Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008383
UniProt IDO14543
Primary gene name(s)SOCS3
Synonym gene name(s)CIS3, SSI3
Protein nameSuppressor of cytokine signaling 3
Protein functionSOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo, By similarity. Probable substrate recognition component of a SCF-like ECS, Elongin BC-CUL2/5-SOCS-box protein E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Seems to recognize IL6ST, By similarity. {ECO:0000250, ECO:0000269|PubMed:15601820}.
Subcellular locationunknown
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O14543
Gene Ontology
(Biological Process)
Complete annatation
branching involved in labyrinthine layer morphogenesis [GO:0060670];
cytokine-mediated signaling pathway [GO:0019221];
JAK-STAT cascade [GO:0007259];
negative regulation of apoptotic process [GO:0043066];
negative regulation of inflammatory response [GO:0050728];
negative regulation of insulin receptor signaling pathway [GO:0046627];
negative regulation of JAK-STAT cascade [GO:0046426];
negative regulation of tyrosine phosphorylation of Stat1 protein [GO:0042512];
negative regulation of tyrosine phosphorylation of Stat3 protein [GO:0042518];
placenta blood vessel development [GO:0060674];
positive regulation of cell differentiation [GO:0045597];
positive regulation of tyrosine phosphorylation of Stat3 protein [GO:0042517];
protein ubiquitination [GO:0016567];
regulation of growth [GO:0040008];
regulation of interferon-gamma-mediated signaling pathway [GO:0060334];
spongiotrophoblast differentiation [GO:0060708];
trophoblast giant cell differentiation [GO:0060707]
Gene Ontology
(Molecular Function)
Complete annatation
protein kinase inhibitor activity [GO:0004860]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829]
Protein-protein interaction114488
Phylogenetic treeO14543
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. CD31.234214149408710.0002225929528382190.000974135013117779
AZA vs. DISU-0.1622756331526440.5305279271114310.940949166421897
AZA vs. IL70.8249444646414383.37834091775902e-050.00735853479400084
AZA vs. SAHA0.2181624134203810.3834928344063790.747090090459127
DISU vs. CD3-1.409226708952640.0001456173015008670.000786750968754145
DISU vs. IL70.9785923385251750.0001500739827698940.00715938382992452
DISU vs. SAHA0.3817120343425390.1974444946893940.568564350107856
DMSO vs. AZA0.03328986005158440.8503006749194481
DMSO vs. CD3-1.219138116510830.0001856541085372140.000777991417277645
DMSO vs. DISU0.191733640626880.4421673155857730.88481226104637
DMSO vs. IL70.799947541674432.98368801536775e-050.00483646202491062
DMSO vs. SAHA0.1796681020928140.4572950141841570.7868356157974
HIV vs. Mock in Activation0.0120577688569070.9846184969316170.999983755607037
HIV vs. Mock in Latency-0.7488823497986840.006706080597407630.248983888978627
IL7 vs. CD3-0.4004165925607050.2152763735792010.341041498275119
SAHA vs. CD3-1.041651462537250.003758001806368760.0111526363178372
SAHA vs. IL7-0.6104700146062070.0142597244917870.0800562707594777
(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
unknown unknown

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) unknown
(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 0.839007 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
206360_s_at 1.6 No downregulated in CD8+ cells
206359_at 1.62 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

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

HIV Partner Interaction Type PubMed
Tat upregulates 20631305
Tat downregulates 22632162
Envelope surface glycoprotein gp120 recruits 23554973

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04630 Jak-STAT signaling pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04930 Type II diabetes mellitus - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)