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FLASH GENE
Symbol CISH contributors: mct - updated : 28-05-2020
HGNC name cytokine inducible SH2-containing protein
HGNC id 1984
Location 3p21.2      Physical location : 50.643.885 - 50.649.262
Synonym name
  • cytokine-inducible inhibitor of signaling type 1B
  • suppressor of cytokine signaling
  • protein G18
  • Synonym symbol(s) CIS, CIS-1, G18, SOCS, BACTS2
    DNA
    TYPE functioning gene
    STRUCTURE 5.38 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 2192 28.7 258 - 2019 30197185
  • also called CIS1
  • distinct 5' utr
  • 4 initiation site 2285 - 275 placenta 2019 30197185
  • also called CIS1B
  • distinct 5' utr
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Reproductivefemale systembreastmammary gland  
     female systemplacenta  highly
     female systemovary  highly
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text predominantly in kidney
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • Src solitary SH2 homology domain followed by a C terminal
  • a SOCS box domain
  • HOMOLOGY
    interspecies homolog to murine Cish
    Homologene
    FAMILY suppressor of cytokine signaling (SOCS) family
    CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    text localization regulated by cellular conditions (nuclear localization being stimulated by conditions that increased cytoplasmic protein levels)
    basic FUNCTION
  • negative regulator of the JAK STAT signaling pathway
  • negatively regulates cytokine signaling by inhibiting JAK2/STAT5 activity
  • plays a crucial role in type 1 dendritic cell (DC) development as well as in the DC-mediated activation of cytotoxic T lymphocytes (CTLs)
  • CISH plays a key role in the eosinophilic inflammation associated with bronchial asthma by regulating IL13-induced CCL26 production
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • leading EPOR to proteasome mediated degradation
  • interacting with SOCS3
  • ELOB/ELOC recruitment regulates substrate binding by CISH
  • NR1H4-mediated upregulation of CISH may play an important role in the homeostasis of cytokine signal networks and be beneficial to control cytokine-associated inflammatory diseases
  • CISH inhibits prolactin receptor (PRLR) signaling and acts as part of an E3 ubiquitin ligase complex through interactions with ELOB/ELOC proteins
  • CISH physically interacts with the TCR intermediate PLCG1, targeting it for proteasomal degradation after TCR stimulation
  • is a critical negative regulator of IL15 signaling in NK cells (
  • CISH interacted with the tyrosine kinase JAK1, inhibiting its enzymatic activity and targeting JAK for proteasomal degradation (
  • cell & other
    REGULATION
    induced by induced by IL2, IL3, EPO
    TCR stimulation in CD8(+) T cells
    Other CISH protein stability is regulated through multiple mechanisms, including ubiquitination and interaction with ELOB/ELOC proteins, whereas CISH functional inhibition of PRLR signaling is dependent on the ELOB/ELOC interaction
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Cish(-/-) mice were resistant to melanoma, prostate and breast cancer metastasis in vivo, and this was intrinsic to NK cell activity