DegronMD - P35354(PTGS2)

FUNCTION: Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate, with a particular role in the inflammatory response (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:11939906, PubMed:19540099). The cyclooxygenase activity oxygenates arachidonate (AA, C20:4(n-6)) to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide PGH2, the precursor of all 2-series prostaglandins and thromboxanes (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity). {ECO:0000250|UniProtKB:Q05769, ECO:0000269|PubMed:11034610, ECO:0000269|PubMed:11192938, ECO:0000269|PubMed:11939906, ECO:0000269|PubMed:12391014, ECO:0000269|PubMed:16373578, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:22068350, ECO:0000269|PubMed:22942274, ECO:0000269|PubMed:26236990, ECO:0000269|PubMed:26282205, ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27642067, ECO:0000269|PubMed:7592599, ECO:0000269|PubMed:7947975, ECO:0000269|PubMed:9048568, ECO:0000269|PubMed:9261177, ECO:0000303|PubMed:19540099}. View more >>

GO - Biological processes (BP): aging [GO:0007568]; angiogenesis [GO:0001525]; bone mineralization [GO:0030282]; brown fat cell differentiation [GO:0050873]; cellular response to ATP [GO:0071318]; cellular response to fluid shear stress [GO:0071498]; cellular response to heat [GO:0034605]; cellular response to hypoxia [GO:0071456]; cellular response to lead ion [GO:0071284]; cellular response to mechanical stimulus [GO:0071260]; cellular response to non-ionic osmotic stress [GO:0071471]; cellular response to UV [GO:0034644]; cyclooxygenase pathway [GO:0019371]; decidualization [GO:0046697]; embryo implantation [GO:0007566]; hair cycle [GO:0042633]; inflammatory response [GO:0006954]; learning [GO:0007612]; maintenance of blood-brain barrier [GO:0035633]; memory [GO:0007613]; negative regulation of calcium ion transport [GO:0051926]; negative regulation of cell cycle [GO:0045786]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043154]; negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress [GO:1902219]; negative regulation of smooth muscle contraction [GO:0045986]; negative regulation of synaptic transmission, dopaminergic [GO:0032227]; ovulation [GO:0030728]; positive regulation of apoptotic process [GO:0043065]; positive regulation of brown fat cell differentiation [GO:0090336]; positive regulation of cell migration involved in sprouting angiogenesis [GO:0090050]; positive regulation of fever generation [GO:0031622]; positive regulation of fibroblast growth factor production [GO:0090271]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of platelet-derived growth factor production [GO:0090362]; positive regulation of prostaglandin biosynthetic process [GO:0031394]; positive regulation of protein import into nucleus [GO:0042307]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of smooth muscle contraction [GO:0045987]; positive regulation of synaptic plasticity [GO:0031915]; positive regulation of synaptic transmission, glutamatergic [GO:0051968]; positive regulation of transforming growth factor beta production [GO:0071636]; positive regulation of vascular endothelial growth factor production [GO:0010575]; positive regulation of vasoconstriction [GO:0045907]; prostaglandin biosynthetic process [GO:0001516]; regulation of blood pressure [GO:0008217]; regulation of inflammatory response [GO:0050727]; regulation of neuroinflammatory response [GO:0150077]; response to angiotensin [GO:1990776]; response to estradiol [GO:0032355]; response to fatty acid [GO:0070542]; response to fructose [GO:0009750]; response to glucocorticoid [GO:0051384]; response to lipopolysaccharide [GO:0032496]; response to lithium ion [GO:0010226]; response to manganese ion [GO:0010042]; response to oxidative stress [GO:0006979]; response to tumor necrosis factor [GO:0034612]; response to vitamin D [GO:0033280]; response to xenobiotic stimulus [GO:0009410]; sensory perception of pain [GO:0019233] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.L232I	TCGA-44-7662	LUAD	TCGA	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.6063
p.L232I	DO23597	LUAD	ICGC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.6063
p.R231H	TCGA-AP-A0LM	UCEC	TCGA	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.7133
p.R231H	TCGA-CA-6717	COAD	TCGA	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.7133
p.R231H	DO8264	COAD	ICGC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.7133
p.R231H	DO43306	UCEC	ICGC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.7133
p.R228H	TCGA-BH-A0DD	BRCA	TCGA	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228H	TCGA-P6-A5OG	ACC	TCGA	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228H	DO2008	BRCA	ICGC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228H	SIDM00435	Acute Myeloid Leukemia	GDSC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228H	SIDM00618	Hepatocellular Carcinoma	GDSC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228H	SIDM00361	Non-Small Cell Lung Carcinoma	GDSC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228H	SIDM01694	B-Lymphoblastic Leukemia	GDSC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R231C	TCGA-E9-A1QZ	BRCA	TCGA	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.719
p.R231C	DO4737	BRCA	ICGC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.719
p.R231C	DO33344	PACA	ICGC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.719
p.R231C	SIDM00214	Colorectal Carcinoma	GDSC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.719
p.R231C	ACH-000955	Colon/Colorectal Cancer	CCLE	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.719
p.R231C	SNU-407	large intestine	COSMIC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation altering degron motif	0.719
p.R228C	TCGA-XK-AAIW	PRAD	TCGA	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228C	DO51407	PRAD	ICGC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228C	SIDM00217	Colorectal Carcinoma	GDSC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228C	ACH-000999	Colon/Colorectal Cancer	CCLE	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228C	SNU-1040	large intestine	COSMIC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.R228S	DO231965	LICA	ICGC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.2778
p.Q227K	DO229018	LICA	ICGC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.25
p.Y240C	SIDM01113	Other Sarcomas	GDSC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.1944
p.Y240C	ACH-000939	Sarcoma	CCLE	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.1944
p.Y240C	SK-UT-1	soft tissue	COSMIC	LRLFKD	LIG_APCC_ABBA_1	230:235	Mutation rewiring degron network	0.1944

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PTGS2

UniProt ID: P35354

Entrez ID: 5743

Protein name: Prostaglandin G/H synthase 2 (EC 1.14.99.1) (Cyclooxygenase-2) (COX-2) (PHS II) (Prostaglandin H2 synthase 2) (PGH synthase 2) (PGHS-2) (Prostaglandin-endoperoxide synthase 2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PTGS2 in