P35355 (PGH2_RAT) Reviewed, UniProtKB/Swiss-Prot

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
PHS II
Prostaglandin H2 synthase 2
Short name=PGH synthase 2
Short name=PGHS-2
Prostaglandin-endoperoxide synthase 2

Gene names

Name:	Ptgs2
Synonyms:	Cox-2, Cox2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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 By similarity.
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.
Tissue specificity	Expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus.
Induction	By cytokines and mitogens.
Post-translational modification	S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-561 By similarity.
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 Fatty acid metabolism Lipid biosynthesis Lipid metabolism Prostaglandin biosynthesis Prostaglandin metabolism
Cellular component	Endoplasmic reticulum Membrane Microsome
Domain	Signal
Ligand	Heme Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase Peroxidase
PTM	Disulfide bond Glycoprotein Phosphoprotein S-nitrosylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	anagen Inferred from electronic annotation. Source: Compara angiogenesis Inferred from mutant phenotype PubMed 21273371. Source: RGD bone mineralization Inferred from mutant phenotype PubMed 18519738. Source: MGI brown fat cell differentiation Inferred from electronic annotation. Source: Compara cellular response to ATP Inferred from expression pattern PubMed 21678415. Source: RGD cellular response to UV Inferred from expression pattern PubMed 22306367. Source: RGD cellular response to hypoxia Inferred from electronic annotation. Source: Compara cellular response to mechanical stimulus Inferred from expression pattern PubMed 21051526. Source: RGD cyclooxygenase pathway Inferred from sequence or structural similarity. Source: UniProtKB decidualization Inferred from mutant phenotype PubMed 17485303. Source: RGD embryo implantation Inferred from mutant phenotype PubMed 17485303. Source: RGD hair cycle Inferred from expression pattern PubMed 19180200. Source: RGD inflammatory response Inferred from mutant phenotype PubMed 17701021. Source: RGD learning Inferred from mutant phenotype PubMed 21701788. Source: RGD maintenance of blood-brain barrier Inferred from mutant phenotype PubMed 17704356. Source: RGD memory Inferred from mutant phenotype PubMed 18540883. Source: RGD negative regulation of calcium ion transport Inferred from mutant phenotype PubMed 17766482. Source: RGD negative regulation of cell cycle Inferred from genetic interaction PubMed 11756433. Source: RGD negative regulation of cell proliferation Inferred from direct assay PubMed 11756433. Source: RGD negative regulation of smooth muscle contraction Inferred from mutant phenotype PubMed 21051526. Source: RGD negative regulation of synaptic transmission, dopaminergic Inferred from mutant phenotype PubMed 18764909. Source: RGD ovulation Inferred from mutant phenotype PubMed 17485303. Source: RGD positive regulation of NF-kappaB import into nucleus Inferred from mutant phenotype PubMed 20472710. Source: RGD positive regulation of apoptotic process Inferred from mutant phenotype PubMed 17828456. Source: RGD positive regulation of brown fat cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of cell migration involved in sprouting angiogenesis Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL positive regulation of fever generation Inferred from direct assay PubMed 19940926. Source: BHF-UCL positive regulation of fibroblast growth factor production Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL positive regulation of nitric oxide biosynthetic process Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL positive regulation of platelet-derived growth factor production Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL positive regulation of smooth muscle cell proliferation Inferred from mutant phenotype PubMed 17645304. Source: RGD positive regulation of smooth muscle contraction Inferred from mutant phenotype PubMed 18480553. Source: RGD positive regulation of synaptic plasticity Inferred from mutant phenotype PubMed 18540883. Source: RGD positive regulation of synaptic transmission, glutamatergic Inferred from mutant phenotype PubMed 18764909. Source: RGD positive regulation of transforming growth factor beta production Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL positive regulation of vasoconstriction Inferred from mutant phenotype PubMed 18456673. Source: RGD positive regulation vascular endothelial growth factor production Inferred from mutant phenotype PubMed 9630216. Source: BHF-UCL regulation of blood pressure Inferred from sequence or structural similarity. Source: UniProtKB response to drug Inferred from expression pattern PubMed 17883899. Source: RGD response to estradiol stimulus Inferred from expression pattern PubMed 18310519. Source: RGD response to fatty acid Inferred from expression pattern PubMed 16983392. Source: RGD response to fructose stimulus Inferred from expression pattern PubMed 17883899. Source: RGD response to glucocorticoid stimulus Inferred from expression pattern PubMed 18657281. Source: RGD response to lipopolysaccharide Inferred from mutant phenotype PubMed 17766482. Source: RGD response to lithium ion Inferred from expression pattern PubMed 12232777. Source: RGD response to manganese ion Inferred from expression pattern PubMed 17827730. Source: RGD response to oxidative stress Inferred from electronic annotation. Source: InterPro response to tumor necrosis factor Inferred from expression pattern PubMed 17704356. Source: RGD response to vitamin D Inferred from expression pattern PubMed 18348265. Source: RGD sensory perception of pain Inferred from mutant phenotype PubMed 21362433. Source: RGD
Cellular_component	endoplasmic reticulum Traceable author statement PubMed 11756433. Source: RGD endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell neuron projection Inferred from electronic annotation. Source: Compara nuclear envelope Traceable author statement PubMed 11756433. Source: RGD protein complex Inferred from direct assay PubMed 16479074. Source: RGD
Molecular_function	heme binding Inferred from sequence or structural similarity. Source: UniProtKB lipid binding Inferred from mutant phenotype PubMed 17245358. Source: RGD metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from direct assay Ref.3. Source: RGD peroxidase activity Inferred from electronic annotation. Source: UniProtKB-KW prostaglandin-endoperoxide synthase activity Inferred from sequence or structural similarity. 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	Ref.6
	Chain	18 – 604	587	Prostaglandin G/H synthase 2		PRO_0000023879
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
	Binding site	106	1	Substrate By similarity
	Binding site	341	1	Substrate By similarity
	Binding site	371	1	Substrate 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 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
Experimental info
	Sequence conflict	11 – 13	3	ALA → CPG Ref.4
	Sequence conflict	11 – 13	3	ALA → CPG Ref.5
	Sequence conflict	58	1	E → R Ref.4
	Sequence conflict	58	1	E → R Ref.5
	Sequence conflict	66	1	L → P Ref.4
	Sequence conflict	66	1	L → P Ref.5
	Sequence conflict	96 – 98	3	NSI → IQS Ref.4
	Sequence conflict	96 – 98	3	NSI → IQS Ref.5
	Sequence conflict	339	1	S → R Ref.4
	Sequence conflict	339	1	S → R Ref.5
	Sequence conflict	344	1	K → Q Ref.4
	Sequence conflict	344	1	K → Q Ref.5
	Sequence conflict	350	1	E → D Ref.4
	Sequence conflict	350	1	E → D Ref.5
	Sequence conflict	368	1	N → K Ref.4
	Sequence conflict	368	1	N → K Ref.5
	Sequence conflict	573	1	P → A Ref.4
	Sequence conflict	573	1	P → A Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P35355 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 98E418825D98FF0C	FASTA	604	69,164
	10 20 30 40 50 60 MLFRAVLLCA ALALSHAANP CCSNPCQNRG ECMSIGFDQY KCDCTRTGFY GENCTTPEFL 70 80 90 100 110 120 TRIKLLLKPT PNTVHYILTH FKGVWNIVNN IPFLRNSIMR YVLTSRSHLI DSPPTYNVHY 130 140 150 160 170 180 GYKSWEAFSN LSYYTRALPP VADDCPTPMG VKGNKELPDS KEVLEKVLLR REFIPDPQGT 190 200 210 220 230 240 NMMFAFFAQH FTHQFFKTDQ KRGPGFTRGL GHGVDLNHVY GETLDRQHKL RLFQDGKLKY 250 260 270 280 290 300 QVIGGEVYPP TVKDTQVDMI YPPHVPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD 310 320 330 340 350 360 ILKQEHPEWD DERLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE LLFNQQFQYQ 370 380 390 400 410 420 NRIASEFNTL YHWHPLLPDT FNIEDQEYTF KQFLYNNSIL LEHGLAHFVE SFTRQIAGRV 430 440 450 460 470 480 AGGRNVPIAV QAVAKASIDQ SREMKYQSLN EYRKRFSLKP YTSFEELTGE KEMAAELKAL 490 500 510 520 530 540 YHDIDAMELY PALLVEKPRP DAIFGETMVE LGAPFSLKGL MGNPICSPQY WKPSTFGGEV 550 560 570 580 590 600 GFRIINTASI QSLICNNVKG CPFASFNVQD PQPTKTATIN ASASHSRLDD INPTVLIKRR STEL

References

[1]	"Cloning and expression of rat prostaglandin endoperoxide synthase (cyclooxygenase)-2 cDNA." Kennedy B.P., Chan C.C., Culp S.A., Cromlish W.A. Biochem. Biophys. Res. Commun. 197:494-500(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids." Yamagata K., Andreasson K.I., Kaufmann W.E., Barnes C.A., Worley P.F. Neuron 11:371-386(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning and characterization of a growth factor-inducible cyclooxygenase gene from rat intestinal epithelial cells." Dubois R.N., Tsujii M., Bishop P., Awad J.A., Makita K., Lanahan A. Am. J. Physiol. 266:G822-G827(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Intestine.
[4]	"Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression." Feng L., Sun W., Xia Y., Tang W.W., Chanmugam P., Soyoola E., Wilson C.B., Hwang D. Arch. Biochem. Biophys. 307:361-368(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Fischer 344.
[5]	"Immediate-early MEK-1-dependent stabilization of rat smooth muscle cell cyclooxygenase-2 mRNA by Galpha(q)-coupled receptor signaling." Xu K., Robida A.M., Murphy T.J. J. Biol. Chem. 275:23012-23019(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Purification and characterization of a novel, distinct isoform of prostaglandin endoperoxide synthase induced by human chorionic gonadotropin in granulosa cells of rat preovulatory follicles." Sirois J., Richards J.S. J. Biol. Chem. 267:6382-6388(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-43.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L25925 mRNA. Translation: AAA16477.1. U04300 mRNA. Translation: AAA20246.1. U03389 mRNA. Translation: AAA03466.1. S67722 mRNA. Translation: AAB29401.1. AF233596 mRNA. Translation: AAF36986.1.
IPI	IPI00197645.
PIR	JC2030.
RefSeq	NP_058928.3. NM_017232.3.
UniGene	Rn.44369.
3D structure databases
ProteinModelPortal	P35355.
SMR	P35355. Positions 18-569.
ModBase	Search...
Protein family/group databases
PeroxiBase	3975. RnoPGHS02-A.
PTM databases
PhosphoSite	P35355.
Proteomic databases
PaxDb	P35355.
PRIDE	P35355.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000003567; ENSRNOP00000003567; ENSRNOG00000002525.
GeneID	29527.
KEGG	rno:29527.
UCSC	RGD:620349. rat.
Organism-specific databases
CTD	5743.
RGD	620349. Ptgs2.
Phylogenomic databases
eggNOG	NOG39991.
GeneTree	ENSGT00390000010743.
HOGENOM	HOG000013149.
HOVERGEN	HBG000366.
InParanoid	P35355.
KO	K11987.
OMA	THFKGVW.
OrthoDB	EOG4H19VF.
Enzyme and pathway databases
UniPathway	UPA00662.
Gene expression databases
Genevestigator	P35355.
GermOnline	ENSRNOG00000002525. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.640.10. 1 hit.
InterPro	IPR000742. EG-like_dom. IPR010255. Haem_peroxidase. IPR002007. Haem_peroxidase_animal. IPR019791. Haem_peroxidase_animal_subgr. [Graphical view]
Pfam	PF03098. An_peroxidase. 2 hits. [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
BindingDB	P35355.
ChEMBL	CHEMBL2977.
NextBio	609492.

Entry information

Entry name

PGH2_RAT

Accession

Primary (citable) accession number: P35355
Secondary accession number(s): Q64379, Q925V4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	April 3, 2013
This is version 130 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program