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FLASH GENE

Symbol

PTGS2

contributors: mct - updated : 25-12-2016

HGNC name	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)
HGNC id	9605

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	1q31.1      Physical location : 186.640.944 - 186.649.559
Synonym name	cyclooxygenase 2
	prostaglandin G/H synthase and cyclooxygenase
	PGH synthase 2
	PHS II
Synonym symbol(s)	COX2, PGH2, PGHS2, COX-2, GRIPGHS, PGG/HS
EC.number	1.14.99.1

DNA

TYPE	functioning gene
STRUCTURE	8.61 kb     10 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor   HRE
motif	repetitive sequence   other
text structure	5'-flanking region has shown several potential transcription regulatory sequences, including a TATA box, a C/EBP motif, two AP-2 sites, three SP1 sites, two NF-kappa B sites, a CRE motif and an Ets-1 site (Appleby 1994)
	three SNP in the promoter
	regulation of the promoter by an interplay between two opposite beta isoforms of CCAAT/enhancer binding protein and p300 coactivator
	a Lef1-binding site at the 3 prime region of the genomic locus
	promoter activity was repressed upon SNAI1 overexpression

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000963 10 - 4507 NP_000954 - 604 - PMID: 7945196

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly   pharynx       highly Reproductive female system uterus cervix   highly   male system prostate     highly   male system seminal vesicles         male system male genital tract ejaculatory duct

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, growth/childhood, puberty

Text	seminal vesicles and ejaculatory ducts,prebubertal period

PROTEIN

PHYSICAL PROPERTIES		Hydrophobic
STRUCTURE

motifs/domains	a single eight-stranded continuously hydrogen-bunded antiparallel beta-barrel which encloses an internal ligand binding site
	one EGF-like domain

mono polymer

homomer , dimer

HOMOLOGY

interspecies

homolog to murine Ptgs2

Homologene

FAMILY	Kernel group, lipocalin family
	prostaglandin G/H synthase family

CATEGORY

enzyme , protooncogene , transport

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic,microsome

basic FUNCTION	prostaglandin G/H synthase, potent mediator of inflammation and role for prostanoid signaling in activity dependent plasticity
	oxidoreductase/electron transporter
	inducible enzyme that plays an important role in several pathophysiological processes, including inflammation, angiogenesis, and tumorigenesis( may be involved in the regulation of angiogenesis in pituitary tumors)
	playing an important role in ischemic proliferative retinopathy, as in diabetes
	stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, EP2
	catalyzing the crucial step of the production of prostaglandin E2, which is a principal mediator of joint inflammation such as rheumatoid arthritis and osteoarthritis
	may also play a role in pterygium formation
	is transcriptionally active before and after labour
	in cardiomyocytes, influences cardiac rhythm and function
	with ST6GALNAC5 and HBEGF, are mediators of cancer cell passage through the blood-brain barrier
	PTGES and PTGS2 are co-localized and act together to exacerbate stroke injury, by excessive PGE(2) production
	plays an important role in GDF2 induced osteogenic differentiation in mesenchymal stem cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

electron transport

PATHWAY

metabolism

signaling

role of the CPSF4/PTGS2 signaling pathway in the regulation of lung cancer growth and progression

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with ADIPOQ and PRKAB1 to protects the heart from ischemia-reperfusion injury
	interacting with ELAVL1(can stabilize the mRNA of PTGS2, and cytoplasmic expression of ELAVL1 is associated with increased PTGS2 expression in some cancers)
	negatively regulating STK17B, a serine-threonine kinase implicated in the regulation of apoptosis, suggesting a novel mechanism for the effect of PTGS2 on cancer cell survival
	PTGS2 and GDF2 may form an important regulatory loop to orchestrate the osteogenic differentiation in mesenchymal stem cells
	PTGS2 and and VEGFC are inducers of lymphangiogenesis and their expression levels were correlated in non-Hodgkin lymphoma
	apoptosis-enhancing effect of FAU-BCL2L14 is due in part to down-regulation of PTGS2 activation in macrophages
	MAT2A interacts with histone methyltransferase SETDB1 and inhibits PTGS2 gene expression
	RXRA suppresses PGE2 production through inhibiting NFKB activity and PTGS2 expression
	CAV1 may be a cofactor in the interaction of DERL1 and PTGS2 and may facilitate DERL1- and VCP complex-mediated PTGS2 ubiquitination, retrotranslocation, and degradation
	AREG, BTC, and EREG induced prostaglandin E2 (PGE2) production by upregulating PTGS2 expression through ERK1/2 signaling in granulosa cells
	role for ADRB1 in the downregulation of PTGS2
	PTH can stimulate a novel negative feedback of its anabolic actions by stimulating TNFSF1l and PTGS2 expression
	CPSF4 bind to PTGS2 promoter sequences directly and activate the transcription of PTGS2

cell & other

REGULATION

activated by

inducible nitric oxide synthase (NOS2A)

induced by

mitogen and cytokine inducible form

Other	regulated by an endogenous cellular factor
	regulated by LEF1 with CTNN1B in arthritic chondrocytes

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in squamous cell carcinoma of the head and neck, in retinoblastoma, and in cholangiocarcinoma tumoral     --over   in lung and colon adenocarcinoma, pituitary tumors and mammary tumors, in colorectal adenomas tumoral     --over   correlated with K-RAS mutation in colorectal adenoma in progression constitutional     --over   in neurals cell of the myenteric plexus in active inflammatory bowel disease constitutional     --over   in amyotrophic lateral sclerosis tumoral     --over   in renal call carcinoma constitutional       loss of function in cardiomyocytes may contribute to heart failure in patients receiving nonsteroidal anti-inflammatory drugs specific for inhibition of PTGS2 tumoral     --over   in colorectal cancer (CRC), rendering tumour cells resistant to apoptosis constitutional     --over   in the amnion is critical for the production of prostaglandins that induce labour tumoral     --low   in squamous cell carcinoma (SCC) (pMID: 23261444) tumoral     --over   of CPSF4 and PTGS2 proteins predicted poor prognosis of patients with lung cancers

Susceptibility

to type 2 diabetes mellitus in Pima indians to development of prostate cancer to aspirin resistance

Variant & Polymorphism SNP , insertion/deletion	allele C associated with decreased promoter activity and susceptibility to type 2 diabetes mellitus
	SNP -297G was associated with a decreased risk for prostate cancer
	partial deletion of exon 5 associated with aspirin resistance

Candidate gene	for treatment of amyotrophic lateral sclerosis
Marker
Therapy target

ANIMAL & CELL MODELS