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P35354

- PGH2_HUMAN

UniProt

P35354 - PGH2_HUMAN

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Protein
Prostaglandin G/H synthase 2
Gene
PTGS2, COX2
Organism
Homo sapiens (Human)
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. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.1 Publication

Catalytic activityi

Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O.1 Publication

Cofactori

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

Kineticsi

  1. KM=16.2 µM for arachidonate (in absence of sodium nitroprusside NO donor)1 Publication
  2. KM=17.0 µM for arachidonate (in presence of sodium nitroprusside NO donor)

Vmax=81.3 nmol/min/mg enzyme (in absence of sodium nitroprusside NO donor)

Vmax=132 nmol/min/mg enzyme (in absence of sodium nitroprusside NO donor)

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei106 – 1061Substrate By similarity
Active sitei193 – 1931Proton acceptor By similarity
Binding sitei341 – 3411Substrate By similarity
Active sitei371 – 3711For cyclooxygenase activity By similarity
Binding sitei371 – 3711Substrate By similarity
Metal bindingi374 – 3741Iron (heme axial ligand) By similarity
Sitei516 – 5161Aspirin-acetylated serine By similarity

GO - Molecular functioni

  1. arachidonate 15-lipoxygenase activity Source: Reactome
  2. enzyme binding Source: UniProtKB
  3. heme binding Source: UniProtKB
  4. lipid binding Source: Ensembl
  5. metal ion binding Source: UniProtKB-KW
  6. peroxidase activity Source: UniProtKB
  7. prostaglandin-endoperoxide synthase activity Source: UniProtKB

GO - Biological processi

  1. anagen Source: Ensembl
  2. angiogenesis Source: Ensembl
  3. arachidonic acid metabolic process Source: Reactome
  4. bone mineralization Source: Ensembl
  5. brown fat cell differentiation Source: Ensembl
  6. cellular component movement Source: ProtInc
  7. cellular response to ATP Source: Ensembl
  8. cellular response to UV Source: Ensembl
  9. cellular response to hypoxia Source: UniProtKB
  10. cellular response to mechanical stimulus Source: Ensembl
  11. cyclooxygenase pathway Source: BHF-UCL
  12. decidualization Source: Ensembl
  13. embryo implantation Source: Ensembl
  14. inflammatory response Source: Ensembl
  15. learning Source: Ensembl
  16. lipoxygenase pathway Source: Reactome
  17. maintenance of blood-brain barrier Source: Ensembl
  18. memory Source: Ensembl
  19. negative regulation of calcium ion transport Source: Ensembl
  20. negative regulation of cell cycle Source: Ensembl
  21. negative regulation of cell proliferation Source: Ensembl
  22. negative regulation of smooth muscle contraction Source: Ensembl
  23. negative regulation of synaptic transmission, dopaminergic Source: Ensembl
  24. ovulation Source: Ensembl
  25. positive regulation of NF-kappaB import into nucleus Source: Ensembl
  26. positive regulation of apoptotic process Source: Ensembl
  27. positive regulation of brown fat cell differentiation Source: BHF-UCL
  28. positive regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
  29. positive regulation of fever generation Source: BHF-UCL
  30. positive regulation of fibroblast growth factor production Source: BHF-UCL
  31. positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
  32. positive regulation of platelet-derived growth factor production Source: BHF-UCL
  33. positive regulation of prostaglandin biosynthetic process Source: BHF-UCL
  34. positive regulation of smooth muscle cell proliferation Source: Ensembl
  35. positive regulation of smooth muscle contraction Source: Ensembl
  36. positive regulation of synaptic plasticity Source: Ensembl
  37. positive regulation of synaptic transmission, glutamatergic Source: Ensembl
  38. positive regulation of transforming growth factor beta production Source: BHF-UCL
  39. positive regulation of vasoconstriction Source: Ensembl
  40. positive regulation vascular endothelial growth factor production Source: BHF-UCL
  41. prostaglandin biosynthetic process Source: UniProtKB
  42. prostaglandin metabolic process Source: ProtInc
  43. regulation of blood pressure Source: UniProtKB
  44. regulation of inflammatory response Source: UniProtKB
  45. response to drug Source: Ensembl
  46. response to estradiol Source: Ensembl
  47. response to fatty acid Source: Ensembl
  48. response to fructose Source: Ensembl
  49. response to glucocorticoid Source: Ensembl
  50. response to lipopolysaccharide Source: Ensembl
  51. response to lithium ion Source: Ensembl
  52. response to manganese ion Source: Ensembl
  53. response to oxidative stress Source: InterPro
  54. response to tumor necrosis factor Source: Ensembl
  55. response to vitamin D Source: Ensembl
  56. sensory perception of pain Source: Ensembl
  57. small molecule metabolic process Source: Reactome
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

BioCyciMetaCyc:HS01115-MONOMER.
BRENDAi1.14.99.1. 2681.
ReactomeiREACT_150149. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_150422. Synthesis of 15-eicosatetraenoic acid derivatives.
SABIO-RKP35354.
UniPathwayiUPA00662.

Protein family/group databases

PeroxiBasei3321. HsPGHS02.

Names & Taxonomyi

Protein namesi
Recommended name:
Prostaglandin G/H synthase 2 (EC:1.14.99.1)
Alternative name(s):
Cyclooxygenase-2
Short name:
COX-2
PHS II
Prostaglandin H2 synthase 2
Short name:
PGH synthase 2
Short name:
PGHS-2
Prostaglandin-endoperoxide synthase 2
Gene namesi
Name:PTGS2
Synonyms:COX2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:9605. PTGS2.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. endoplasmic reticulum membrane Source: Reactome
  3. neuron projection Source: MGI
  4. nucleus Source: UniProtKB
  5. protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi526 – 5261C → S: Prevents activation by nitric oxid (NO). 1 Publication
Mutagenesisi555 – 5551C → S: Abolishes enzyme activity. 1 Publication
Mutagenesisi561 – 5611C → S: Does not affect activation by nitric oxid (NO). 1 Publication

Organism-specific databases

PharmGKBiPA293.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717 Reviewed prediction
Add
BLAST
Chaini18 – 604587Prostaglandin G/H synthase 2
PRO_0000023875Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi21 ↔ 32 By similarity
Disulfide bondi22 ↔ 145 By similarity
Disulfide bondi26 ↔ 42 By similarity
Disulfide bondi44 ↔ 54 By similarity
Glycosylationi53 – 531N-linked (GlcNAc...) Reviewed prediction
Glycosylationi130 – 1301N-linked (GlcNAc...) Reviewed prediction
Glycosylationi396 – 3961N-linked (GlcNAc...) Reviewed prediction
Modified residuei526 – 5261S-nitrosocysteine Inferred
Disulfide bondi555 ↔ 561 By similarity
Glycosylationi580 – 5801N-linked (GlcNAc...)1 Publication

Post-translational modificationi

S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526.

Keywords - PTMi

Disulfide bond, Glycoprotein, S-nitrosylation

Proteomic databases

MaxQBiP35354.
PaxDbiP35354.
PRIDEiP35354.

PTM databases

PhosphoSiteiP35354.

Expressioni

Inductioni

By cytokines and mitogens.

Gene expression databases

ArrayExpressiP35354.
BgeeiP35354.
CleanExiHS_PTGS2.
GenevestigatoriP35354.

Organism-specific databases

HPAiCAB000113.
HPA001335.

Interactioni

Subunit structurei

Homodimer By similarity.

Protein-protein interaction databases

BioGridi111715. 27 interactions.
DIPiDIP-28131N.
IntActiP35354. 2 interactions.
MINTiMINT-203337.
STRINGi9606.ENSP00000356438.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1V0Xmodel-A1-604[»]
ProteinModelPortaliP35354.
SMRiP35354. Positions 18-568.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 5538EGF-like
Add
BLAST

Sequence similaritiesi

Contains 1 EGF-like domain.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG39991.
HOGENOMiHOG000013149.
HOVERGENiHBG000366.
InParanoidiP35354.
KOiK11987.
OMAiICNNVKG.
OrthoDBiEOG7RFTHC.
PhylomeDBiP35354.
TreeFamiTF329675.

Family and domain databases

Gene3Di1.10.640.10. 1 hit.
InterProiIPR029576. COX-2.
IPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view]
PANTHERiPTHR11903:SF8. PTHR11903:SF8. 1 hit.
PfamiPF03098. An_peroxidase. 1 hit.
[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]

Sequencei

Sequence statusi: Complete.

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

P35354-1 [UniParc]FASTAAdd to Basket

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MLARALLLCA VLALSHTANP CCSHPCQNRG VCMSVGFDQY KCDCTRTGFY    50
GENCSTPEFL TRIKLFLKPT PNTVHYILTH FKGFWNVVNN IPFLRNAIMS 100
YVLTSRSHLI DSPPTYNADY GYKSWEAFSN LSYYTRALPP VPDDCPTPLG 150
VKGKKQLPDS NEIVEKLLLR RKFIPDPQGS NMMFAFFAQH FTHQFFKTDH 200
KRGPAFTNGL GHGVDLNHIY GETLARQRKL RLFKDGKMKY QIIDGEMYPP 250
TVKDTQAEMI YPPQVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD 300
VLKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE 350
LLFNKQFQYQ NRIAAEFNTL YHWHPLLPDT FQIHDQKYNY QQFIYNNSIL 400
LEHGITQFVE SFTRQIAGRV AGGRNVPPAV QKVSQASIDQ SRQMKYQSFN 450
EYRKRFMLKP YESFEELTGE KEMSAELEAL YGDIDAVELY PALLVEKPRP 500
DAIFGETMVE VGAPFSLKGL MGNVICSPAY WKPSTFGGEV GFQIINTASI 550
QSLICNNVKG CPFTSFSVPD PELIKTVTIN ASSSRSGLDD INPTVLLKER 600
STEL 604
Length:604
Mass (Da):68,996
Last modified:December 15, 1998 - v2
Checksum:i72FBD699F6128519
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti228 – 2281R → H.1 Publication
Corresponds to variant rs3218622 [ dbSNP | Ensembl ].
VAR_016262
Natural varianti428 – 4281P → A.1 Publication
Corresponds to variant rs4648279 [ dbSNP | Ensembl ].
VAR_016263
Natural varianti488 – 4881E → G.
Corresponds to variant rs5272 [ dbSNP | Ensembl ].
VAR_011980
Natural varianti511 – 5111V → A.2 Publications
Corresponds to variant rs5273 [ dbSNP | Ensembl ].
VAR_011981
Natural varianti587 – 5871G → R.1 Publication
Corresponds to variant rs3218625 [ dbSNP | Ensembl ].
VAR_016264

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti165 – 1651E → G in AAA58433. 1 Publication
Sequence conflicti438 – 4381I → T in AAA35803. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L15326 mRNA. Translation: AAA35803.1.
M90100 mRNA. Translation: AAA58433.1.
D28235 Genomic DNA. Translation: BAA05698.1.
U04636 Genomic DNA. Translation: AAA57317.1.
AY462100 mRNA. Translation: AAR23927.1.
AY229989 Genomic DNA. Translation: AAO38056.1.
AY382629 Genomic DNA. Translation: AAQ75702.1.
AK292167 mRNA. Translation: BAF84856.1.
AL033533 Genomic DNA. Translation: CAB41240.1.
CH471067 Genomic DNA. Translation: EAW91216.1.
BC013734 mRNA. Translation: AAH13734.1.
CCDSiCCDS1371.1.
PIRiA46150.
RefSeqiNP_000954.1. NM_000963.3.
UniGeneiHs.196384.

Genome annotation databases

EnsembliENST00000367468; ENSP00000356438; ENSG00000073756.
GeneIDi5743.
KEGGihsa:5743.
UCSCiuc001gsb.3. human.

Polymorphism databases

DMDMi3915797.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L15326 mRNA. Translation: AAA35803.1 .
M90100 mRNA. Translation: AAA58433.1 .
D28235 Genomic DNA. Translation: BAA05698.1 .
U04636 Genomic DNA. Translation: AAA57317.1 .
AY462100 mRNA. Translation: AAR23927.1 .
AY229989 Genomic DNA. Translation: AAO38056.1 .
AY382629 Genomic DNA. Translation: AAQ75702.1 .
AK292167 mRNA. Translation: BAF84856.1 .
AL033533 Genomic DNA. Translation: CAB41240.1 .
CH471067 Genomic DNA. Translation: EAW91216.1 .
BC013734 mRNA. Translation: AAH13734.1 .
CCDSi CCDS1371.1.
PIRi A46150.
RefSeqi NP_000954.1. NM_000963.3.
UniGenei Hs.196384.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1V0X model - A 1-604 [» ]
ProteinModelPortali P35354.
SMRi P35354. Positions 18-568.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111715. 27 interactions.
DIPi DIP-28131N.
IntActi P35354. 2 interactions.
MINTi MINT-203337.
STRINGi 9606.ENSP00000356438.

Chemistry

BindingDBi P35354.
ChEMBLi CHEMBL230.
DrugBanki DB00316. Acetaminophen.
DB00945. Aspirin.
DB01014. Balsalazide.
DB00963. Bromfenac.
DB00821. Carprofen.
DB00482. Celecoxib.
DB01188. Ciclopirox.
DB00586. Diclofenac.
DB00861. Diflunisal.
DB01240. Epoprostenol.
DB00749. Etodolac.
DB01628. Etoricoxib.
DB00573. Fenoprofen.
DB00712. Flurbiprofen.
DB00154. gamma-Homolinolenic acid.
DB01404. Ginseng.
DB01050. Ibuprofen.
DB00159. Icosapent.
DB00328. Indomethacin.
DB01009. Ketoprofen.
DB00465. Ketorolac.
DB00480. Lenalidomide.
DB01283. Lumiracoxib.
DB00939. Meclofenamic acid.
DB00784. Mefenamic acid.
DB00814. Meloxicam.
DB00244. Mesalazine.
DB00461. Nabumetone.
DB00788. Naproxen.
DB00991. Oxaprozin.
DB00812. Phenylbutazone.
DB00533. Rofecoxib.
DB00936. Salicyclic acid.
DB01399. Salsalate.
DB00605. Sulindac.
DB00870. Suprofen.
DB00469. Tenoxicam.
DB01041. Thalidomide.
DB01600. Tiaprofenic acid.
DB00500. Tolmetin.
DB00580. Valdecoxib.
GuidetoPHARMACOLOGYi 1376.

Protein family/group databases

PeroxiBasei 3321. HsPGHS02.

PTM databases

PhosphoSitei P35354.

Polymorphism databases

DMDMi 3915797.

Proteomic databases

MaxQBi P35354.
PaxDbi P35354.
PRIDEi P35354.

Protocols and materials databases

DNASUi 5743.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000367468 ; ENSP00000356438 ; ENSG00000073756 .
GeneIDi 5743.
KEGGi hsa:5743.
UCSCi uc001gsb.3. human.

Organism-specific databases

CTDi 5743.
GeneCardsi GC01M186640.
HGNCi HGNC:9605. PTGS2.
HPAi CAB000113.
HPA001335.
MIMi 600262. gene.
neXtProti NX_P35354.
PharmGKBi PA293.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG39991.
HOGENOMi HOG000013149.
HOVERGENi HBG000366.
InParanoidi P35354.
KOi K11987.
OMAi ICNNVKG.
OrthoDBi EOG7RFTHC.
PhylomeDBi P35354.
TreeFami TF329675.

Enzyme and pathway databases

UniPathwayi UPA00662 .
BioCyci MetaCyc:HS01115-MONOMER.
BRENDAi 1.14.99.1. 2681.
Reactomei REACT_150149. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_150422. Synthesis of 15-eicosatetraenoic acid derivatives.
SABIO-RK P35354.

Miscellaneous databases

GeneWikii Prostaglandin-endoperoxide_synthase_2.
PTGS2.
GenomeRNAii 5743.
NextBioi 22358.
PROi P35354.
SOURCEi Search...

Gene expression databases

ArrayExpressi P35354.
Bgeei P35354.
CleanExi HS_PTGS2.
Genevestigatori P35354.

Family and domain databases

Gene3Di 1.10.640.10. 1 hit.
InterProi IPR029576. COX-2.
IPR000742. EG-like_dom.
IPR010255. Haem_peroxidase.
IPR019791. Haem_peroxidase_animal.
[Graphical view ]
PANTHERi PTHR11903:SF8. PTHR11903:SF8. 1 hit.
Pfami PF03098. An_peroxidase. 1 hit.
[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. "Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines."
    Jones D.A., Carlton D.P., McIntyre T.M., Zimmerman G.A., Prescott S.M.
    J. Biol. Chem. 268:9049-9054(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Endothelial cell.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Endothelial cell.
  3. "Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2."
    Kosaka T., Miyata A., Ihara H., Hara S., Sugimoto T., Takeda O., Takahashi E., Tanabe T.
    Eur. J. Biochem. 221:889-897(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Peripheral blood.
  4. "Structure of the human cyclo-oxygenase-2 gene."
    Appleby S.B., Ristimaki A., Neilson K., Narko K., Hla T.
    Biochem. J. 302:723-727(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Placenta.
  5. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Sharma S.V., Aronstam R.S.
    Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.
  6. NIEHS SNPs program
    Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-228; ALA-428; ALA-511 AND ARG-587.
  7. SeattleSNPs variation discovery resource
    Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  8. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Synovium.
  9. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  11. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Lung.
  12. "Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system."
    Barnett J., Chow J., Ives D., Chiou M., Mackenzie R., Osen E., Nguyen B., Tsing S., Bach C., Freire J.
    Biochim. Biophys. Acta 1209:130-139(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  13. "Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2."
    Kim S.F., Huri D.A., Snyder S.H.
    Science 310:1966-1970(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, S-NITROSYLATION AT CYS-526, MUTAGENESIS OF CYS-526; CYS-555 AND CYS-561.
  14. "Glycosylation regulates turnover of cyclooxygenase-2."
    Sevigny M.B., Li C.F., Alas M., Hughes-Fulford M.
    FEBS Lett. 580:6533-6536(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT ASN-580.
  15. "Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk."
    Goodman J.E., Bowman E.D., Chanock S.J., Alberg A.J., Harris C.C.
    Carcinogenesis 25:2467-2472(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ALA-511.
  16. "Cyclooxygenases: structural, cellular, and molecular biology."
    Smith W.L., DeWitt D.L., Garavito R.M.
    Annu. Rev. Biochem. 69:145-182(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION; TISSUE SPECIFICITY AND INHIBITION BY NSAIDS.
  17. "Aspirin, cyclooxygenase inhibition and colorectal cancer."
    Sostres C., Gargallo C.J., Lanas A.
    World J. Gastrointest. Pharmacol. Ther. 5:40-49(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION; INHIBITION BY ASPIRIN AND INVOLVEMENT IN COLORECTAL CANCER.

Entry informationi

Entry nameiPGH2_HUMAN
AccessioniPrimary (citable) accession number: P35354
Secondary accession number(s): A8K802, Q16876
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: December 15, 1998
Last modified: September 3, 2014
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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