Reviewed, UniProtKB/Swiss-Prot P35354 (PGH2_HUMAN)

Names 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
    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

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	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 process	Fatty acid biosynthesis Lipid synthesis Prostaglandin biosynthesis
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Heme Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase Peroxidase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell 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 component	endoplasmic 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 function	heme 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 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
	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...) Potential
	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: dbSNP rs3218622. Ref.6		VAR_016262
	Natural variant	428	1	P → A: dbSNP rs4648279. Ref.6		VAR_016263
	Natural variant	488	1	E → G: dbSNP rs5272.		VAR_011980
	Natural variant	511	1	V → A: dbSNP rs5273. Ref.6 Ref.11		VAR_011981
	Natural variant	587	1	G → R: dbSNP rs3218625. Ref.6		VAR_016264
Experimental info
	Sequence conflict	165	1	E → G in AAA58433. Ref.2
	Sequence conflict	438	1	I → T in AAA35803. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P35354-1 [UniParc]. Last modified December 15, 1998. Version 2. Checksum: 72FBD699F6128519	FASTA	604	68,996
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00018109.

PIR

A46150.

RefSeq

NP_000954.1.

UniGene

Hs.196384

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1V0X	model	-	A	1-604	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:28131N.

Protein family/group databases

PeroxiBase

3321. HsPGHS02.

PTM databases

PhosphoSite

P35354.

Proteomic databases

PRIDE

P35354.

Genome annotation databases

Ensembl

ENSG00000073756. Homo sapiens. [Contig view]

GeneID

5743.

KEGG

hsa:5743.

Organism-specific databases

GeneCards

GC01M184907.

H-InvDB

HIX0001429.

HGNC

HGNC:9605. PTGS2.

HPA

CAB000113.
HPA001335.

MIM

600262. gene.

PharmGKB

PA293.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P35354.

HOVERGEN

P35354.

OMA

P35354. WEAFSNL.

Enzyme and pathway databases

BRENDA

1.14.99.1. 247.

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_13433. Biological oxidations.
REACT_649. Phase 1 functionalization.

Gene expression databases

ArrayExpress

P35354.

Bgee

P35354.

CleanEx

HS_PTGS2.

GermOnline

ENSG00000073756. Homo sapiens.

Family and domain databases

InterPro

IPR006209. EGF.
IPR006210. EGF-like.
IPR013032. EGF-like_reg_CS.
IPR000742. EGF_3.
IPR002007. Haem_peroxidase_animal.
IPR019791. Haem_peroxidase_animal_sg.
[Graphical view]

Gene3D

G3DSA:1.10.640.10. Haem_peroxidase_animal. 1 hit.

Pfam

PF03098. An_peroxidase. 1 hit.
PF00008. EGF. 1 hit.
[Graphical view]

PRINTS

PR00457. ANPEROXIDASE.

SMART

SM00181. EGF. 1 hit.
[Graphical view]

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 Resources

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): 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)