Details of Protein

General Information of Protein (ID: PRT00077)
Name Interleukin-6 (IL6)
Synonyms   Click to Show/Hide Synonyms of This Protein
IL-6; B-cell hybridoma growth factor; Interleukin HP-1; Il6; Il-6
Gene Name Il6 Gene ID
16193
UniProt ID
P08505
Family Interleukin (IL)
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MKFLSARDFHPVAFLGLMLVTTTAFPTSQVRRGDFTEDTTPNRPVYTTSQVGGLITHVLW
EIVEMRKELCNGNSDCMNNDDALAENNLKLPEIQRNDGCYQTGYNQEICLLKISSGLLEY
HSYLEYMKNNLKDNKKDKARVLQRDTETLIHIFNQEVKDLHKIVLPTPISNALLTDKLES
QKEWLRTKTIQFILKSLEEFLKVTLRSTRQT
Structure
2L3Y
Function Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway. 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.; 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. In the adaptive immune response, is required for the differentiation of B-cells into immunoglolin-secreting cells (Probable). 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. Together with IL21, controls the early generation of Tfh cells and are critical for an effective antibody response to acute viral infection. Required to drive naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells. Also required for proliferation of myeloma cells and the survival of plasmablast cells (Probable).; 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. Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF. Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance. 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis. Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. Also acts as a myokine. Plays a protective role during liver injury, being required for maintenance of tissue regeneration. Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection. Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration.
Regulatory Network
Full List of Metabolite(s) Regulated by This Protein
      Organic oxygen compounds
            Glucose Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Knockout of IL6
                      Induced Change Glucose concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of IL6 leads to the increase of glucose levels compared with control group.
Full List of Metabolite(s) Regulating This Protein
      Organic acids
            Sodium oxamate Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Sodium oxamate addition (4 hours)
                      Induced Change IL6 mRNA levels: increase (FC = 3)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Acute lymphoblastic leukemia [ICD-11: 2B33]
                      Details It is reported that sodium oxamate addition causes the increase of IL6 mRNA levels compared with control group.
References
1 IL-6 deficiency in mice neither impairs induction of metabolic genes in the liver nor affects blood glucose levels during fasting and moderately intense exercise. Diabetologia. 2010 Aug;53(8):1732-42.
2 Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS. Cell. 2019 Jun 27;178(1):176-189.e15.

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