DegronMD - Q14164(IKBKE)

FUNCTION: Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1. {ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:19153231, ECO:0000269|PubMed:20188669, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:22532683, ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:23478265}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.Y671S	TCGA-73-4666	LUAD	TCGA	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation altering degron motif	0.712
p.Y671S	DO26230	LUAD	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation altering degron motif	0.712
p.P665T	TCGA-86-A4JF	LUAD	TCGA	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.25
p.P665T	DO45317	LUAD	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.25
p.P665S	TCGA-AP-A0LM	UCEC	TCGA	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.25
p.P665S	DO43306	UCEC	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.25
p.G689W	TCGA-D3-A3C8	SKCM	TCGA	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G689W	DO47636	SKCM	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.P672H	TCGA-EE-A20F	SKCM	TCGA	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation altering degron motif	0.6583
p.P672H	DO37961	SKCM	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation altering degron motif	0.6583
p.A661V	TCGA-EO-A22U	UCEC	TCGA	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1389
p.A661V	DO43755	UCEC	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1389
p.L681F	TCGA-ER-A19N	SKCM	TCGA	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation altering degron motif	0.587
p.L681F	DO37452	SKCM	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation altering degron motif	0.587
p.D678Y	DO229022	LICA	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation altering degron motif	0.6214
p.R676Q	DO222494	MELA	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation altering degron motif	0.6218
p.A661D	DO232761	PBCA	ICGC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1389
p.P665L	SIDM00958	Chronic Myelogenous Leukemia	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.25
p.P665L	ACH-000920	Leukemia	CCLE	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.25
p.G660E	SIDM00584	Osteosarcoma	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	SIDM00394	Cervical Carcinoma	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	SIDM01653	Non-Cancerous	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	SIDM00207	Glioblastoma	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	SIDM00018	Acute Myeloid Leukemia	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	SIDM01582	Gastric Carcinoma	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	SIDM01444	Glioblastoma	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	SIDM01343	Gastric Carcinoma	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	SIDM00015	Esophageal Squamous Cell Carcinoma	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	KO52	haematopoietic and lymphoid tissue	COSMIC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	SISO	cervix	COSMIC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.G660E	HuO-3N1	bone	COSMIC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1111
p.A663V	SIDM01259	B-Lymphoblastic Leukemia	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1944
p.A663V	ACH-001669	Leukemia	CCLE	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1944
p.A663V	ACH-002238	Leukemia	CCLE	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1944
p.A663V	GR-ST	haematopoietic and lymphoid tissue	COSMIC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1944
p.E688K	SIDM01001	Breast Carcinoma	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1389
p.E688K	ACH-000258	Breast Cancer	CCLE	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1389
p.E688K	DU-4475	breast	COSMIC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation rewiring degron network	0.1389
p.S664L	SIDM01511	Gastric Carcinoma	GDSC	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation blocking phosphorylation signal	0.6667
p.S664L	ACH-000746	Gastric Cancer	CCLE	IAPYPSPTRKDLLL	DEG_ODPH_VHL_1	668:681	Mutation blocking phosphorylation signal	0.6667

Kaplan plot for IKBKE in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

IKBKE

UniProt ID: Q14164

Entrez ID: 9641

Protein name: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IKBKE in