DegronMD - Q9Y572(RIPK3)

FUNCTION: Serine/threonine-protein kinase that activates necroptosis and apoptosis, two parallel forms of cell death (PubMed:19524512, PubMed:19524513, PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:29883609, PubMed:32657447). Necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, is triggered by RIPK3 following activation by ZBP1 (PubMed:19524512, PubMed:19524513, PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:29883609, PubMed:32298652). Activated RIPK3 forms a necrosis-inducing complex and mediates phosphorylation of MLKL, promoting MLKL localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage (PubMed:19524512, PubMed:19524513, PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:25316792, PubMed:29883609). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (By similarity). Also regulates apoptosis: apoptosis depends on RIPK1, FADD and CASP8, and is independent of MLKL and RIPK3 kinase activity (By similarity). Phosphorylates RIPK1: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:19524513). In some cell types, also able to restrict viral replication by promoting cell death-independent responses (By similarity). In response to Zika virus infection in neurons, promotes a cell death-independent pathway that restricts viral replication: together with ZBP1, promotes a death-independent transcriptional program that modifies the cellular metabolism via up-regulation expression of the enzyme ACOD1/IRG1 and production of the metabolite itaconate (By similarity). Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (By similarity). RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL (PubMed:19498109). These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production (PubMed:19498109). {ECO:0000250|UniProtKB:Q9QZL0, ECO:0000269|PubMed:19498109, ECO:0000269|PubMed:19524512, ECO:0000269|PubMed:19524513, ECO:0000269|PubMed:22265413, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:22421439, ECO:0000269|PubMed:25316792, ECO:0000269|PubMed:29883609, ECO:0000269|PubMed:32298652, ECO:0000269|PubMed:32657447}.; FUNCTION: (Microbial infection) In case of herpes simplex virus 1/HHV-1 infection, forms heteromeric amyloid structures with HHV-1 protein RIR1/ICP6 which may inhibit RIPK3-mediated necroptosis, thereby preventing host cell death pathway and allowing viral evasion. {ECO:0000269|PubMed:33348174}. View more >>

GO - Biological processes (BP): 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.W266C	TCGA-66-2771	LUSC	TCGA	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation rewiring degron network	0.0556
p.W266C	DO26870	LUSC	ICGC	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation rewiring degron network	0.0556
p.S391L	TCGA-AA-A00N	COAD	TCGA	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.2222
p.S391L	TCGA-AA-A00N	COAD	TCGA	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.2778
p.S391L	TCGA-AA-A00N	COAD	TCGA	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1111
p.S391L	DO9876	COAD	ICGC	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.2222
p.S391L	DO9876	COAD	ICGC	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.2778
p.S391L	DO9876	COAD	ICGC	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1111
p.S391L	SIDM01276	Colorectal Carcinoma	GDSC	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.2222
p.S391L	SIDM01276	Colorectal Carcinoma	GDSC	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.2778
p.S391L	SIDM01276	Colorectal Carcinoma	GDSC	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1111
p.R239W	TCGA-AX-A3FT	UCEC	TCGA	NRPSLAELP	DEG_APCC_DBOX_1	238:246	Mutation altering degron motif	0.8634
p.R239W	DO40801	UCEC	ICGC	NRPSLAELP	DEG_APCC_DBOX_1	238:246	Mutation altering degron motif	0.8634
p.Q375R	TCGA-CG-5723	STAD	TCGA	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.0556
p.Q375R	DO38376	STAD	ICGC	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.0556
p.P409S	TCGA-CK-4951	COAD	TCGA	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.1389
p.P409S	TCGA-CK-4951	COAD	TCGA	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1667
p.P409S	DO10582	COAD	ICGC	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.1389
p.P409S	DO10582	COAD	ICGC	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1667
p.P409H	TCGA-D3-A2J6	SKCM	TCGA	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.1389
p.P409H	TCGA-D3-A2J6	SKCM	TCGA	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1667
p.P409H	DO37901	SKCM	ICGC	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.1389
p.P409H	DO37901	SKCM	ICGC	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1667
p.Q237K	TCGA-D8-A1XK	BRCA	TCGA	NRPSLAELP	DEG_APCC_DBOX_1	238:246	Mutation rewiring degron network	0.3056
p.Q237K	DO4749	BRCA	ICGC	NRPSLAELP	DEG_APCC_DBOX_1	238:246	Mutation rewiring degron network	0.3056
p.E376K	TCGA-DA-A1I7	SKCM	TCGA	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.0833
p.E376K	DO37951	SKCM	ICGC	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.0833
p.P411S	TCGA-EE-A29L	SKCM	TCGA	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.0833
p.P411S	TCGA-EE-A29L	SKCM	TCGA	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1111
p.P411S	DO222599	MELA	ICGC	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.0833
p.P411S	DO222599	MELA	ICGC	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1111
p.P411S	DO37835	SKCM	ICGC	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.0833
p.P411S	DO37835	SKCM	ICGC	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1111
p.E251D	TCGA-EO-A3B0	UCEC	TCGA	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation altering degron motif	0.5647
p.E251D	DO219773	UCEC	ICGC	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation altering degron motif	0.5647
p.E231K	TCGA-F5-6814	READ	TCGA	NRPSLAELP	DEG_APCC_DBOX_1	238:246	Mutation rewiring degron network	0.1389
p.E231K	DO36556	READ	ICGC	NRPSLAELP	DEG_APCC_DBOX_1	238:246	Mutation rewiring degron network	0.1389
p.D390Y	TCGA-FI-A2D0	UCEC	TCGA	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.1944
p.D390Y	TCGA-FI-A2D0	UCEC	TCGA	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.3056
p.D390Y	TCGA-FI-A2D0	UCEC	TCGA	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.0833
p.D390Y	DO43891	UCEC	ICGC	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.1944
p.D390Y	DO43891	UCEC	ICGC	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.3056
p.D390Y	DO43891	UCEC	ICGC	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.0833
p.W266L	TCGA-FS-A1ZG	SKCM	TCGA	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation rewiring degron network	0.0556
p.W266L	DO37523	SKCM	ICGC	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation rewiring degron network	0.0556
p.P380S	TCGA-GN-A8LK	SKCM	TCGA	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.1944
p.P380S	DO51259	SKCM	ICGC	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.1944
p.E251Q	TCGA-K4-A6MB	BLCA	TCGA	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation altering degron motif	0.5633
p.E251Q	DO44077	BLCA	ICGC	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation altering degron motif	0.5633
p.T384A	DO48420	BLCA	ICGC	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.3056
p.A393D	DO228952	LICA	ICGC	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation rewiring degron network	0.2778
p.A393D	DO228952	LICA	ICGC	AGTSS	DEG_SPOP_SBC_1	385:389	Mutation rewiring degron network	0.2222
p.A393D	DO228952	LICA	ICGC	PETST	DEG_SPOP_SBC_1	399:403	Mutation rewiring degron network	0.1667
p.S410R	DO229036	LICA	ICGC	PPQTPETS	DEG_SCF_FBW7_1	395:402	Mutation blocking phosphorylation signal	0.5556
p.S410R	DO229036	LICA	ICGC	PETST	DEG_SPOP_SBC_1	399:403	Mutation blocking phosphorylation signal	0.5833
p.L261I	DO229045	LICA	ICGC	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation rewiring degron network	0.1944
p.R239Q	SIDM02049	Pancreatic Carcinoma	GDSC	NRPSLAELP	DEG_APCC_DBOX_1	238:246	Mutation altering degron motif	0.7329
p.R239Q	SIDM00454	Rhabdomyosarcoma	GDSC	NRPSLAELP	DEG_APCC_DBOX_1	238:246	Mutation altering degron motif	0.7329
p.G254S	SIDM00251	Gastric Carcinoma	GDSC	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation altering degron motif	0.5882
p.G254S	ACH-000949	Gastric Cancer	CCLE	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation altering degron motif	0.5882
p.G254S	TGBC11TKB	stomach	COSMIC	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation altering degron motif	0.5882
p.T403A	SIDM01711	Non-Cancerous	GDSC	PETST	DEG_SPOP_SBC_1	399:403	Mutation altering degron motif	0.7139
p.T403A	ACH-002350	Non-Cancerous	CCLE	PETST	DEG_SPOP_SBC_1	399:403	Mutation altering degron motif	0.7139
p.T403P	SIDM00368	Small Cell Lung Carcinoma	GDSC	PETST	DEG_SPOP_SBC_1	399:403	Mutation altering degron motif	0.7031
p.E260V	SIDM00956	Esophageal Squamous Cell Carcinoma	GDSC	PETPGLE	DEG_SCF_FBW7_2	250:256	Mutation rewiring degron network	0.2222

Kaplan plot for RIPK3 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

RIPK3

UniProt ID: Q9Y572

Entrez ID: 11035

Protein name: Receptor-interacting serine/threonine-protein kinase 3 (EC 2.7.11.1) (RIP-like protein kinase 3) (Receptor-interacting protein 3) (RIP-3)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for RIPK3 in