General Information of Binding Target of SBP (BTS) (ID: ST00072)
BTS Name
Interleukin-6
Synonyms
IL-6; B-cell stimulatory factor 2; BSF-2; CTL differentiation factor; CDF; Hybridoma growth factor; Interferon beta-2; IFN-beta-2
BTS Type
Protein
Family
IL-6 superfamily
Gene Name
IL6
Organism
Homo sapiens (Human)
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 (By similarity).; 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 (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 Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity).
UniProt ID
P05231
UniProt Entry
IL6_HUMAN
PFam
PF00489
Gene ID
3569
Sequence
MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI
LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL
EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ
AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM
Sequence Length
212
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Affibody anti-IL-6 ZIL-6_13 Research Blocker Kd: 0.5 nM Inflammatory disorders [ICD-11: 4A6Z]
SBP Info
[1]
Avimer AMG220 Phase I; Discontinued Inhibitor Kd: <0.2 nM Crohn disease [ICD-11: DD70]
SBP Info
[2], [3], [4]
Repebody anti-IL-6 B3 Research Binder Kd: 48.8 nM Research tool
SBP Info
[5]
Repebody anti-IL-6 C8 Research Binder Kd: 89.4 nM Research tool
SBP Info
[5]
Repebody anti-IL-6 F11 Research Binder Kd: 117 nM Research tool
SBP Info
[5]
Repebody anti-IL-6 r-D3E8 Research Blocker Kd: 2.5 nM Non-small cell lung cancer [ICD-11: 2C25.Y]
SBP Info
[6]
Repebody anti-IL-6 r-D3E8C4 Research Blocker Kd: 0.4 nM Non-small cell lung cancer [ICD-11: 2C25.Y]
SBP Info
[6]
References
1 An affibody-adalimumab hybrid blocks combined IL-6 and TNF-triggered serum amyloid A secretion in vivo. MAbs. 2014;6(6):1598-607.
2 In vitro-engineered non-antibody protein therapeutics. Protein Cell. 2018 Jan;9(1):3-14.
3 Recent advances in the development of novel protein scaffolds based therapeutics. Int J Biol Macromol. 2017 Sep;102:630-641.
4 Mult ivalent avimer proteins evolved by exon shuffling of a family of human receptor. Nat Biotechnol. 2005 Dec;23(12):1556-61.
5 Design of a binding scaffold based on variable lymphocyte receptors of jawless vertebrates by module engineering. Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3299-304.
6 A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway effectively suppresses non-small cell lung cancer. Mol Ther. 2014 Jul;22(7):1254-1265.