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Reviewed, UniProtKB/Swiss-Prot P35354 (PGH2_HUMAN)

Last modified June 16, 2009. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Prostaglandin G/H synthase 2
    EC=1.14.99.1
Alternative name(s):
    Cyclooxygenase-2
      Short name=COX-2
    Prostaglandin-endoperoxide synthase 2
    Prostaglandin H2 synthase 2
      Short name=PGH synthase 2
      Short name=PGHS-2
    PHS II
Gene names
Name: PTGS2
Synonyms: COX2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length604 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.

Catalytic activity

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

Cofactor

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

Pathway

Lipid metabolism; prostaglandin biosynthesis.

Subunit structure

Homodimer By similarity.

Subcellular location

Microsome membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein.

Induction

By cytokines and mitogens.

Involvement in disease

Likely to play a role in inflammatory diseases such as rheumatoid arthritis.

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.

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Lipid synthesis
Prostaglandin biosynthesis
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandHeme
Iron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
Peroxidase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Gene Ontology (GO)
   Biological processcell motion

Traceable author statement. Source: ProtInc

cyclooxygenase pathway

Non-traceable author statement. Source: UniProtKB

oxidation reduction

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of blood pressure

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of inflammatory response

Non-traceable author statement. Source: UniProtKB

response to oxidative stress

Inferred from electronic annotation. Source: InterPro

   Cellular componentendoplasmic reticulum lumen

Inferred from Experiment. Source: Reactome

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

microsome

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular functionheme binding

Inferred from electronic annotation. Source: InterPro

oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen

Inferred from electronic annotation. Source: UniProtKB-KW

peroxidase activity

Non-traceable author statement. Source: UniProtKB

prostaglandin-endoperoxide synthase activity

Non-traceable author statement. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 604587Prostaglandin G/H synthase 2
PRO_0000023875

Regions

Domain18 – 5538EGF-like

Sites

Active site1931Proton acceptor By similarity
Active site3711For cyclooxygenase activity By similarity
Metal binding3741Iron (heme axial ligand) By similarity
Site5161Aspirin-acetylated serine By similarity

Amino acid modifications

Modified residue4371Phosphoserine By similarity
Modified residue4461Phosphotyrosine By similarity
Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation1301N-linked (GlcNAc...) Potential
Glycosylation3961N-linked (GlcNAc...) Potential
Glycosylation5801N-linked (GlcNAc...) Potential
Disulfide bond21 ↔ 32 By similarity
Disulfide bond22 ↔ 145 By similarity
Disulfide bond26 ↔ 42 By similarity
Disulfide bond44 ↔ 54 By similarity
Disulfide bond555 ↔ 561 By similarity

Natural variations

Natural variant2281R → H: dbSNP rs3218622. Ref.6
VAR_016262
Natural variant4281P → A: dbSNP rs4648279. Ref.6
VAR_016263
Natural variant4881E → G: dbSNP rs5272.
VAR_011980
Natural variant5111V → A: dbSNP rs5273. Ref.6 Ref.11
VAR_011981
Natural variant5871G → R: dbSNP rs3218625. Ref.6
VAR_016264

Experimental info

Sequence conflict1651E → G in AAA58433. Ref.2
Sequence conflict4381I → T in AAA35803. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P35354-1 [UniParc].

Last modified December 15, 1998. Version 2.
Checksum: 72FBD699F6128519

FASTA60468,996
        10         20         30         40         50         60 
MLARALLLCA VLALSHTANP CCSHPCQNRG VCMSVGFDQY KCDCTRTGFY GENCSTPEFL 

        70         80         90        100        110        120 
TRIKLFLKPT PNTVHYILTH FKGFWNVVNN IPFLRNAIMS YVLTSRSHLI DSPPTYNADY 

       130        140        150        160        170        180 
GYKSWEAFSN LSYYTRALPP VPDDCPTPLG VKGKKQLPDS NEIVEKLLLR RKFIPDPQGS 

       190        200        210        220        230        240 
NMMFAFFAQH FTHQFFKTDH KRGPAFTNGL GHGVDLNHIY GETLARQRKL RLFKDGKMKY 

       250        260        270        280        290        300 
QIIDGEMYPP TVKDTQAEMI YPPQVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD 

       310        320        330        340        350        360 
VLKQEHPEWG DEQLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE LLFNKQFQYQ 

       370        380        390        400        410        420 
NRIAAEFNTL YHWHPLLPDT FQIHDQKYNY QQFIYNNSIL LEHGITQFVE SFTRQIAGRV 

       430        440        450        460        470        480 
AGGRNVPPAV QKVSQASIDQ SRQMKYQSFN EYRKRFMLKP YESFEELTGE KEMSAELEAL 

       490        500        510        520        530        540 
YGDIDAVELY PALLVEKPRP DAIFGETMVE VGAPFSLKGL MGNVICSPAY WKPSTFGGEV 

       550        560        570        580        590        600 
GFQIINTASI QSLICNNVKG CPFTSFSVPD PELIKTVTIN ASSSRSGLDD INPTVLLKER 


STEL 

« Hide

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]"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. expand/collapse author list , 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: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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.
[10]"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.
[11]"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

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.
AL033533 Genomic DNA. Translation: CAB41240.1.
BC013734 mRNA. Translation: AAH13734.1.
IPIIPI00018109.
PIRA46150.
RefSeqNP_000954.1.
UniGeneHs.196384

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1V0Xmodel-A1-604[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:28131N.

Protein family/group databases

PeroxiBase3321. HsPGHS02.

PTM databases

PhosphoSiteP35354.

Proteomic databases

PRIDEP35354.

Genome annotation databases

EnsemblENSG00000073756. Homo sapiens. [Contig view]
GeneID5743.
KEGGhsa:5743.

Organism-specific databases

GeneCardsGC01M184907.
H-InvDBHIX0001429.
HGNCHGNC:9605. PTGS2.
HPACAB000113.
HPA001335.
MIM600262. gene.
PharmGKBPA293.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP35354.
HOVERGENP35354.
OMAP35354. WEAFSNL.

Enzyme and pathway databases

BRENDA1.14.99.1. 247.
Pathway_Interaction_DBnfat_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.
ReactomeREACT_13433. Biological oxidations.
REACT_649. Phase 1 functionalization.

Gene expression databases

ArrayExpressP35354.
BgeeP35354.
CleanExHS_PTGS2.
GermOnlineENSG00000073756. Homo sapiens.

Family and domain databases

InterProIPR006209. EGF.
IPR006210. EGF-like.
IPR013032. EGF-like_reg_CS.
IPR000742. EGF_3.
IPR002007. Haem_peroxidase_animal.
IPR019791. Haem_peroxidase_animal_sg.
[Graphical view]
Gene3DG3DSA:1.10.640.10. Haem_peroxidase_animal. 1 hit.
PfamPF03098. An_peroxidase. 1 hit.
PF00008. EGF. 1 hit.
[Graphical view]
PRINTSPR00457. ANPEROXIDASE.
SMARTSM00181. EGF. 1 hit.
[Graphical view]
PROSITEPS00022. EGF_1. False negative.
PS01186. EGF_2. False negative.
PS50026. EGF_3. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00316. 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.
NextBio22358.
SOURCESearch...

Entry information

Entry namePGH2_HUMAN
AccessionPrimary (citable) accession number: P35354
Secondary accession number(s): Q16876
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: December 15, 1998
Last modified: June 16, 2009
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents