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FLASH GENE
Symbol SOCS1 contributors: mct/pgu - updated : 11-07-2017
HGNC name suppressor of cytokine signaling 1
HGNC id 19383
Location 16p13.13      Physical location : 11.348.273 - 11.350.039
Synonym name
  • JAK binding protein
  • TEC interacting protein 3
  • STAT induced SH3 protein 1
    • Synonym symbol(s) SSI1, JAB, TIP3, CIS1, CISH1, SOCS-1
    DNA
    TYPE functioning gene
    STRUCTURE 1.00 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   silencer
    text structure
  • JAK2
    • MAPPING cloned Y linked N status confirmed
    Map pter - D16S497 - SOCS1 - D16S414 - cen
    RNA
    TRANSCRIPTS type messenger
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinesmall intestine  highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemovary  highly
    Respiratorylung    
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • solitary central Src homology SH2 domain
  • a C terminal SOCS, CIS (CH domain) sequence, including a BC (elongin B, C binding) box
    • HOMOLOGY
    interspecies ortholog to murine Cish1
    Homologene
    FAMILY SOCS family or STAT-induced STAT inhibitor family
    CATEGORY adaptor , regulatory , tumor suppressor , signaling cytokine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    intracellular,nuclear envelope,matrix attachement regions
    text
  • attached to the somatic nuclear matrix through a matrix attachment region (MAR)
  • localization regulated by cellular conditions (nuclear localization being stimulated by conditions that increased cytoplasmic protein levels)
    • basic FUNCTION
  • involved in the interleukin-6 induced receptor phosphorylation and in the negative regulation of cytokine induced JAK/ STAT pathway
  • functioning downstream of cytokine receptors
  • taking part in a negative feedback loop to alternate cytokine signaling
  • negative regulator of IFN-gamma signaling
  • adaptor protein in receptor tyrosine kinase signaling pathways, modulating innate immunity
  • negative regulator of prolactin signaling and of LPS-induced macrophage activation
  • inhibiting the IFNG inflammatory response when overexpressed in keratinocytes
  • acting as negative regulator in insulin signaling and serving as one of the missing links between insulin resistance and cytokine signaling
  • may be involved in over-production of collagen from lung fibroblasts
  • having an important role in the negative regulation of both the JAK-STAT signalling cascade and the TLR pathway during the development of inflammatory bowel diseases
  • important role for host defence against viral infections through the regulation of the sensitivity of tissue cells to IFN
  • may play an important role in sepsis
  • promotes myogenic differentiation by specifically inhibiting the JAK1/STAT1/STAT3 pathway
  • SOCS1 and SOCS3 are induced upon TCR stimulation, and would play a role in activation-induced cell death by sensitizing activated T cells toward Fas-mediated apoptosis to maintain T cell homeostasis
    • CELLULAR PROCESS cell life, cell death/apoptosis
    protein, degradation
    PHYSIOLOGICAL PROCESS inflammation
    text
  • supressor of TNF cell death in fibroblasts
    • PATHWAY
    metabolism
    signaling signal transduction
    inhibitor of JAK signaling pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with the VHL/elongin B, C /CUL2/UBE2*(VCB-CUL2 complex)
  • JAK2
  • binds to the domain in the catalytic loop essential for IRS2 recognition
  • interacting with PIM1 (modulates its stability and functions)
  • binding and inhibiting JAK1
  • SOCS1 and SOCS3 exhibit enhanced adhesion and reduced migration towards the chemokine CCL11
  • interacts with oncogenic lymphocyte-specific protein tyrosine kinase (LCK)
  • ZBTB17 can bind to the SOCS1 promoter, suggesting that ZBTB17 deficiency causes a deregulation of SOCS1
  • SOCS1 negatively regulates IFNG1 signaling pathway (and other pathways) by directly inhibiting JAK1, JAK2
    • cell & other
    REGULATION
    induced by stress
    a subset of cytokines (including IL2,IL3,erythropoietin (EPO),CSF2/GM-CSF and interferon (IFN)-gamma
    NDRG2 expression
    repressed by GFI1B (for controlling cytokine responsiveness )
    Other differentially regulated in villous placenta in the onset of the labor
    tyrosine phosphorylated in response to M-CSF
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    silenced by methylation in hepatocellular carcinoma (loss of function) and pancreatic cancer
    tumoral   LOH    
    in newly diagnosed acute myeloid leukemia in progression
    constitutional     --low  
    in idiopathic pulmonary fibrosis (IPF), resulted in increased collagen and parenchymal fibrosis production
    tumoral     --over  
    significantly associated with earlier tumour stage and better clinical outcome in human breast cancer
    constitutional     --low  
    significantly down-regulated in multiple sclerosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • strong associations between APC, GSTP1 and SOCS1 gene promoter methylation and the risk of HCC, suggesting these to be promising biomarkers for hepatocellular carcinoma (HCC)
    • Therapy target
    ANIMAL & CELL MODELS
    knockout mice