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Showing Protein Interleukin-6 (HMDBP14617)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP14617
Secondary Accession Numbers None
Name Interleukin-6
Synonyms
  1. IL-6
  2. B-cell hybridoma growth factor
  3. Interleukin HP-1
Gene Name IL6
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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 (PubMed:8910279). 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 (PubMed:27893700).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 (PubMed:23045607). Required to drive naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells (PubMed:16990136, PubMed:27893700). 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 (PubMed:17075861). Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (PubMed:11786910). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (PubMed:28402851). Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (PubMed:11113088). Also acts as a myokine (By similarity). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (PubMed:11113088, PubMed:8910279). 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).
Pathways
  • African trypanosomiasis
  • AGE-RAGE signaling pathway in diabetic complications
  • Alzheimer disease
  • Amoebiasis
  • Antifolate resistance
  • C-type lectin receptor signaling pathway
  • Cellular senescence
  • Chagas disease
  • Coronavirus disease - COVID-19
  • Cytokine-cytokine receptor interaction
  • Cytosolic DNA-sensing pathway
  • EGFR tyrosine kinase inhibitor resistance
  • Epstein-Barr virus infection
  • FoxO signaling pathway
  • Graft-versus-host disease
  • Hematopoietic cell lineage
  • Hepatitis B
  • Herpes simplex virus 1 infection
  • HIF-1 signaling pathway
  • Human cytomegalovirus infection
  • Human T-cell leukemia virus 1 infection
  • Hypertrophic cardiomyopathy
  • IL-17 signaling pathway
  • Inflammatory bowel disease
  • Influenza A
  • Insulin resistance
  • Intestinal immune network for IgA production
  • JAK-STAT signaling pathway
  • Kaposi sarcoma-associated herpesvirus infection
  • Legionellosis
  • Lipid and atherosclerosis
  • Malaria
  • Measles
  • NOD-like receptor signaling pathway
  • Non-alcoholic fatty liver disease
  • Pathways of neurodegeneration - multiple diseases
  • Pertussis
  • PI3K-Akt signaling pathway
  • Prion disease
  • Rheumatoid arthritis
  • Salmonella infection
  • Th17 cell differentiation
  • TNF signaling pathway
  • Toll-like receptor signaling pathway
  • Transcriptional misregulation in cancer
  • Tuberculosis
  • Viral protein interaction with cytokine and cytokine receptor
  • Yersinia infection
Reactions Not Available
GO Classification
Biological Process
cell redox homeostasis
positive regulation vascular endothelial growth factor production
wound healing
regulation of cell proliferation
gene expression
positive regulation of chemokine production
positive regulation of DNA replication
muscle cell homeostasis
positive regulation of production of miRNAs involved in gene silencing by miRNA
positive regulation of apoptotic process
negative regulation of bone resorption
regulation of cell shape
positive regulation of immunoglobulin production
positive regulation of interleukin-10 production
positive regulation of interleukin-8 production
negative regulation of gluconeogenesis
response to amino acid stimulus
response to electrical stimulus
myeloid cell homeostasis
positive regulation of cell proliferation
negative regulation of apoptotic process
response to heat
negative regulation of collagen biosynthetic process
positive regulation of tyrosine phosphorylation of STAT protein
bone remodeling
positive regulation of B cell activation
positive regulation of protein import into nucleus
positive regulation of T cell proliferation
response to calcium ion
inflammatory response
positive regulation of neuron differentiation
acute-phase response
response to wounding
neuron projection development
negative regulation of chemokine production
response to auditory stimulus
cellular response to tumor necrosis factor
response to insulin stimulus
cellular response to virus
endocrine pancreas development
response to drug
cellular response to estradiol stimulus
positive regulation of epithelial to mesenchymal transition
positive regulation of interleukin-17 production
negative regulation of hormone secretion
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of nitric oxide biosynthetic process
cellular response to lipopolysaccharide
cellular response to interleukin-1
positive regulation of translation
regulation of glucagon secretion
positive regulation of ERK1 and ERK2 cascade
positive regulation of peptidyl-tyrosine phosphorylation
response to glucocorticoid stimulus
positive regulation of sequence-specific DNA binding transcription factor activity
glucose homeostasis
defense response to virus
cellular response to hepatocyte growth factor stimulus
cellular response to prolactin
positive regulation of transcription, DNA-dependent
epithelial cell proliferation involved in salivary gland morphogenesis
positive regulation of neuron projection development
glucagon secretion
hepatic immune response
hepatocyte proliferation
liver regeneration
lymphocyte costimulation
negative regulation of interleukin-1-mediated signaling pathway
negative regulation of membrane potential
negative regulation of muscle organ development
negative regulation of neuron death
positive regulation of protein kinase B signaling cascade
negative regulation of primary miRNA processing
neutrophil apoptotic process
positive regulation of transcription from RNA polymerase II promoter
positive regulation of apoptotic DNA fragmentation
positive regulation of cell proliferation in bone marrow
positive regulation of extracellular matrix disassembly
positive regulation of interleukin-21 production
positive regulation of leukocyte adhesion to vascular endothelial cell
positive regulation of receptor signaling pathway via STAT
positive regulation of T-helper 2 cell cytokine production
positive regulation of T-helper 2 cell differentiation
positive regulation of glial cell proliferation
positive regulation of transmission of nerve impulse
regulation of circadian sleep/wake cycle, non-REM sleep
regulation of vascular endothelial growth factor production
T follicular helper cell differentiation
T-helper 17 cell lineage commitment
regulation of apoptotic process
vascular endothelial growth factor production
positive regulation of gliogenesis
cellular response to nutrient levels
cytokine-mediated signaling pathway
positive regulation of MAPK cascade
positive regulation of osteoblast differentiation
response to activity
positive regulation of tumor necrosis factor production
interleukin-6-mediated signaling pathway
response to antibiotic
positive regulation of epithelial cell proliferation
aging
defense response to protozoan
germinal center B cell differentiation
positive regulation of acute inflammatory response
negative regulation of cell proliferation
positive regulation of cytokine production involved in inflammatory response
response to caffeine
positive regulation of interleukin-1 beta production
positive regulation of interleukin-6 production
positive regulation of gene expression
regulation of insulin secretion
cellular response to dexamethasone stimulus
cellular response to hydrogen peroxide
positive regulation of smooth muscle cell proliferation
T cell activation
positive regulation of peptidyl-serine phosphorylation
positive regulation of receptor signaling pathway via JAK-STAT
branching involved in salivary gland morphogenesis
response to cold
negative regulation of protein kinase activity
response to yeast
Cellular Component
cytoplasm
interleukin-6 receptor complex
extracellular space
external side of plasma membrane
Molecular Function
interleukin-6 receptor binding
growth factor activity
receptor binding
cytokine activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 211
Molecular Weight 24383.76
Theoretical pI 7.415
Pfam Domain Function
Signals
  • 1-24;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P08505
UniProtKB/Swiss-Prot Entry Name IL6_MOUSE
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  5. Chiu CP, Moulds C, Coffman RL, Rennick D, Lee F: Multiple biological activities are expressed by a mouse interleukin 6 cDNA clone isolated from bone marrow stromal cells. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7099-103. doi: 10.1073/pnas.85.19.7099. [PubMed:3262872 ]
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  7. Blankenstein T, Qin ZH, Li WQ, Diamantstein T: DNA rearrangement and constitutive expression of the interleukin 6 gene in a mouse plasmacytoma. J Exp Med. 1990 Mar 1;171(3):965-70. doi: 10.1084/jem.171.3.965. [PubMed:2106569 ]
  8. Mock BA, Nordan RP, Justice MJ, Kozak C, Jenkins NA, Copeland NG, Clark SC, Wong GG, Rudikoff S: The murine Il-6 gene maps to the proximal region of chromosome 5. J Immunol. 1989 Feb 15;142(4):1372-6. [PubMed:2563387 ]
  9. Van Snick J, Cayphas S, Vink A, Uyttenhove C, Coulie PG, Rubira MR, Simpson RJ: Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9679-83. doi: 10.1073/pnas.83.24.9679. [PubMed:2948184 ]
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  13. Peters M, Blinn G, Jostock T, Schirmacher P, Meyer zum Buschenfelde KH, Galle PR, Rose-John S: Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration. Gastroenterology. 2000 Dec;119(6):1663-71. doi: 10.1053/gast.2000.20236. [PubMed:11113088 ]
  14. Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO: Interleukin-6-deficient mice develop mature-onset obesity. Nat Med. 2002 Jan;8(1):75-9. doi: 10.1038/nm0102-75. [PubMed:11786910 ]
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  20. Kang S, Tanaka T, Narazaki M, Kishimoto T: Targeting Interleukin-6 Signaling in Clinic. Immunity. 2019 Apr 16;50(4):1007-1023. doi: 10.1016/j.immuni.2019.03.026. [PubMed:30995492 ]