IL6ST
entrez
3572
canonical
uniprot
P40189
canonical
ensembl
ENSG00000134352
resolver
ensp
ENSP00000370694
resolver
ensp
ENSP00000370698
resolver
ensp
ENSP00000435399
resolver
ensp
ENSP00000513851
resolver
ensp
ENSP00000513857
resolver
ensp
ENSP00000513859
resolver
enst
ENST00000698638
resolver
enst
ENST00000698644
resolver
enst
ENST00000698646
resolver
genesymbol
IL6ST
resolver
hgnc
HGNC:6021
resolver
uniprot
A0A0A0N0L2
resolver
uniprot
A0A0A0N0L5
resolver
uniprot
A0A8V8TMJ9
resolver
uniprot
A0A8V8TNI4
resolver
uniprot
A0A8V8TNV0
resolver
uniprot
A0N0L4
resolver
uniprot
Q17RA0
resolver
uniprot
Q5FC04
resolver
uniprot
Q9UQ41
resolver
uniprot_entry
A0A0A0N0L2_HUMAN
resolver
uniprot_entry
A0A0A0N0L5_HUMAN
resolver
uniprot_entry
A0A8V8TMJ9_HUMAN
resolver
uniprot_entry
A0A8V8TNI4_HUMAN
resolver
uniprot_entry
A0A8V8TNV0_HUMAN
resolver
uniprot_entry
IL6RB_HUMAN
resolver
uniprot_entry
Q17RA0_HUMAN
resolver
uniprot_sec
A0N0L4
resolver
uniprot_sec
Q5FC04
resolver
uniprot_sec
Q9UQ41
resolver
amino_acid_sequence
MLTLQTWLVQALFIFLTTESTGELLDPCGYISPESPVVQLHSNFTAVCVLKEKCMDYFHVNANYIVWKTNHFTIPKEQYTIINRTASSVTFTDIASLNIQLTCNILTFGQLEQNVYGITIISGLPPEKPKNLSCIVNEGKKMRCEWDGGRETHLETNFTLKSEWATHKFADCKAKRDTPTSCTVDYSTVYFVNIEVWVEAENALGKVTSDHINFDPVYKVKPNPPHNLSVINSEELSSILKLTWTNPSIKSVIILKYNIQYRTKDASTWSQIPPEDTASTRSSFTVQDLKPFTEYVFRIRCMKEDGKGYWSDWSEEASGITYEDRPSKAPSFWYKIDPSHTQGYRTVQLVWKTLPPFEANGKILDYEVTLTRWKSHLQNYTVNATKLTVNLTNDRYLATLTVRNLVGKSDAAVLTIPACDFQATHPVMDLKAFPKDNMLWVEWTTPRESVKKYILEWCVLSDKAPCITDWQQEDGTVHRTYLRGNLAESKCYLITVTPVYADGPGSPESIKAYLKQAPPSKGPTVRTKKVGKNEAVLEWDQLPVDVQNGFIRNYTIFYRTIIGNETAVNVDSSHTEYTLSSLTSDTLYMVRMAAYTDEGGKDGPEFTFTTPKFAQGEIEAIVVPVCLAFLLTTLLGVLFCFNKRDLIKKHIWPNVPDPSKSHIAQWSPHTPPRHNFNSKDQMYSDGNFTDVSVVEIEANDKKPFPEDLKSLDLFKKEKINTEGHSSGIGGSSCMSSSRPSISSSDENESSQNTSSTVQYSTVVHSGYRHQVPSVQVFSRSESTQPLLDSEERPEDLQLVDHVDGGDGILPRQQYFKQNCSQHESSPDISHFERSKQVSSVNEEDFVRLKQQISDHISQSCGSGQMKMFQEVSAADAFGPGTEGQVERFETVGMEAATDEGMPKSYLPQTVRQGGYMPQ
uniprot
proteins
disease_involvement
DISEASE: Hyper-IgE syndrome 4A, autosomal dominant, with recurrent infections (HIES4A) [MIM:619752]: An immunologic disorder characterized by recurrent mainly sino-pulmonary infections associated with increased serum IgE. Some patients have onset of symptoms in early childhood and develop complications, including bronchiectasis or hemoptysis, whereas others have later onset of less severe infections. Immunologic workup usually shows normal leukocyte levels, although some patients may demonstrate alterations in lymphocyte subsets, including T cells. Affected individuals also have variable skeletal abnormalities, including high-arched palate, hyperextensible joints, scoliosis, and bone fractures. {ECO:0000269|PubMed:32207811}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hyper-IgE syndrome 4B, autosomal recessive, with recurrent infections (HIES4B) [MIM:618523]: An immunologic disorder characterized by recurrent infections, mainly affecting the respiratory tract, skin and eye, and skeletal abnormalities including craniosynostosis and scoliosis. Immunologic workup shows increased serum IgE, intermittent eosinophilia, impaired development of certain B- and T-cell populations, as well as impaired acute-phase response. Disease onset is in early childhood. {ECO:0000269|PubMed:28747427, ECO:0000269|PubMed:30309848, ECO:0000269|PubMed:33771552}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Stuve-Wiedemann syndrome 2 (STWS2) [MIM:619751]: A form of Stuve-Wiedemann syndrome, an autosomal recessive disease characterized by bowing of tubular bones and other skeletal and craniofacial abnormalities, respiratory distress, feeding difficulties, and hyperthermic episodes. Most patients do not survive past infancy. STWS2 patients manifest skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. {ECO:0000269|PubMed:31914175}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 94 with autoinflammation and dysmorphic facies (IMD94) [MIM:619750]: An autosomal dominant disorder characterized by onset in early infancy, lymphadenopathy, autoinflammation, immunodeficiency with hypogammaglobulinemia, and dysmorphic facial features. {ECO:0000269|PubMed:33517393}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Functions as a shared signal-transducing subunit not only for IL6 but also for other cytokine receptor complexes, including IL6, LIF, OSM, CNTF, IL11, CTF1, BSF3, MT-RNR2/humanin, CLCF1 and the heterodimeric complex CRLF1-CLCF1 (PubMed:11285233, PubMed:11294841, PubMed:1542794, PubMed:19386761, PubMed:2261637, PubMed:27384491, PubMed:36930708, PubMed:39532904, PubMed:8272873, PubMed:8999038, PubMed:9030543, PubMed:9188471). Engages site 2 of CNTF, CLCF1, LIF, and IL-6, and site 3 of IL27 and IL6 (PubMed:36930708). Initiates signal transmission through three mechanisms (PubMed:11285233, PubMed:11294841, PubMed:1542794, PubMed:19386761, PubMed:19915009, PubMed:2261637, PubMed:23294003). Binding of cytokines, such as IL6 or IL11 to the alpha-chains of their specific cell surface receptor triggers homodimerization of IL6ST/gp130 (PubMed:19915009, PubMed:2261637, PubMed:23294003, PubMed:8637716). In contrast, binding of other IL-6 family cytokines can result in the formation of a IL6ST/gp130 heterodimer with another signal-transducing receptor, such as LIFR or OSMR (PubMed:1542794, PubMed:39532904, PubMed:8999038, PubMed:9030543, PubMed:9188471). Moreover, binding of CNTF or CLCF1 or the heterodimeric complex CRLF1-CLCF1 or MT-RNR2/humanin to the non-signaling receptor CNTFR induces heterodimerization of the IL6ST/gp130 with LIFR or IL27RA/WSX1 (in the case of MT-RNR2/humanin) (PubMed:11285233, PubMed:11294841, PubMed:19386761). Mechanistically, homodimerization or heterodimerization of IL6ST/gp130 activate JAK tyrosine kinases bound to their intracellular domains (PubMed:11294841, PubMed:19915009, PubMed:2261637, PubMed:23294003, PubMed:27384491, PubMed:8272873, PubMed:9030543, PubMed:9188471). These kinases subsequently phosphorylate the homodimer or heterodimer form of IL6ST/gp130 (PubMed:11285233, PubMed:11294841, PubMed:19915009, PubMed:23294003, PubMed:25731159, PubMed:9030543). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducer and activators of transcription (STATs) (PubMed:11285233, PubMed:11294841, PubMed:19386761, PubMed:19915009, PubMed:23294003, PubMed:25731159, PubMed:27384491, PubMed:9030543, PubMed:9188471). The IL6 signaling pathway induces, in parallel, the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (By similarity). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (By similarity). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity). {ECO:0000250|UniProtKB:Q00560, ECO:0000269|PubMed:11285233, ECO:0000269|PubMed:11294841, ECO:0000269|PubMed:1542794, ECO:0000269|PubMed:19386761, ECO:0000269|PubMed:19915009, ECO:0000269|PubMed:2261637, ECO:0000269|PubMed:23294003, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:27384491, ECO:0000269|PubMed:28747427, ECO:0000269|PubMed:30309848, ECO:0000269|PubMed:36930708, ECO:0000269|PubMed:39532904, ECO:0000269|PubMed:8272873, ECO:0000269|PubMed:8637716, ECO:0000269|PubMed:8999038, ECO:0000269|PubMed:9030543, ECO:0000269|PubMed:9188471}.; FUNCTION: [Isoform 2]: Binds to the soluble IL6:sIL6R complex (hyper-IL6), thereby blocking IL6 trans-signaling. Inhibits sIL6R-dependent acute phase response (PubMed:11121117, PubMed:21990364, PubMed:30279168). Also blocks IL11 cluster signaling through IL11R (PubMed:30279168). {ECO:0000269|PubMed:11121117, ECO:0000269|PubMed:21990364, ECO:0000269|PubMed:30279168}.
uniprot
proteins
mass_dalton
103537
uniprot
proteins
mutagenesis
MUTAGEN 172; /note="C->S: Induces ligand-independent activation."; /evidence="ECO:0000269|PubMed:23294003"; MUTAGEN 186..190; /note="Missing: Induces ligand-independent activation."; /evidence="ECO:0000269|PubMed:23294003"; MUTAGEN 189; /note="V->G: Does not induce ligand-independent activation."; /evidence="ECO:0000269|PubMed:23294003"; MUTAGEN 190; /note="Y->G: Does not induce ligand-independent activation."; /evidence="ECO:0000269|PubMed:23294003"; MUTAGEN 215; /note="D->G: Induces ligand-independent activation."; /evidence="ECO:0000269|PubMed:23294003"; MUTAGEN 252; /note="V->G: Induces ligand-independent activation."; /evidence="ECO:0000269|PubMed:23294003"; MUTAGEN 759; /note="Y->F: Refractory to inhibition by SOCS3."; /evidence="ECO:0000269|PubMed:25731159"; MUTAGEN 782; /note="S->A: Increases cell surface expression."; /evidence="ECO:0000269|PubMed:10811661"; MUTAGEN 789..918; /note="Missing: Results in impaired cytokine-mediated signaling pathway with loss of response to IL-6 and IL-11. Weak response to IL-27, OSM and LIF."; /evidence="ECO:0000269|PubMed:32207811"; MUTAGEN 899..918; /note="Missing: Results in impaired cytokine-mediated signaling pathway with loss of response to IL-6 and IL-11. Weak response to IL-27, OSM and LIF."; /evidence="ECO:0000269|PubMed:32207811
uniprot
proteins
post_translational_modification
PTM: Phosphorylation of Ser-782 down-regulates cell surface expression. {ECO:0000269|PubMed:10811661}.; PTM: Heavily N-glycosylated (PubMed:11098061, PubMed:11251120, PubMed:16335952, PubMed:19139490, PubMed:19159218). Glycosylation is required for protein stability and localization in plasma membrane but not for ligand binding (PubMed:19915009). {ECO:0000269|PubMed:11098061, ECO:0000269|PubMed:11251120, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19915009}.
uniprot
proteins
protein_family
Type 2 subfamily
uniprot
proteins
protein_family
Type I cytokine receptor family
uniprot
proteins
pubmed
10811661
uniprot
proteins
pubmed
10880057
uniprot
proteins
pubmed
11098061
uniprot
proteins
pubmed
11121117
uniprot
proteins
pubmed
11238858
uniprot
proteins
pubmed
11251120
uniprot
proteins
pubmed
11285233
uniprot
proteins
pubmed
11294841
uniprot
proteins
pubmed
12829785
uniprot
proteins
pubmed
14527405
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
1542794
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19139490
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19386761
uniprot
proteins
pubmed
19915009
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20489211
uniprot
proteins
pubmed
21990364
uniprot
proteins
pubmed
2261637
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23294003
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24629561
uniprot
proteins
pubmed
25242236
uniprot
proteins
pubmed
25731159
uniprot
proteins
pubmed
26876177
uniprot
proteins
pubmed
26927669
uniprot
proteins
pubmed
27384491
uniprot
proteins
pubmed
28747427
uniprot
proteins
pubmed
30279168
uniprot
proteins
pubmed
30309848
uniprot
proteins
pubmed
31914175
uniprot
proteins
pubmed
32207811
uniprot
proteins
pubmed
33517393
uniprot
proteins
pubmed
33771552
uniprot
proteins
pubmed
36930708
uniprot
proteins
pubmed
39532904
uniprot
proteins
pubmed
8272873
uniprot
proteins
pubmed
8637716
uniprot
proteins
pubmed
8999038
uniprot
proteins
pubmed
9030543
uniprot
proteins
pubmed
9188471
uniprot
proteins
pubmed
9406996
uniprot
proteins
pubmed
9501088
uniprot
proteins
sequence_length
918
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:19915009}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000269|PubMed:24629561}.
uniprot
proteins
transmembrane_region
TRANSMEM 620..641; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins