ID IL6_DELLE Reviewed; 208 AA.
AC Q9XT80;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 27-MAR-2024, entry version 86.
DE RecName: Full=Interleukin-6;
DE Short=IL-6;
DE Flags: Precursor;
GN Name=IL6;
OS Delphinapterus leucas (Beluga whale).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Whippomorpha; Cetacea; Odontoceti;
OC Monodontidae; Delphinapterus.
OX NCBI_TaxID=9749;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10678396; DOI=10.1016/s0165-2427(99)00150-6;
RA St Laurent G., Archambault D.;
RT "Molecular cloning, phylogenetic analysis and expression of beluga whale
RT (Delphinapterus leucas) interleukin 6.";
RL Vet. Immunol. Immunopathol. 73:31-44(2000).
CC -!- FUNCTION: Cytokine with a wide variety of biological functions in
CC immunity, tissue regeneration, and metabolism. Binds to IL6R, then the
CC complex associates to the signaling subunit IL6ST/gp130 to trigger the
CC intracellular IL6-signaling pathway. The interaction with the membrane-
CC bound IL6R and IL6ST stimulates 'classic signaling', whereas the
CC binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'.
CC Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R
CC complexes on transmitter cells activate IL6ST receptors on neighboring
CC receiver cells. {ECO:0000250|UniProtKB:P05231}.
CC -!- FUNCTION: IL6 is a potent inducer of the acute phase response. Rapid
CC production of IL6 contributes to host defense during infection and
CC tissue injury, but excessive IL6 synthesis is involved in disease
CC pathology. In the innate immune response, is synthesized by myeloid
CC cells, such as macrophages and dendritic cells, upon recognition of
CC pathogens through toll-like receptors (TLRs) at the site of infection
CC or tissue injury (By similarity). In the adaptive immune response, is
CC required for the differentiation of B cells into immunoglobulin-
CC secreting cells. Plays a major role in the differentiation of CD4(+) T
CC cell subsets. Essential factor for the development of T follicular
CC helper (Tfh) cells that are required for the induction of germinal-
CC center formation. Required to drive naive CD4(+) T cells to the Th17
CC lineage. Also required for proliferation of myeloma cells and the
CC survival of plasmablast cells (By similarity).
CC {ECO:0000250|UniProtKB:P05231, ECO:0000250|UniProtKB:P08505}.
CC -!- FUNCTION: Acts as an essential factor in bone homeostasis and on
CC vessels directly or indirectly by induction of VEGF, resulting in
CC increased angiogenesis activity and vascular permeability. Induces,
CC through 'trans-signaling' and synergistically with IL1B and TNF, the
CC production of VEGF. Involved in metabolic controls, is discharged into
CC the bloodstream after muscle contraction increasing lipolysis and
CC improving insulin resistance (By similarity). 'Trans-signaling' in
CC central nervous system also regulates energy and glucose homeostasis.
CC Mediates, through GLP-1, crosstalk between insulin-sensitive tissues,
CC intestinal L cells and pancreatic islets to adapt to changes in insulin
CC demand (By similarity). Also acts as a myokine (By similarity). Plays a
CC protective role during liver injury, being required for maintenance of
CC tissue regeneration (By similarity). Also has a pivotal role in iron
CC metabolism by regulating HAMP/hepcidin expression upon inflammation or
CC bacterial infection (By similarity). Through activation of IL6ST-YAP-
CC NOTCH pathway, induces inflammation-induced epithelial regeneration (By
CC similarity). {ECO:0000250|UniProtKB:P05231,
CC ECO:0000250|UniProtKB:P08505}.
CC -!- SUBUNIT: Component of a hexamer of two molecules each of IL6, IL6R and
CC IL6ST; first binds to IL6R to associate with the signaling subunit
CC IL6ST. Interacts with IL6R (via the N-terminal ectodomain); this
CC interaction may be affected by IL6R-binding with SORL1, hence
CC decreasing IL6 cis signaling. Interacts with SORL1 (via the N-terminal
CC ectodomain); this interaction leads to IL6 internalization and
CC lysosomal degradation. May form a trimeric complex with the soluble
CC SORL1 ectodomain and soluble IL6R receptor; this interaction might
CC stabilize circulating IL6, hence promoting IL6 trans signaling.
CC {ECO:0000250|UniProtKB:P05231}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P05231}.
CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
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DR EMBL; AF076643; AAD42929.1; -; mRNA.
DR AlphaFoldDB; Q9XT80; -.
DR SMR; Q9XT80; -.
DR STRING; 9749.Q9XT80; -.
DR GlyCosmos; Q9XT80; 1 site, No reported glycans.
DR InParanoid; Q9XT80; -.
DR Proteomes; UP000248483; Unplaced.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005138; F:interleukin-6 receptor binding; IEA:InterPro.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0072574; P:hepatocyte proliferation; ISS:UniProtKB.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; ISS:UniProtKB.
DR GO; GO:0051240; P:positive regulation of multicellular organismal process; IEA:UniProt.
DR GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; ISS:UniProtKB.
DR GO; GO:0070092; P:regulation of glucagon secretion; ISS:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0014823; P:response to activity; ISS:UniProtKB.
DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISS:UniProtKB.
DR GO; GO:0010573; P:vascular endothelial growth factor production; ISS:UniProtKB.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR003574; IL-6-like.
DR InterPro; IPR030474; IL-6/GCSF/MGF.
DR InterPro; IPR030473; IL6/GCSF/MGF_CS.
DR PANTHER; PTHR48406; INTERLEUKIN-6; 1.
DR PANTHER; PTHR48406:SF1; INTERLEUKIN-6; 1.
DR Pfam; PF00489; IL6; 1.
DR PIRSF; PIRSF001935; IL6_MGF_GCSF; 1.
DR PRINTS; PR00433; IL6GCSFMGF.
DR PRINTS; PR00434; INTERLEUKIN6.
DR SMART; SM00126; IL6; 1.
DR SUPFAM; SSF47266; 4-helical cytokines; 1.
DR PROSITE; PS00254; INTERLEUKIN_6; 1.
PE 2: Evidence at transcript level;
KW Acute phase; Cytokine; Disulfide bond; Glycoprotein; Growth factor;
KW Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..208
FT /note="Interleukin-6"
FT /id="PRO_0000015579"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05231"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 67..73
FT /evidence="ECO:0000250"
FT DISULFID 96..106
FT /evidence="ECO:0000250"
SQ SEQUENCE 208 AA; 23456 MW; 81CC85C6E80389C4 CRC64;
MNSLSTIAFS LGLLLVTATA FPTPGPLGED FKDDTTSDRL LLTSPDKTEA LIKYILGKIS
AMRKEMCEKY DKCENSKEAL AENNLNLPKM AEKDGCFQSG FNQETCLMRI TTGLLEYQIY
LDYLQNEYEG DKGSIEAVQI SIKALAQILR QKVKNPDEVT TPDPTTNASL MNNLQSQNDD
WMRNTKIILI LRSLENFLQF SLRAVRIK
//
