DegronMD - P05231(IL6)

FUNCTION: Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', 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:0000305|PubMed:30995492}.; FUNCTION: IL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury (Probable). In the adaptive immune response, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4(+) T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4(+) T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells (By similarity). {ECO:0000250|UniProtKB:P08505, ECO:0000305|PubMed:30995492}.; FUNCTION: Acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability (PubMed:17075861, PubMed:12794819). Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF (PubMed:12794819). Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (PubMed:20823453). 'Trans-signaling' in central nervous system also regulates energy and glucose homeostasis (By similarity). Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (By similarity). Also acts as a myokine (Probable). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection (PubMed:15124018). Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity). {ECO:0000250|UniProtKB:P08505, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:15124018, ECO:0000269|PubMed:17075861, ECO:0000269|PubMed:20823453, ECO:0000305|PubMed:30995492}. View more >>

GO - Biological processes (BP): acute-phase response [GO:0006953]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to virus [GO:0098586]; cytokine-mediated signaling pathway [GO:0019221]; defense response to Gram-negative bacterium [GO:0050829]; defense response to Gram-positive bacterium [GO:0050830]; defense response to virus [GO:0051607]; endocrine pancreas development [GO:0031018]; germinal center B cell differentiation [GO:0002314]; glucagon secretion [GO:0070091]; glucose homeostasis [GO:0042593]; hepatic immune response [GO:0002384]; hepatocyte proliferation [GO:0072574]; humoral immune response [GO:0006959]; inflammatory response [GO:0006954]; interleukin-6-mediated signaling pathway [GO:0070102]; liver regeneration [GO:0097421]; maintenance of blood-brain barrier [GO:0035633]; monocyte chemotaxis [GO:0002548]; negative regulation of apoptotic process [GO:0043066]; negative regulation of bone resorption [GO:0045779]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of chemokine production [GO:0032682]; negative regulation of collagen biosynthetic process [GO:0032966]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of interleukin-1-mediated signaling pathway [GO:2000660]; negative regulation of lipid storage [GO:0010888]; negative regulation of neurogenesis [GO:0050768]; negative regulation of primary miRNA processing [GO:2000635]; neuron cellular homeostasis [GO:0070050]; neuron projection development [GO:0031175]; neutrophil apoptotic process [GO:0001781]; neutrophil mediated immunity [GO:0002446]; platelet activation [GO:0030168]; positive regulation of acute inflammatory response [GO:0002675]; positive regulation of apoptotic DNA fragmentation [GO:1902512]; positive regulation of apoptotic process [GO:0043065]; positive regulation of B cell activation [GO:0050871]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of chemokine production [GO:0032722]; positive regulation of cytokine production involved in inflammatory response [GO:1900017]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of epithelial to mesenchymal transition [GO:0010718]; positive regulation of extracellular matrix disassembly [GO:0090091]; positive regulation of gene expression [GO:0010628]; positive regulation of glial cell proliferation [GO:0060252]; positive regulation of immunoglobulin production [GO:0002639]; positive regulation of interleukin-10 production [GO:0032733]; positive regulation of interleukin-17 production [GO:0032740]; positive regulation of interleukin-1 beta production [GO:0032731]; positive regulation of interleukin-21 production [GO:0032745]; positive regulation of interleukin-6 production [GO:0032755]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of leukocyte adhesion to vascular endothelial cell [GO:1904996]; positive regulation of leukocyte chemotaxis [GO:0002690]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of neuroinflammatory response [GO:0150078]; positive regulation of osteoblast differentiation [GO:0045669]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of platelet aggregation [GO:1901731]; positive regulation of production of miRNAs involved in gene silencing by miRNA [GO:1903800]; positive regulation of receptor signaling pathway via JAK-STAT [GO:0046427]; positive regulation of receptor signaling pathway via STAT [GO:1904894]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of T cell proliferation [GO:0042102]; positive regulation of T-helper 2 cell cytokine production [GO:2000553]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of translation [GO:0045727]; positive regulation of tumor necrosis factor production [GO:0032760]; positive regulation of type B pancreatic cell apoptotic process [GO:2000676]; positive regulation of tyrosine phosphorylation of STAT protein [GO:0042531]; positive regulation of vascular endothelial growth factor production [GO:0010575]; regulation of angiogenesis [GO:0045765]; regulation of astrocyte activation [GO:0061888]; regulation of glucagon secretion [GO:0070092]; regulation of insulin secretion [GO:0050796]; regulation of microglial cell activation [GO:1903978]; regulation of neuroinflammatory response [GO:0150077]; regulation of vascular endothelial growth factor production [GO:0010574]; response to activity [GO:0014823]; response to glucocorticoid [GO:0051384]; response to peptidoglycan [GO:0032494]; T follicular helper cell differentiation [GO:0061470]; T-helper 17 cell lineage commitment [GO:0072540]; vascular endothelial growth factor production [GO:0010573] 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.D162E	DO229489	LAML	ICGC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01265	Plasma Cell Myeloma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01020	Plasma Cell Myeloma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00253	Neuroblastoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00234	Other Solid Cancers	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00330	Neuroblastoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01237	Hepatocellular Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00565	Oral Cavity Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00547	Non-Small Cell Lung Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00262	Ewing's Sarcoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00057	Neuroblastoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00328	Esophageal Squamous Cell Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01201	Other Blood Cancers	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00552	Rhabdomyosarcoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00155	Head and Neck Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00354	Squamous Cell Lung Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01247	Burkitt's Lymphoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00292	Small Cell Lung Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01180	Hepatocellular Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00516	Melanoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00674	Non-Cancerous	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00247	Gastric Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00887	Other Solid Cancers	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01049	Non-Cancerous	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01029	Esophageal Squamous Cell Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00438	B-Lymphoblastic Leukemia	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00018	Acute Myeloid Leukemia	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01061	Oral Cavity Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00271	Gastric Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00613	Glioblastoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00999	Bladder Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00361	Non-Small Cell Lung Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01025	Esophageal Squamous Cell Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01879	Non-Cancerous	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01059	Melanoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00381	Cervical Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00359	Colorectal Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01449	Pancreatic Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM00017	Squamous Cell Lung Carcinoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.D162E	SIDM01494	Glioblastoma	GDSC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.L175R	DO230950	LUSC	ICGC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.1944
p.L175R	DO224638	LUSC	ICGC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.1944
p.R173H	SNU-81	large intestine	COSMIC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.25
p.V160E	JEG-3	placenta	COSMIC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2222
p.W162R	SNU-C5	large intestine	COSMIC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2778
p.V160A	NCI-H2196	lung	COSMIC	ITTPDPT	DEG_SCF_FBW7_1	164:170	Mutation rewiring degron network	0.2222

Kaplan plot for IL6 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

IL6

UniProt ID: P05231

Entrez ID: 3569

Protein name: Interleukin-6 (IL-6) (B-cell stimulatory factor 2) (BSF-2) (CTL differentiation factor) (CDF) (Hybridoma growth factor) (Interferon beta-2) (IFN-beta-2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IL6 in