLLLLSPS PVFSADPGAP APVNPCCYYP CQHQGICVRF
60 70 80 90 100
GLDRYQCDCT RTGYSGPNCT IPEIWTWLRT TLRPSPSFIH FLLTHGRWLW
110 120 130 140 150
DFVNATFIRD TLMRLVLTVR SNLIPSPPTY NIAHDYISWE SFSNVSYYTR
160 170 180 190 200
ILPSVPRDCP TPMDTKGKKQ LPDAEFLSRR FLLRRKFIPD PQSTNLMFAF
210 220 230 240 250
FAQHFTHQFF KTSGKMGPGF TKALGHGVDL GHIYGDNLER QYQLRLFKDG
260 270 280 290 300
KLKYQMLNGE VYPPSVEEAP VLMHYPRGIP PQSQMAVGQE VFGLLPGLML
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
VIKESRVLRL QPFNEYRKRF GMKPYTSFQE LTGEKEMAAE LEELYGDIDA
510 520 530 540 550
LEFYPGLLLE KCHPNSIFGE SMIEMGAPFS LKGLLGNPIC SPEYWKASTF
560 570 580 590 600
GGEVGFNLVK TATLKKLVCL NTKTCPYVSF HVPDPRQEDR PGVERPPTEL
Length:600
Mass (Da):68,861
Last modified:February 4, 2015 - v3
Checksum:i809887C7BB5A715C
GO

Sequence cautioni

The sequence AAA31576 differs from that shown. Reason: Frameshift at positions 63 and 92.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 5MSRQS → MVQG in AAA31511 (PubMed:2831188).Curated5
Sequence conflicti193S → G in AAA31576 (PubMed:3125548).Curated1
Sequence conflicti193S → G in AAA31511 (PubMed:2831188).Curated1
Sequence conflicti540C → E AA sequence (PubMed:6414516).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti97R → H.1
Natural varianti164D → G.2 Publications1
Natural varianti456R → Q.1
Natural varianti520E → K.1
Natural varianti520E → Q.1
Natural varianti525M → I.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03599 mRNA. Translation: AAA31576.1. Frameshift.
Y00750 mRNA. Translation: CAA68719.1.
M18243 mRNA. Translation: AAA31511.1.
PIRiA28960.
A29947.
S00561.
RefSeqiNP_001009476.1. NM_001009476.1.
UniGeneiOar.445.

Genome annotation databases

GeneIDi443551.
KEGGioas:443551.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03599 mRNA. Translation: AAA31576.1. Frameshift.
Y00750 mRNA. Translation: CAA68719.1.
M18243 mRNA. Translation: AAA31511.1.
PIRiA28960.
A29947.
S00561.
RefSeqiNP_001009476.1. NM_001009476.1.
UniGeneiOar.445.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CQEX-ray3.10A/B21-600[»]
1DIYX-ray3.00A32-584[»]
1DJJmodel-A25-600[»]
1EBVX-ray3.20A33-583[»]
1EQGX-ray2.61A/B21-600[»]
1EQHX-ray2.70A/B21-600[»]
1FE2X-ray3.00A25-600[»]
1HT5X-ray2.75A/B33-583[»]
1HT8X-ray2.69A/B33-583[»]
1IGXX-ray3.10A25-600[»]
1IGZX-ray2.90A25-600[»]
1PGEX-ray3.50A/B25-600[»]
1PGFX-ray4.50A/B25-600[»]
1PGGX-ray4.50A/B25-600[»]
1PRHX-ray3.50A/B33-586[»]
1PTHX-ray3.40A/B25-600[»]
1Q4GX-ray2.00A/B32-584[»]
1U67X-ray3.10A1-600[»]
2AYLX-ray2.00A/B32-584[»]
2OYEX-ray2.85P1-600[»]
2OYUX-ray2.70P1-600[»]
3KK6X-ray2.75A/B32-584[»]
3N8VX-ray3.05A/B32-584[»]
3N8WX-ray2.75A/B32-584[»]
3N8XX-ray2.75A/B32-584[»]
3N8YX-ray2.60A/B32-584[»]
3N8ZX-ray2.90A/B32-584[»]
4O1ZX-ray2.40A/B32-600[»]
SMRiP05979.
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

BindingDBiP05979.
ChEMBLiCHEMBL2949.

Protein family/group databases

PeroxiBasei4121. OarPGHS01.

Proteomic databases

PRIDEiP05979.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi443551.
KEGGioas:443551.

Organism-specific databases

CTDi5742.

Phylogenomic databases

HOVERGENiHBG000366.
KOiK00509.

Enzyme and pathway databases

UniPathwayiUPA00662.
BRENDAi1.14.99.1. 2668.
SABIO-RKP05979.

Miscellaneous databases

EvolutionaryTraceiP05979.
PROiP05979.

Family and domain databases

Gene3Di1.10.640.10. 1 hit.
InterProiIPR029580. COX-1.
IPR000742. EGF-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view]
PANTHERiPTHR11903:SF6. PTHR11903:SF6. 1 hit.
PfamiPF03098. An_peroxidase. 1 hit.
PF00008. EGF. 1 hit.
[Graphical view]
PRINTSiPR00457. ANPEROXIDASE.
SUPFAMiSSF48113. SSF48113. 1 hit.
PROSITEiPS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPGH1_SHEEP
AccessioniPrimary (citable) accession number: P05979
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 4, 2015
Last modified: November 2, 2016
This is version 151 of the entry and version 3 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.