Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SOCS6 contributors: mct - updated : 08-02-2016
HGNC name suppressor of cytokine signaling 6
HGNC id 16833
Location 18q22.2      Physical location : 67.956.136 - 67.997.434
Synonym name
  • STAT induced STAT inhibitory 4
  • cytokine inducible SH2 protein 4
  • suppressor of cytokine signaling 4
  • Synonym symbol(s) CIS4, SSI4, STAI4, STAT4, STATI4, HSPC060, SOCS4, CISH4
    DNA
    TYPE functioning gene
    STRUCTURE 41.30 kb     2 Exon(s)
    regulatory sequence Binding site   transcription factor
    text structure major transcription initiation site is located 469 bp upstream the ATG codon
  • 5prime-flanking region is able to drive transcription, and the CpG-rich sequences near the transcription initiation site are important for the TATA-less SOCS6 promoter activity
  • consensus binding sequences for several transcription factors including AP1, AP2, AP4, BRE, C/EBP, CREB, E2F, GATA-1, OCT1, p53, SP1, NFAT, c-Myb, MZF
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text two SOCS6 transcripts were generated from the major transcription initiation site due to the usage of the two alternative polyadenylation sites (PMID: 19716864)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 5846 59.5 535 - 2009 19716864
    - - 2919 59.5 535 - 2009 19716864
    EXPRESSION
    Rna function skeletal muscle, placenta, tongue
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestivesalivary gland   highly
     stomach   moderately
    Endocrineparathyroid   highly
     thyroid   moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic
    Skin/Tegumentmelanocyte
    cell lineage
    cell lines factor independent CML, erythroleukemia
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text umbilical cord, embryonic tissue
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal amino acids 1-210 sufficient to locate the protein into the nucleus solitary in both the cytoplasm and the nucleus, and the KID domain (AA 47218) provides an interface for binding the kinase domain of LCK
  • a central Src homology SH2 domain
  • at least two functional domains required for its biological role in localizing and degrading STAT3 in the nucleus
  • a C terminal conserved SOCS box, acting as a common binding domain for a large family of E3 ubiquitin protein ligases
  • an SH2 domain, in the cytoplasm
  • HOMOLOGY
    interspecies homolog to rattus Socs6 (84.91 pc)
    homolog to murine Socs6 (85.66 pc)
    Homologene
    FAMILY
  • SOCS protein family
  • CIS family
  • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • primarily located and regulated in the cytoplasm, and in the nucleus
  • localizes to the nucleus where it reduces STAT3
  • basic FUNCTION
  • part of a classical negative feedback system that regulates cytokine signal transduction
  • having a putative function as a negative regulator of receptor tyrosine kinases
  • having at least two functional domains required for its biological role in localizing and degrading STAT3 in the nucleus
  • negative regulator of cytokine signaling pathways
  • negative regulator of LCK
  • in response to TCR stimulation, associates with and negatively regulates LCK
  • important role for SOCS6 in cellular homeostasis
  • acting as a negative regulator of T cell activation by promoting ubiquitin-dependent proteolysis
  • CELLULAR PROCESS nucleotide, transcription, regulation
    protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to elongin B and C through its SOCS box
  • interacting with IRS4 and IRS2
  • binds to KIT juxtamembrane region, which affects upstream signaling components leading to MAPK activation
  • interacts with RBCK1, a type of E3 ubiquitin ligase involved in proteasome-mediated degradation
  • targeting LCK to proteasome-dependent degradation in response to T cell activation and negative regulation of LCK by SOCS6 may in part prevent uncontrolled T cell activation
  • SOCS6 negatively regulates FLT3 activation, the downstream Erk signaling pathway, and cell proliferation
  • cell & other
    REGULATION
    induced by induced by erythropoietin (EPO) and granulocyte macrophage CSF (CSF2) in hematopoietic cell lines
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    frequent event in gastric tumorigenesis
    tumoral     --low  
    in carcinomas of stomach and colon
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS