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FLASH GENE
Symbol CHL1 contributors: mct/npt - updated : 09-10-2019
HGNC name cell adhesion molecule with homology to L1CAM (close homolog of L1)
HGNC id 1939
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a signal peptide followed by 6 immunoglobulin (Ig) domains
  • four fibronectin type III (FNIII) domains
  • a single-pass transmembrane peptide
  • a 105-amino acid cytoplasmic domain
  • 21 potential N-glycosylation sites, more than 50 O-glycosylation sites
  • 22 N-myristoylation sites
  • a membrane-proximal motif (RGGKYSV) in the cytoplasmic domain, having novel functions necessary for SEMA3A-induced growth cone collapse and CHL1-dependent neurite outgrowth and branching in cortical embryonic neurons (Schlatter 2008)
  • two amidation sites and multiple phosphorylation sites
  • HOMOLOGY
    interspecies ortholog to murine Chl1
    homolog to Drosophila Nrg
    homolog to C.elegans Y54G2A.25
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • neuronal cell recognition molecule family
  • L1 subfamily of neural cell adhesion molecules
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,nucleus
    text
  • accumulates in presynaptic membranes and, in response to synapse activation, is targeted to synaptic vesicles by endocytosis (Leshchyns'ka 2006)
  • in neurons, L1CAM and CHL1 are mainly located in axonal membranes
  • basic FUNCTION
  • neuronal adhesion protein L1-CAM serving as a receptor for nerve growth-promoting proteins
  • adhesion molecule that regulates uncoating of clathrin-coated synaptic vesicles
  • maybe involved in cognitive and behavioral functions
  • having a function in thalamic axon responsiveness to ventral telencephalic cues, and playing a role with NRP1 in establishment of proper targeting of specific thalamocortical projections (Wright 2007)
  • able to recruit ezrin, a member of the ezrin-radixin-moesin (ERM) family of filamentous actin binding proteins to the plasma membrane (Schlatter 2008)
  • promotes Purkinje and granule cell survival and granule cell migration during cerebellar development (Jakovcevski 2009)
  • important for apical dendritic projection and laminar positioning of pyramidal neurons in caudal regions of the cerebral cortex (Demyanenko 2010)
  • cooperate with PAK1, PAK2, PAK3 kinase, most likely in independent pathways, in regulating morphological development of the leading process/apical dendrite of embryonic cortical neurons (Demyanenko 2010)
  • L1CAM and CHL1, are crucial for axonal guidance and maintenance of neural circuits
  • L1CAM and its close homolog CHL1 are neural cell adhesion molecules of the immunoglobulin superfamily
  • in the adult brain, L1CAM and CHL1 continue to play important roles in maintenance and regeneration of neural circuits
  • plays a dual role by either promoting or inhibiting neuritogenesis
  • ligand-induced and lipid raft-dependent regulation of CHL1 adhesion via Ca(2+)-dependent remodeling of the CHL1-beta2 spectrin complex and CHL1 endocytosis are required for CHL1-dependent neurite outgrowth
  • is involved in the regulation of recovery after spinal cord injury
  • is a novel intrinsic factor that is involved in carotid body (CB) function and in the ventilatory response to acute hypoxia (AH)
  • regulates neuronal migration and neurite overgrowth in the developing brain, while in mature neurons it accumulates in the axonal membrane and regulates synapse function via the clathrin-dependent pathways
  • CHL1 is a new modulator of the serotonergic system
  • DISC1 and CHL1 may engage in physical and functional interaction in neural development
  • plays important roles during nervous system development
  • roles for CHL1 in both axonal extension and repulsion, selectively of dopaminergic (DA) neurons, suggestive of a role in guidance towards forebrain targets and away from hindbrain nuclei
  • function as an important tumor suppressor with both anti-proliferation and anti-metastasis abilities, through NF2 and SEMA3B-Np1-mediated inhibition of AKT1 signaling pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • regulated by MAP kinase pathway
  • L1-CAM-mediated nerve growth by modulating ankyrin binding
  • direct or indirect interaction between CHL1 and ERM proteins mediates SEMA3A-induced growth cone collapse as well as neurite outgrowth and branching, which are essential determinants of axon guidance and connectivity in cortical development (Schlatter 2008)
  • L1CAM and CHL1 are physiological substrates for BACE1
  • BACE1 is responsible for CHL1 processing in the brain and synaptic membranes under physiological conditions
  • extracellular matrix-associated proteins vitronectin and plasminogen activator inhibitor-2 (SERPINB2) were identified as novel CHL1 interaction partners, promoting CHL1-induced neurite outgrowth and neuronal migration
  • PTCH1 is a novel CHL1-binding protein and CHL1 interacts with the first extracellular loop of PTCH1 via its extracellular domain
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL3PD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    putatively involved in in 3p- syndrome
    tumoral     --over  
    in lung adenocarcinomas and squamous cell carcinomas compared to neuroendocrine and large cell carcinomas of the lung
    tumoral     --low  
    by hypermethylation and that this epigenetic alteration is an independent prognostic factor in breast cancer
    Susceptibility
  • to schizophrenia
  • to infantile spasms (ISS)
  • Variant & Polymorphism SNP , other
  • Leu17Phe
  • CNV associated with infantile spasms (ISS)
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • adult Chl1(-/-) mice display behavioral traits similar to those observed in neuropsychiatric disorders of humans