DegronMD - P40189(IL6ST)

FUNCTION: Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates the intracellular JAK-MAPK and JAK-STAT3 signaling pathways (PubMed:2261637, PubMed:19915009, PubMed:23294003). That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3 (PubMed:19915009, PubMed:23294003, PubMed:25731159). In parallel, the IL6 signaling pathway induces the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (By similarity). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (By similarity). Acts as a receptor for the neuroprotective peptide humanin as part of a complex with IL27RA/WSX1 and CNTFR (PubMed:19386761). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity). {ECO:0000250|UniProtKB:Q00560, ECO:0000269|PubMed:19386761, ECO:0000269|PubMed:19915009, ECO:0000269|PubMed:2261637, ECO:0000269|PubMed:23294003, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:28747427, ECO:0000269|PubMed:30309848}.; FUNCTION: [Isoform 2]: Binds to the soluble IL6:sIL6R complex (hyper-IL6), thereby blocking IL6 trans-signaling. Inhibits sIL6R-dependent acute phase response (PubMed:11121117, PubMed:21990364, PubMed:30279168). Also blocks IL11 cluster signaling through IL11R (PubMed:30279168). {ECO:0000269|PubMed:11121117, ECO:0000269|PubMed:21990364, ECO:0000269|PubMed:30279168}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.H669L	TCGA-55-8616	LUAD	TCGA	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.0556
p.N677I	TCGA-A4-A5DU	KIRP	TCGA	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.2778
p.Q681K	TCGA-A5-A0G2	UCEC	TCGA	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation altering degron motif	0.5833
p.S279C	TCGA-BH-A0WA	BRCA	TCGA	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.0556
p.S279C	DO2897	BRCA	ICGC	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.0556
p.R281Q	TCGA-EO-A3AV	UCEC	TCGA	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.1111
p.R281Q	DO52412	UCEC	ICGC	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.1111
p.S279F	TCGA-ER-A19E	SKCM	TCGA	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.0556
p.S279F	TCGA-ZF-AA58	BLCA	TCGA	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.0556
p.S279F	DO219100	BLCA	ICGC	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.0556
p.S279F	DO47542	SKCM	ICGC	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.0556
p.R300H	TCGA-QK-A8ZB	HNSC	TCGA	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.1667
p.R300H	DO52100	HNSC	ICGC	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.1667
p.E695K	TCGA-ZF-AA53	BLCA	TCGA	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.0556
p.E695K	DO219096	BLCA	ICGC	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.0556
p.S282F	DO222504	MELA	ICGC	LKPFTE	LIG_APCC_ABBA_1	289:294	Mutation rewiring degron network	0.1389
p.S671L	DO48547	STAD	ICGC	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.1111
p.S671L	IM-95	stomach	COSMIC	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.1111
p.N675S	SIDM00364	B-Lymphoblastic Leukemia	GDSC	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.2222
p.N675S	ACH-002059	Leukemia	CCLE	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.2222
p.N675S	P30-OHK	haematopoietic and lymphoid tissue	COSMIC	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.2222
p.T689I	SIDM00837	Colorectal Carcinoma	GDSC	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.2222
p.T689I	ACH-000958	Colon/Colorectal Cancer	CCLE	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.2222
p.T689I	SW48	large intestine	COSMIC	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.2222
p.S688P	SW13	adrenal gland	COSMIC	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.25
p.G669R	JHOS-3	ovary	COSMIC	KDQMYSD	LIG_APCC_ABBAyCdc20_2	679:685	Mutation rewiring degron network	0.0556

Kaplan plot for IL6ST in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

IL6ST

UniProt ID: P40189

Entrez ID: 3572

Protein name: Interleukin-6 receptor subunit beta (IL-6 receptor subunit beta) (IL-6R subunit beta) (IL-6R-beta) (IL-6RB) (CDw130) (Interleukin-6 signal transducer) (Membrane glycoprotein 130) (gp130) (Oncostatin-M receptor subunit alpha) (CD antigen CD130)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IL6ST in