IL6ST

Protein identityUniProt · HPA

UniProt accession

P40189

Gene

IL6ST

Ensembl

ENSG00000134352

Chromosome

5

Canonical length

918 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, CD markers, Disease related genes, Human disease related genes, Plasma proteins, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Golgi apparatus,Plasma membrane

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a signal transducer shared by many cytokines, including interleukin 6 (IL6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M (OSM). This protein functions as a part of the cytokine receptor complex. The activation of this protein is dependent upon the binding of cytokines to their receptors. vIL6, a protein related to IL6 and encoded by the Kaposi sarcoma-associated herpesvirus, can bypass the interleukin 6 receptor (IL6R) and directly activate this protein. Knockout studies in mice suggest that this gene plays a critical role in regulating myocyte apoptosis. Alternatively spliced transcript variants have been described. A related pseudogene has been identified on chromosome 17. [provided by RefSeq, May 2014]

Canonical amino-acid sequenceUniProt

918 residues, UniProt reviewed canonical sequence.

>P40189|IL6ST
     1  MLTLQTWLVQ ALFIFLTTES TGELLDPCGY ISPESPVVQL HSNFTAVCVL KEKCMDYFHV
    61  NANYIVWKTN HFTIPKEQYT IINRTASSVT FTDIASLNIQ LTCNILTFGQ LEQNVYGITI
   121  ISGLPPEKPK NLSCIVNEGK KMRCEWDGGR ETHLETNFTL KSEWATHKFA DCKAKRDTPT
   181  SCTVDYSTVY FVNIEVWVEA ENALGKVTSD HINFDPVYKV KPNPPHNLSV INSEELSSIL
   241  KLTWTNPSIK SVIILKYNIQ YRTKDASTWS QIPPEDTAST RSSFTVQDLK PFTEYVFRIR
   301  CMKEDGKGYW SDWSEEASGI TYEDRPSKAP SFWYKIDPSH TQGYRTVQLV WKTLPPFEAN
   361  GKILDYEVTL TRWKSHLQNY TVNATKLTVN LTNDRYLATL TVRNLVGKSD AAVLTIPACD
   421  FQATHPVMDL KAFPKDNMLW VEWTTPRESV KKYILEWCVL SDKAPCITDW QQEDGTVHRT
   481  YLRGNLAESK CYLITVTPVY ADGPGSPESI KAYLKQAPPS KGPTVRTKKV GKNEAVLEWD
   541  QLPVDVQNGF IRNYTIFYRT IIGNETAVNV DSSHTEYTLS SLTSDTLYMV RMAAYTDEGG
   601  KDGPEFTFTT PKFAQGEIEA IVVPVCLAFL LTTLLGVLFC FNKRDLIKKH IWPNVPDPSK
   661  SHIAQWSPHT PPRHNFNSKD QMYSDGNFTD VSVVEIEAND KKPFPEDLKS LDLFKKEKIN
   721  TEGHSSGIGG SSCMSSSRPS ISSSDENESS QNTSSTVQYS TVVHSGYRHQ VPSVQVFSRS
   781  ESTQPLLDSE ERPEDLQLVD HVDGGDGILP RQQYFKQNCS QHESSPDISH FERSKQVSSV
   841  NEEDFVRLKQ QISDHISQSC GSGQMKMFQE VSAADAFGPG TEGQVERFET VGMEAATDEG
   901  MPKSYLPQTV RQGGYMPQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IL6ST can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

182 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IL6ST.

Disease | AllUniProt

Conditions IL6ST is implicated in, by any mechanism.

• Hyper-IgE syndrome 4A, autosomal dominant, with recurrent infections (HIES4A) MIM:619752
• Hyper-IgE syndrome 4B, autosomal recessive, with recurrent infections (HIES4B) MIM:618523
• Stuve-Wiedemann syndrome 2 (STWS2) MIM:619751
• Immunodeficiency 94 with autoinflammation and dysmorphic facies (IMD94) MIM:619750

Disease | GeneticClinVar

24 pathogenic / likely-pathogenic of 647 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hyper-IgE recurrent infection syndrome 4A, autosomal dominant
• Stuve-Wiedemann syndrome 2
• Hyper-IgE recurrent infection syndrome 4, autosomal recessive
• Stuve-Wiedemann syndrome
• Immunodeficiency 94 with autoinflammation and dysmorphic facies

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.23

gnomAD pLI

1

gnomAD missense Z

1.06

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell surface receptor signaling pathway via STAT
• ciliary neurotrophic factor-mediated signaling pathway
• cytokine-mediated signaling pathway
• glycogen metabolic process
• interleukin-11-mediated signaling pathway
• interleukin-27-mediated signaling pathway
• interleukin-6-mediated signaling pathway
• intestinal epithelial cell development
• leukemia inhibitory factor signaling pathway
• negative regulation of apoptotic process
• negative regulation of interleukin-6-mediated signaling pathway
• negative regulation of neuron apoptotic process
• oncostatin-M-mediated signaling pathway
• positive regulation of acute inflammatory response
• positive regulation of adaptive immune response
• positive regulation of astrocyte differentiation
• positive regulation of cardiac muscle hypertrophy
• positive regulation of cell population proliferation
• positive regulation of Notch signaling pathway
• positive regulation of osteoblast differentiation
• positive regulation of platelet aggregation
• positive regulation of T cell proliferation
• positive regulation of vascular endothelial growth factor production
• response to cytokine
• T-helper 17 cell lineage commitment

Molecular functions

• ciliary neurotrophic factor receptor activity
• ciliary neurotrophic factor receptor binding
• coreceptor activity
• cytokine binding
• cytokine receptor activity
• growth factor binding
• identical protein binding
• interleukin-11 binding
• interleukin-11 receptor activity
• interleukin-27 receptor activity
• interleukin-6 receptor activity
• protein tyrosine kinase activator activity
• scaffold protein binding

Cellular components

• ciliary neurotrophic factor receptor complex
• dendrite
• external side of plasma membrane
• extracellular exosome
• extracellular region
• extracellular space
• interleukin-6 receptor complex
• membrane
• membrane raft
• neuronal cell body
• oncostatin-M receptor complex
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Long hematopoietin receptor, Gp130 family 2, conserved site
• Fibronectin type III
• Immunoglobulin C2-set-like, ligand-binding
• Immunoglobulin-like fold
• Fibronectin type III superfamily
• Type I Cytokine Receptor
• Fibronectin type III domain
• Ig-like C2-type domain
• Leukemia inhibitory factor receptor D4 domain

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• Host-virus interaction
• Immunoglobulin domain
• Membrane
• Phosphoprotein
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of IL6ST in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARMH4
• HCK
• SRC
• YES