P35354 (PGH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 131.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | 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 names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 604 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity. Ref.13 |
| Catalytic activity | Arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O. Ref.13 |
| Cofactor | Binds 1 heme B (iron-protoporphyrin IX) group per subunit By similarity. |
| Pathway | |
| Subunit structure | Homodimer By similarity. |
| Subcellular location | Microsome membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. |
| Induction | By cytokines and mitogens. |
| Post-translational modification | S-nitrosylation by NOS2 (iNOS) activates enzme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-561. |
| Miscellaneous | This enzyme acts both as a dioxygenase and as a peroxidase. This enzyme is the target of nonsteroidal anti-inflammatory drugs such as aspirin. |
| Sequence similarities | Belongs to the prostaglandin G/H synthase family. Contains 1 EGF-like domain. |
| Biophysicochemical properties | Kinetic parameters: KM=16.2 µM for arachidonate (in absence of sodium nitroprusside NO donor) Ref.13 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) |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 17 | 17 | Potential | ||||||||
| Chain | 18 – 604 | 587 | Prostaglandin G/H synthase 2 | PRO_0000023875 | |||||||
Regions | |||||||||||
| Domain | 18 – 55 | 38 | EGF-like | ||||||||
Sites | |||||||||||
| Active site | 193 | 1 | Proton acceptor By similarity | ||||||||
| Active site | 371 | 1 | For cyclooxygenase activity By similarity | ||||||||
| Metal binding | 374 | 1 | Iron (heme axial ligand) By similarity | ||||||||
| Site | 516 | 1 | Aspirin-acetylated serine By similarity | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 437 | 1 | Phosphoserine By similarity | ||||||||
| Modified residue | 446 | 1 | Phosphotyrosine By similarity | ||||||||
| Modified residue | 561 | 1 | S-nitrosocysteine Probable | ||||||||
| Glycosylation | 53 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 130 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 396 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 580 | 1 | N-linked (GlcNAc...) Ref.14 | ||||||||
| Disulfide bond | 21 ↔ 32 | By similarity | |||||||||
| Disulfide bond | 22 ↔ 145 | By similarity | |||||||||
| Disulfide bond | 26 ↔ 42 | By similarity | |||||||||
| Disulfide bond | 44 ↔ 54 | By similarity | |||||||||
| Disulfide bond | 555 ↔ 561 | By similarity | |||||||||
Natural variations | |||||||||||
| Natural variant | 228 | 1 | R → H. Ref.6 Corresponds to variant rs3218622 [ dbSNP | Ensembl ]. | VAR_016262 | |||||||
| Natural variant | 428 | 1 | P → A. Ref.6 Corresponds to variant rs4648279 [ dbSNP | Ensembl ]. | VAR_016263 | |||||||
| Natural variant | 488 | 1 | E → G. Corresponds to variant rs5272 [ dbSNP | Ensembl ]. | VAR_011980 | |||||||
| Natural variant | 511 | 1 | V → A. Ref.6 Ref.15 Corresponds to variant rs5273 [ dbSNP | Ensembl ]. | VAR_011981 | |||||||
| Natural variant | 587 | 1 | G → R. Ref.6 Corresponds to variant rs3218625 [ dbSNP | Ensembl ]. | VAR_016264 | |||||||
Experimental info | |||||||||||
| Mutagenesis | 526 | 1 | C → S: Prevents activation by nitric oxid (NO). Ref.13 | ||||||||
| Mutagenesis | 555 | 1 | C → S: Abolishes enzyme activity. Ref.13 | ||||||||
| Mutagenesis | 561 | 1 | C → S: Does not affect activation by nitric oxid (NO). Ref.13 | ||||||||
| Sequence conflict | 165 | 1 | E → G in AAA58433. Ref.2 | ||||||||
| Sequence conflict | 438 | 1 | I → T in AAA35803. Ref.1 | ||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [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: 8473346] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Endothelial cell. |
| [2] | "Human cyclooxygenase-2 cDNA." Hla T., Neilson K. Proc. Natl. Acad. Sci. U.S.A. 89:7384-7388(1992) [PubMed: 1380156] [Abstract] 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: 8181472] [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: 7945196] [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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [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. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [10] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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: 15489334] [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: 7947975] [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: 16373578] [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: 17113084] [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: 15308583] [Abstract] Cited for: VARIANT ALA-511. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | 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. | ||||||||||||
| IPI | IPI00018109. | ||||||||||||
| PIR | A46150. | ||||||||||||
| RefSeq | NP_000954.1. NM_000963.2. | ||||||||||||
| UniGene | Hs.196384. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
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| ProteinModelPortal | P35354. | ||||||||||||
| SMR | P35354. Positions 18-568. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP-28131N. | ||||||||||||
| STRING | P35354. | ||||||||||||
Protein family/group databases | |||||||||||||
| PeroxiBase | 3321. HsPGHS02. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | P35354. | ||||||||||||
Polymorphism databases | |||||||||||||
| DMDM | 3915797. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | P35354. | ||||||||||||
Protocols and materials databases | |||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000367468; ENSP00000356438; ENSG00000073756. | ||||||||||||
| GeneID | 5743. | ||||||||||||
| KEGG | hsa:5743. | ||||||||||||
| UCSC | uc001gsb.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 5743. | ||||||||||||
| GeneCards | GC01M186640. | ||||||||||||
| H-InvDB | HIX0001429. | ||||||||||||
| HGNC | HGNC:9605. PTGS2. | ||||||||||||
| HPA | CAB000113. HPA001335. | ||||||||||||
| MIM | 600262. gene. | ||||||||||||
| neXtProt | NX_P35354. | ||||||||||||
| PharmGKB | PA293. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | prNOG05919. | ||||||||||||
| HOGENOM | HBG402837. | ||||||||||||
| HOVERGEN | HBG000366. | ||||||||||||
| InParanoid | P35354. | ||||||||||||
| OMA | WEAFSNL. | ||||||||||||
| OrthoDB | EOG4H19VF. | ||||||||||||
| PhylomeDB | P35354. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BRENDA | 1.14.99.1. 2681. | ||||||||||||
| Pathway_Interaction_DB | nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes. tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway. s1p_s1p1_pathway. S1P1 pathway. p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta. | ||||||||||||
| Reactome | REACT_111217. Metabolism. REACT_22258. Metabolism of lipids and lipoproteins. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P35354. | ||||||||||||
| Bgee | P35354. | ||||||||||||
| CleanEx | HS_PTGS2. | ||||||||||||
| Genevestigator | P35354. | ||||||||||||
| GermOnline | ENSG00000073756. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR006210. EGF-like. IPR000742. EGF_3. IPR010255. Haem_peroxidase. IPR002007. Haem_peroxidase_animal. IPR019791. Haem_peroxidase_animal_subgr. [Graphical view] | ||||||||||||
| Gene3D | G3DSA:1.10.640.10. Haem_peroxidase_animal. 1 hit. | ||||||||||||
| KO | K11987. | ||||||||||||
| Pfam | PF03098. An_peroxidase. 1 hit. [Graphical view] | ||||||||||||
| PRINTS | PR00457. ANPEROXIDASE. | ||||||||||||
| SMART | SM00181. EGF. 1 hit. [Graphical view] | ||||||||||||
| SUPFAM | SSF48113. Peroxidase_super. 1 hit. | ||||||||||||
| PROSITE | PS00022. EGF_1. False negative. PS01186. EGF_2. False negative. PS50026. EGF_3. 1 hit. PS50292. PEROXIDASE_3. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other | |||||||||||||
| DrugBank | 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. | ||||||||||||
| NextBio | 22358. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | PGH2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P35354 Secondary accession number(s): A8K802, Q16876 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with