Reactome | UniProt:P05231 IL6

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UniProt:P05231 IL6 Show undefined attributes

chain	signal peptide:1-29 chain:30-212
checksum	1F1ED1FE1B734079
comment	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).FUNCTION 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).FUNCTION 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 (PubMed:12794819, PubMed:17075861). Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF (PubMed:12794819). Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (PubMed:20823453). '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 (PubMed:15124018). Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity).SUBUNIT Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6R to associate with the signaling subunit IL6ST (PubMed:12829785). Interacts with IL6R (via the N-terminal ectodomain); this interaction may be affected by IL6R-binding with SORL1, hence decreasing IL6 cis signaling (PubMed:28265003). Interacts with SORL1 (via the N-terminal ectodomain); this interaction leads to IL6 internalization and lysosomal degradation (PubMed:28265003). May form a trimeric complex with the soluble SORL1 ectodomain and soluble IL6R receptor; this interaction might stabilize circulating IL6, hence promoting IL6 trans signaling (PubMed:28265003).INTERACTION Produced by skeletal muscle.INDUCTION Plasma levels are highly increased upon exercise, due to enhanced production by contracting skeletal muscles. Up-regulated by coagulation factor Xa (F10) in PAR-1 (F2R)-dependent manner in cardiac fibroblasts (PubMed:34831181).PTM N- and O-glycosylated.POLYMORPHISM Genetic variations in IL6 may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men.SIMILARITY Belongs to the IL-6 superfamily.ONLINE INFORMATION Interleukin-6 entry
crossReference	[DatabaseIdentifier:12232245] PDB:7NXZ [DatabaseIdentifier:12347630] RefSeq:NP_000591.1 [DatabaseIdentifier:12347631] RefSeq:XP_054214121.1 [DatabaseIdentifier:12293990] Pharos - Targets:P05231 [DatabaseIdentifier:12256219] PRO:P05231 [DatabaseIdentifier:12232246] PDB:8YWR [DatabaseIdentifier:12232249] PDB:4CNI [DatabaseIdentifier:11463390] ENSEMBL:ENSG00000136244 [DatabaseIdentifier:11557892] ENSEMBL:ENSP00000385675 [DatabaseIdentifier:11557893] ENSEMBL:ENSP00000258743 [DatabaseIdentifier:11680592] ENSEMBL:ENST00000258743 [DatabaseIdentifier:11680591] ENSEMBL:ENST00000404625 [DatabaseIdentifier:11796164] GeneCards:IL6 [DatabaseIdentifier:11811885] GlyGen:P05231 [DatabaseIdentifier:11833262] HMDB Protein:HMDBP02087 [DatabaseIdentifier:11849131] HPA:ENSG00000136244-IL6 [DatabaseIdentifier:12133824] OpenTargets:ENSG00000136244 [DatabaseIdentifier:12137411] Orphanet:IL6 [DatabaseIdentifier:12221496] PDB:5FUC [DatabaseIdentifier:12232248] PDB:4NI7 [DatabaseIdentifier:12232250] PDB:4NI9 [DatabaseIdentifier:12166603] PDB:8QY6 [DatabaseIdentifier:12232252] PDB:4ZS7 [DatabaseIdentifier:12142103] PDB:8D82 [DatabaseIdentifier:12232254] PDB:2IL6 [DatabaseIdentifier:12232247] PDB:1ALU [DatabaseIdentifier:12232255] PDB:4J4L [DatabaseIdentifier:12232253] PDB:1IL6 [DatabaseIdentifier:12142087] PDB:1P9M [DatabaseIdentifier:12232251] PDB:4O9H [DatabaseIdentifier:12166605] PDB:8QY5 [DatabaseIdentifier:12232244] PDB:8YWQ
databaseName	UniProt
dbId	57279
description	recommendedName: fullName evidence="21"Interleukin-6 shortName: IL-6 alternativeName: B-cell stimulatory factor 2 shortName: BSF-2 alternativeName: CTL differentiation factor shortName: CDF alternativeName: Hybridoma growth factor alternativeName: Interferon beta-2 shortName: IFN-beta-2
displayName	UniProt:P05231 IL6
geneName	IL6 IFNB2
identifier	P05231
isSequenceChanged	false
keyword	3D-structure Acute phase Cytokine Direct protein sequencing Disulfide bond Glycoprotein Growth factor Phosphoprotein Proteomics identification Reference proteome Secreted Signal
modified	[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
moleculeType	Protein
name	IL6
otherIdentifier	11746463_a_at 11760425_a_at 17044177 205207_PM_at 205207_at 2992587 2992588 2992592 2992593 2992594 2992595 2992596 2992597 2992598 2992599 2992600 2992601 2992602 3569 38299_at 8131803 A_14_P133151 A_23_P71037 A_33_P3407013 GE59660 GE84455 GO:0001781 GO:0002314 GO:0002376 GO:0002384 GO:0002446 GO:0002548 GO:0002639 GO:0002675 GO:0002690 GO:0005102 GO:0005125 GO:0005138 GO:0005515 GO:0005576 GO:0005615 GO:0005788 GO:0005896 GO:0006355 GO:0006953 GO:0006954 GO:0006955 GO:0006959 GO:0007165 GO:0007259 GO:0008083 GO:0008284 GO:0008285 GO:0010573 GO:0010574 GO:0010575 GO:0010628 GO:0010718 GO:0010888 GO:0014823 GO:0019221 GO:0030154 GO:0030168 GO:0031018 GO:0031175 GO:0032494 GO:0032682 GO:0032722 GO:0032731 GO:0032733 GO:0032740 GO:0032745 GO:0032755 GO:0032757 GO:0032760 GO:0032966 GO:0033138 GO:0035633 GO:0042102 GO:0042593 GO:0042802 GO:0043065 GO:0043066 GO:0043410 GO:0045599 GO:0045669 GO:0045727 GO:0045765 GO:0045779 GO:0045893 GO:0045944 GO:0046427 GO:0048018 GO:0048661 GO:0048856 GO:0050731 GO:0050768 GO:0050796 GO:0050829 GO:0050830 GO:0050871 GO:0051223 GO:0051240 GO:0051251 GO:0051384 GO:0051607 GO:0060252 GO:0061470 GO:0061888 GO:0070050 GO:0070091 GO:0070092 GO:0070102 GO:0070301 GO:0071222 GO:0072540 GO:0072574 GO:0090091 GO:0090594 GO:0097421 GO:0097696 GO:0098542 GO:0098586 GO:0098772 GO:0150077 GO:0150078 GO:1900017 GO:1901731 GO:1902512 GO:1902895 GO:1903978 GO:1904894 GO:1904996 GO:2000553 GO:2000635 GO:2000660 GO:2000676 HMNXSV003052866 HMNXSV003058441 ILMN_1699651 PH_hs_0026738 TC07000137.hg X04602_s_at Y00081_s_at g10834983_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-447100] IL6 [extracellular region] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-8956764] IL6 [endoplasmic reticulum lumen] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-8957044] p-IL6 [endoplasmic reticulum lumen] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000136244] ENSEMBL:ENSG00000136244 IL6 [ReferenceDNASequence:12680010] UCSC:P05231 IL6 [ReferenceDNASequence:11327770] BioGPS Gene:3569 IL6 [ReferenceDNASequence:11392233] COSMIC - genes:IL6 IL6 [ReferenceDNASequence:11425306] CTD Gene:3569 IL6 [ReferenceDNASequence:11427999] dbSNP Gene:3569 IL6 [ReferenceDNASequence:11827869] HGNC:6018 IL6 [ReferenceDNASequence:11869985] KEGG:hsa:3569 IL6 [ReferenceDNASequence:11957559] Monarch:3569 IL6 [ReferenceDNASequence:12041652] NCBI Gene:3569 IL6 [ReferenceDNASequence:12118054] OMIM:147620 IL6
referenceTranscript	[ReferenceRNASequence:12529489] RefSeq:NM_000600.5 IL6 [ReferenceRNASequence:12529488] RefSeq:XM_054358146.1 IL6
schemaClass	ReferenceGeneProduct
secondaryIdentifier	IL6_HUMAN Q9UCU2 Q9UCU3 Q9UCU4
sequenceLength	212
species	[Species:48887] Homo sapiens
stId	uniprot:P05231
url	http://purl.uniprot.org/uniprot/P05231

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-447100] IL6 [extracellular region] [EntityWithAccessionedSequence:R-HSA-8956764] IL6 [endoplasmic reticulum lumen] [EntityWithAccessionedSequence:R-HSA-8957044] p-IL6 [endoplasmic reticulum lumen]
(referenceSequence)	[ModifiedResidue:8957046] phosphorylated residue at unknown position
(interactor)	[UndirectedInteraction:11216623] UniProt:P40189 <-> UniProt:P05231 (IntAct) [UndirectedInteraction:11239467] UniProt:Q92673 <-> UniProt:P05231 (IntAct) [UndirectedInteraction:11243085] UniProt:P05231 <-> UniProt:P08887 (IntAct) [UndirectedInteraction:11243089] UniProt:P05231 <-> UniProt:P08887-PRO_0000450730 (IntAct) [UndirectedInteraction:11243091] UniProt:P05231 <-> UniProt:Q99523 (IntAct) [UndirectedInteraction:11243093] UniProt:P05231 <-> UniProt:P05231 (IntAct) [UndirectedInteraction:11243093] UniProt:P05231 <-> UniProt:P05231 (IntAct) [UndirectedInteraction:11243095] UniProt:P05231 <-> UniProt:Q05516 (IntAct)

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