DegronMD - P08887(IL6R)

FUNCTION: Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis (PubMed:30995492, PubMed:31235509). The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable). {ECO:0000269|PubMed:28265003, ECO:0000269|PubMed:31235509, ECO:0000305|PubMed:30995492}.; FUNCTION: [Isoform 1]: Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells (By similarity). {ECO:0000250|UniProtKB:P22272, ECO:0000305|PubMed:30995492}.; FUNCTION: [Isoform 2]: Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364). In complex with IL6, is required for induction of VEGF production (PubMed:12794819). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity). {ECO:0000250|UniProtKB:P22272, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:21990364}.; FUNCTION: [Soluble interleukin-6 receptor subunit alpha]: Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364). In complex with IL6, is required for induction of VEGF production (PubMed:12794819). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity). {ECO:0000250|UniProtKB:P22272, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:21990364}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R137L	TCGA-05-4396	LUAD	TCGA	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.7316
p.R137L	DO23838	LUAD	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.7316
p.A323S	TCGA-12-1093	GBM	TCGA	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation rewiring degron network	0.1667
p.A323S	DO14097	GBM	ICGC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation rewiring degron network	0.1667
p.A323S	DO229026	LICA	ICGC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation rewiring degron network	0.1667
p.T105S	TCGA-50-5932	LUAD	TCGA	DSGNYS	DEG_SCF_TRCP1_1	90:95	Mutation rewiring degron network	0.0556
p.T105S	DO23610	LUAD	ICGC	DSGNYS	DEG_SCF_TRCP1_1	90:95	Mutation rewiring degron network	0.0556
p.E324Q	TCGA-64-1677	LUAD	TCGA	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation rewiring degron network	0.1389
p.E324Q	DO23996	LUAD	ICGC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation rewiring degron network	0.1389
p.V147M	TCGA-A5-A0G2	UCEC	TCGA	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation rewiring degron network	0.2222
p.V147M	DO41235	UCEC	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation rewiring degron network	0.2222
p.R80G	TCGA-BS-A0UF	UCEC	TCGA	DSGNYS	DEG_SCF_TRCP1_1	90:95	Mutation rewiring degron network	0.0556
p.R80G	DO41488	UCEC	ICGC	DSGNYS	DEG_SCF_TRCP1_1	90:95	Mutation rewiring degron network	0.0556
p.P136L	TCGA-DA-A3F3	SKCM	TCGA	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.6471
p.P136L	DO37607	SKCM	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.6471
p.T313M	TCGA-DF-A2KU	UCEC	TCGA	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.7423
p.T313M	TCGA-FI-A2F4	UCEC	TCGA	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.7423
p.T313M	DO43434	UCEC	ICGC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.7423
p.T313M	DO223286	UCEC	ICGC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.7423
p.P126H	TCGA-EE-A2MC	SKCM	TCGA	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation rewiring degron network	0.0556
p.P126H	DO37559	SKCM	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation rewiring degron network	0.0556
p.S141F	TCGA-FS-A1ZK	SKCM	TCGA	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.7982
p.S141F	DO37474	SKCM	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.7982
p.E326K	TCGA-GC-A3I6	BLCA	TCGA	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation rewiring degron network	0.0833
p.E326K	DO844	BLCA	ICGC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation rewiring degron network	0.0833
p.K145N	TCGA-MA-AA42	CESC	TCGA	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation rewiring degron network	0.2778
p.K145N	DO219724	CESC	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation rewiring degron network	0.2778
p.V150L	DO1140	BRCA	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation rewiring degron network	0.1389
p.T139I	DO222794	COCA	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.8189
p.S141Y	DO23260	LINC	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.712
p.S141Y	SIDM00321	Ovarian Carcinoma	GDSC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.712
p.S141Y	ACH-000430	Ovarian Cancer	CCLE	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.712
p.S141Y	TYK-nu	ovary	COSMIC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.712
p.P136A	DO228872	MALY	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.7503
p.R137Q	DO220851	MELA	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.6218
p.R137Q	ACH-000831	Endometrial/Uterine Cancer	CCLE	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.6218
p.W134G	DO229229	THCA	ICGC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation rewiring degron network	0.2778
p.F153I	SIDM01953	Colorectal Carcinoma	GDSC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation rewiring degron network	0.0556
p.T316I	SIDM01183	Other Solid Cancers	GDSC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.5966
p.T316I	ACH-001417	Lung Cancer	CCLE	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.5966
p.T316I	UMC-11	lung	COSMIC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.5966
p.P308L	SIDM01161	Other Sarcomas	GDSC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation rewiring degron network	0.25
p.R101H	SIDM00333	Endometrial Carcinoma	GDSC	DSGNYS	DEG_SCF_TRCP1_1	90:95	Mutation rewiring degron network	0.1667
p.R101H	ACH-000988	Endometrial/Uterine Cancer	CCLE	DSGNYS	DEG_SCF_TRCP1_1	90:95	Mutation rewiring degron network	0.1667
p.R101H	MFE-319	endometrium	COSMIC	DSGNYS	DEG_SCF_TRCP1_1	90:95	Mutation rewiring degron network	0.1667
p.Y94H	SIDM00878	Breast Carcinoma	GDSC	DSGNYS	DEG_SCF_TRCP1_1	90:95	Mutation altering degron motif	0.6118
p.Y94H	ACH-000930	Breast Cancer	CCLE	DSGNYS	DEG_SCF_TRCP1_1	90:95	Mutation altering degron motif	0.6118
p.P140Q	SIDM00999	Bladder Carcinoma	GDSC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.7035
p.P140Q	ACH-000973	Bladder Cancer	CCLE	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.7035
p.P140Q	639-V	urinary tract	COSMIC	PRSTPSLT	DEG_SCF_FBW7_1	136:143	Mutation altering degron motif	0.7035
p.M311T	SIDM00302	Other Solid Cancers	GDSC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.7423
p.M311T	SIDM00163	Biliary Tract Carcinoma	GDSC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.7423
p.M311T	ACH-000461	Bile Duct Cancer	CCLE	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.7423
p.M311T	ACH-002149	Ovarian Cancer	CCLE	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.7423
p.M311T	KGN	ovary	COSMIC	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation altering degron motif	0.7423
p.E305Q	ACH-001347	Head and Neck Cancer	CCLE	MGTPWTE	DEG_SCF_FBW7_2	311:317	Mutation rewiring degron network	0.1667

Kaplan plot for IL6R in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

IL6R

UniProt ID: P08887

Entrez ID: 3570

Protein name: Interleukin-6 receptor subunit alpha (IL-6 receptor subunit alpha) (IL-6R subunit alpha) (IL-6R-alpha) (IL-6RA) (IL-6R 1) (Membrane glycoprotein 80) (gp80) (CD antigen CD126) [Cleaved into: Soluble interleukin-6 receptor subunit alpha (sIL6R)]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IL6R in