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FLASH GENE
Symbol CSF1R contributors: mct/npt/pgu - updated : 14-09-2015
HGNC name colony stimulating factor 1 receptor
HGNC id 2433
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a highly glycosylated extracellular ligand-binding domain
  • a transmembrane domain
  • an intracellular tyrosine kinase domain
  • HOMOLOGY
    interspecies homolog to feline McDonough sarcoma viral,oncogene (v-fms)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • CSF-1/PDGF receptor subfamily
  • CATEGORY enzyme , signaling cytokine , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • ligand activated protein-tyrosine kinase that utilizes autophosphorylation sites to regulate kinase activity and to control interactions with signaling proteins
  • disrupts cell adhesion by uncoupling adherens junction complexes from the cytoskeleton and promoting cadherin internalization through a Src-dependent mechanism and could contribute to invasive progression in epithelial cancers
  • undergoes regulated intramembrane proteolysis, releasing the intracellular domain from the plasma membrane, enabling it to move to other compartments within the cell to participate in signaling
  • tyrosine kinase receptor that is absolutely required for macrophage differentiation and thus occupies a central role in hematopoiesis
  • CSF1R, through GAB2, utilizes different effectors at different stages of mononuclear phagocytes development to promote their expansion
  • required for the development of microglia, for a fully functional olfactory system and the maintenance of normal brain structure
  • presence of functional nucleus-associated CSF1Rs, which are activated by extracellular CSF1 by a mechanism that involves PIK3CA and RAB5 activity
  • is a crucial mediator of microglial proliferation and differentiation in the brain
  • directly regulates the development of Paneth cells (PC) and influences proliferation and cell fate in the small intestine
  • CSF1R signaling plays potentially an important role in colon homeostasis and stem cell gene expression
  • CSF1R was involved in the maintenance of adult microglia and the receptor for the cytokine TGFB1 suppressed activation of microglia
  • plays key roles in regulating development and function of the monocyte/macrophage lineage, including microglia and osteoclasts
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with HCK (dysregulated activation of HCK at the Golgi disturbs N-glycosylation of CSF1R)
  • IL34 is a ligand of CSF1R
  • GAB2 is a major tyrosyl phosphoprotein in the CSF1R signaling network
  • PSTPIP2 acts as a negative feedback regulator of CSF1R signaling to suppress inflammation and osteoclastogenesis
  • activation of the MAPK7/MAP2K5 pathway with CSF1R is required for osteoclast differentiation, which may induce differentiation through the induction of FOS
  • cell & other
    REGULATION
    activated by toll-like receptors (stimulate regulated intramembrane proteolysis of the CSF1R through Erk activation)
    ASSOCIATED DISORDERS
    corresponding disease(s) HDLS , DOSBF
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    deregulated in anaplastic large cell lymphoma (ALCL) with and without the characteristic t(2;5)(p23;q35)
    tumoral fusion      
    with RBM6 in a t(3;5)(p21;q33) in megakaryoblastic leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • brain abnormalities of Csf1r-/- mice are characterized by severe microglial depletion and enlarged ventricles, probably attributing to the early lethality