Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001423
UniProt IDP40189
Primary gene name(s)IL6ST
Synonym gene name(s)unknown
Protein nameInterleukin-6 receptor subunit beta
Protein functionSignal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates Janus kinases, PubMed:2261637. That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3, PubMed:19915009, PubMed:23294003. Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism, By similarity. Has a role in embryonic development, By similarity. Does not bind IL6, PubMed:2261637. 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:19915009, ECO:0000269|PubMed:2261637, ECO:0000269|PubMed:23294003}.
Subcellular locationIsoform 1: Cell membrane {ECO:0000269|PubMed:19915009};
Single-pass type I membrane protein {ECO:0000255}.;
SUBCELLULAR LOCATION: Isoform 2: Secreted {ECO:0000269|PubMed:24629561}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P40189
Gene Ontology
(Biological Process)
Complete annatation
ciliary neurotrophic factor-mediated signaling pathway [GO:0070120];
cytokine-mediated signaling pathway [GO:0019221];
glycogen metabolic process [GO:0005977];
interleukin-27-mediated signaling pathway [GO:0070106];
interleukin-6-mediated signaling pathway [GO:0070102];
leukemia inhibitory factor signaling pathway [GO:0048861];
negative regulation of apoptotic process [GO:0043066];
negative regulation of interleukin-6-mediated signaling pathway [GO:0070104];
oncostatin-M-mediated signaling pathway [GO:0038165];
positive regulation of acute inflammatory response [GO:0002675];
positive regulation of adaptive immune response [GO:0002821];
positive regulation of astrocyte differentiation [GO:0048711];
positive regulation of cardiac muscle hypertrophy [GO:0010613];
positive regulation of cell proliferation [GO:0008284];
positive regulation of osteoblast differentiation [GO:0045669];
positive regulation of T cell proliferation [GO:0042102];
positive regulation of tyrosine phosphorylation of Stat1 protein [GO:0042511];
positive regulation of tyrosine phosphorylation of Stat3 protein [GO:0042517];
positive regulation of vascular endothelial growth factor production [GO:0010575];
regulation of Notch signaling pathway [GO:0008593];
response to cytokine [GO:0034097];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
ciliary neurotrophic factor receptor activity [GO:0004897];
ciliary neurotrophic factor receptor binding [GO:0005127];
growth factor binding [GO:0019838];
interleukin-11 receptor activity [GO:0004921];
interleukin-27 receptor activity [GO:0045509];
protein homodimerization activity [GO:0042803]
Gene Ontology
(Cellular Component)
Complete annatation
ciliary neurotrophic factor receptor complex [GO:0070110];
dendrite [GO:0030425];
external side of plasma membrane [GO:0009897];
extracellular exosome [GO:0070062];
extracellular region [GO:0005576];
extracellular space [GO:0005615];
interleukin-6 receptor complex [GO:0005896];
membrane [GO:0016020];
neuronal cell body [GO:0043025];
oncostatin-M receptor complex [GO:0005900];
plasma membrane [GO:0005886]
Protein-protein interaction109786
Phylogenetic treeP40189
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.7060777328514360.03699485311188880.0776150370409782
AZA vs. DISU0.4863582941831020.2376705405584550.821854758571361
AZA vs. IL7-0.2292283118862670.5435456979039210.999311006273513
AZA vs. SAHA0.6691345336407170.08499352836850240.364700383326731
DISU vs. CD3-0.2333965965985070.5243524914211870.64591725551058
DISU vs. IL7-0.7232294179273630.06100094150386050.326326896086124
DISU vs. SAHA0.1815827005503460.6504992283612970.891919383390081
DMSO vs. AZA-0.1372630261254650.6849581247373461
DMSO vs. CD3-0.8608795943491160.007477112647533260.0193977444524003
DMSO vs. DISU-0.6272474475164490.0703999784738560.495992368209916
DMSO vs. IL7-0.08396490532049130.783397310160120.955401217592736
DMSO vs. SAHA0.7983323664287960.01260128502532820.104813494742731
HIV vs. Mock in Activation-0.354512203841390.573638762064320.999983755607037
HIV vs. Mock in Latency-0.3112831292027340.05978314817171640.956657298875215
IL7 vs. CD3-0.9233638666038980.004448838312990260.0151954089942674
SAHA vs. CD3-0.06549132336480080.8527049774249650.895551188918685
SAHA vs. IL70.8912826244439040.014436041120790.0808502324033597
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
0.6712 0.01539

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.782664 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
212195_at 1.83 No downregulated in CD8+ cells
212196_at 1.71 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1BJ8 NMR - A=219-325.
1BQU X-ray 2.0Å A/B=122-333.
1I1R X-ray 2.4Å A=23-325.
1N2Q Model - A/B=23-324.
1P9M X-ray 3.6Å A=23-321.
1PVH X-ray 2.5Å A/C=123-323.
3L5H X-ray 3.6Å A=24-612.
3L5I X-ray 1.9Å A=323-612.
3L5J X-ray 3.0Å A/B=323-610.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Nef downregulates 25275127
Tat upregulates 15857508
HIV-1 virus replication enhanced by expression of human gene 19460752

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04630 Jak-STAT signaling pathway - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)