Overview
| Uniprot ID | P40189 |
|---|
| Protein Name | Interleukin-6 receptor subunit beta |
|---|
| Gene Name | IL6ST |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 374 |
EVTLTRWKSHLQNYT |
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)
Protein Sequence
10
MLTLQTWLVQ
20
ALFIFLTTES
30
TGELLDPCGY
40
ISPESPVVQL
50
HSNFTAVCVL
60
KEKCMDYFHV
70
NANYIVWKTN
80
HFTIPKEQYT
90
IINRTASSVT
100
FTDIASLNIQ
110
LTCNILTFGQ
120
LEQNVYGITI
130
ISGLPPEKPK
140
NLSCIVNEGK
150
KMRCEWDGGR
160
ETHLETNFTL
170
KSEWATHKFA
180
DCKAKRDTPT
190
SCTVDYSTVY
200
FVNIEVWVEA
210
ENALGKVTSD
220
HINFDPVYKV
230
KPNPPHNLSV
240
INSEELSSIL
250
KLTWTNPSIK
260
SVIILKYNIQ
270
YRTKDASTWS
280
QIPPEDTAST
290
RSSFTVQDLK
300
PFTEYVFRIR
310
CMKEDGKGYW
320
SDWSEEASGI
330
TYEDRPSKAP
340
SFWYKIDPSH
350
TQGYRTVQLV
360
WKTLPPFEAN
370
GKILDYEVTL
380
TRWKSHLQNY
390
TVNATKLTVN
400
LTNDRYLATL
410
TVRNLVGKSD
420
AAVLTIPACD
430
FQATHPVMDL
440
KAFPKDNMLW
450
VEWTTPRESV
460
KKYILEWCVL
470
SDKAPCITDW
480
QQEDGTVHRT
490
YLRGNLAESK
500
CYLITVTPVY
510
ADGPGSPESI
520
KAYLKQAPPS
530
KGPTVRTKKV
540
GKNEAVLEWD
550
QLPVDVQNGF
560
IRNYTIFYRT
570
IIGNETAVNV
580
DSSHTEYTLS
590
SLTSDTLYMV
600
RMAAYTDEGG
610
KDGPEFTFTT
620
PKFAQGEIEA
630
IVVPVCLAFL
640
LTTLLGVLFC
650
FNKRDLIKKH
660
IWPNVPDPSK
670
SHIAQWSPHT
680
PPRHNFNSKD
690
QMYSDGNFTD
700
VSVVEIEAND
710
KKPFPEDLKS
720
LDLFKKEKIN
730
TEGHSSGIGG
740
SSCMSSSRPS
750
ISSSDENESS
760
QNTSSTVQYS
770
TVVHSGYRHQ
780
VPSVQVFSRS
790
ESTQPLLDSE
800
ERPEDLQLVD
810
HVDGGDGILP
820
RQQYFKQNCS
830
QHESSPDISH
840
FERSKQVSSV
850
NEEDFVRLKQ
860
QISDHISQSC
870
GSGQMKMFQE
880
VSAADAFGPG
890
TEGQVERFET
900
VGMEAATDEG
910
MPKSYLPQTV
RQGGYMPQ
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0070110 |
ciliary neurotrophic factor receptor complex |
| Cellular Component |
GO:0030425 |
dendrite |
| Cellular Component |
GO:0009897 |
external side of plasma membrane |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0005576 |
extracellular region |
| Cellular Component |
GO:0005615 |
extracellular space |
| Cellular Component |
GO:0005896 |
interleukin-6 receptor complex |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0045121 |
membrane raft |
| Cellular Component |
GO:0043025 |
neuronal cell body |
| Cellular Component |
GO:0005900 |
oncostatin-M receptor complex |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0043235 |
receptor complex |
| Molecular Function |
GO:0004897 |
ciliary neurotrophic factor receptor activity |
| Molecular Function |
GO:0005127 |
ciliary neurotrophic factor receptor binding |
| Molecular Function |
GO:0015026 |
coreceptor activity |
| Molecular Function |
GO:0019955 |
cytokine binding |
| Molecular Function |
GO:0004896 |
cytokine receptor activity |
| Molecular Function |
GO:0019838 |
growth factor binding |
| Molecular Function |
GO:0042802 |
identical protein binding |
| Molecular Function |
GO:0019970 |
interleukin-11 binding |
| Molecular Function |
GO:0004921 |
interleukin-11 receptor activity |
| Molecular Function |
GO:0045509 |
interleukin-27 receptor activity |
| Molecular Function |
GO:0030296 |
protein tyrosine kinase activator activity |
| Molecular Function |
GO:0097110 |
scaffold protein binding |
| Biological Process |
GO:0035425 |
autocrine signaling |
| Biological Process |
GO:0030183 |
B cell differentiation |
| Biological Process |
GO:0007259 |
cell surface receptor signaling pathway via JAK-STAT |
| Biological Process |
GO:0097696 |
cell surface receptor signaling pathway via STAT |
| Biological Process |
GO:0070120 |
ciliary neurotrophic factor-mediated signaling pathway |
| Biological Process |
GO:0019221 |
cytokine-mediated signaling pathway |
| Biological Process |
GO:0006954 |
inflammatory response |
| Biological Process |
GO:0038154 |
interleukin-11-mediated signaling pathway |
| Biological Process |
GO:0070106 |
interleukin-27-mediated signaling pathway |
| Biological Process |
GO:0070102 |
interleukin-6-mediated signaling pathway |
| Biological Process |
GO:0060576 |
intestinal epithelial cell development |
| Biological Process |
GO:0048861 |
leukemia inhibitory factor signaling pathway |
| Biological Process |
GO:0030219 |
megakaryocyte differentiation |
| Biological Process |
GO:0043066 |
negative regulation of apoptotic process |
| Biological Process |
GO:0060302 |
negative regulation of cytokine activity |
| Biological Process |
GO:0001960 |
negative regulation of cytokine-mediated signaling pathway |
| Biological Process |
GO:0070345 |
negative regulation of fat cell proliferation |
| Biological Process |
GO:0070104 |
negative regulation of interleukin-6-mediated signaling pathway |
| Biological Process |
GO:0043524 |
negative regulation of neuron apoptotic process |
| Biological Process |
GO:0002826 |
negative regulation of T-helper 1 type immune response |
| Biological Process |
GO:0038165 |
oncostatin-M-mediated signaling pathway |
| Biological Process |
GO:0038001 |
paracrine signaling |
| Biological Process |
GO:0002675 |
positive regulation of acute inflammatory response |
| Biological Process |
GO:0002821 |
positive regulation of adaptive immune response |
| Biological Process |
GO:0010613 |
positive regulation of cardiac muscle hypertrophy |
| Biological Process |
GO:0008284 |
positive regulation of cell population proliferation |
| Biological Process |
GO:0032733 |
positive regulation of interleukin-10 production |
| Biological Process |
GO:0043410 |
positive regulation of MAPK cascade |
| Biological Process |
GO:0045747 |
positive regulation of Notch signaling pathway |
| Biological Process |
GO:0045669 |
positive regulation of osteoblast differentiation |
| Biological Process |
GO:1901731 |
positive regulation of platelet aggregation |
| Biological Process |
GO:0042102 |
positive regulation of T cell proliferation |
| Biological Process |
GO:0010575 |
positive regulation of vascular endothelial growth factor production |
| Biological Process |
GO:0050796 |
regulation of insulin secretion |
| Biological Process |
GO:0034097 |
response to cytokine |
| Biological Process |
GO:0072540 |
T-helper 17 cell lineage commitment |
Reference
PMID: N/A