Details of Protein

General Information of Protein (ID: PRT00095)
Name Interleukin-6 (IL6)
Synonyms   Click to Show/Hide Synonyms of This Protein
IL-6; B-cell stimulatory factor 2; BSF-2; CTL differentiation factor; CDF; Hybridoma growth factor; Interferon beta-2; IFN-beta-2; IL6; IFNB2
Gene Name IL6 Gene ID
3569
UniProt ID
P05231
Family Interleukin (IL)
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI
LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL
EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ
AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM
Structure
1ALU ; 1IL6 ; 1N2Q ; 1P9M ; 2IL6 ; 4CNI ; 4J4L ; 4NI7 ; 4NI9 ; 4O9H ; 4ZS7 ; 5FUC
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).; 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.; 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 also 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 (Probable). 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) Regulating This Protein
      Organic acids and derivatives
            Gamma-Glutamylvaline 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 Gamma-Glutamylvaline addition (2 hours)
                      Induced Change IL6 protein expression levels: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Peritonitis [ICD-11: DC50]
                      Details It is reported that gamma-glutamylvaline addition causes the decrease of IL6 protein expression compared with control group.
            Glutamine 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 Glutamine addition (18 hours)
                      Induced Change IL6 protein expression levels: decrease (FC = 1.2)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Inflammatory bowel disease [ICD-11: DD72]
                      Details It is reported that glutamine addition causes the decrease of IL6 protein expression compared with control group.
      Organic oxygen compounds
            L-Galactose 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 [3]
                      Introduced Variation L-Galactose addition (4 hours)
                      Induced Change IL6 mRNA levels: increase (FC = 2.6)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that L-galactose addition causes the increase of IL6 mRNA levels compared with control group.
References
1 Dietary -Glutamyl Valine Ameliorates TNF--Induced Vascular Inflammation via Endothelial Calcium-Sensing Receptors. J Agric Food Chem. 2020 Aug 26;68(34):9139-9149.
2 Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut. Clin Nutr. 2003 Aug;22(4):407-13.
3 Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS. Cell. 2019 Jun 27;178(1):176-189.e15.

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