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FLASH GENE
Symbol L1CAM contributors: mct/shn - updated : 17-01-2012
HGNC name L1 cell adhesion molecule
HGNC id 6470
Corresponding disease
HSAS X-linked hydrocephalus, or stenosis of the aqueduct of Sylvius
MASA MASA syndrome
SPG1 X-linked spastic paraplegia
Location Xq28      Physical location : 153.126.973 - 153.141.399
Synonym name
  • antigen identified by monoclonal antibody R1
  • CD171 antigen
  • neural cell adhesion molecule L1
  • Synonym symbol(s) MIC5, CAML1, CD171, HSAS1, S10, CD171, N-CAML1, HSAS, MASA, SPG1, CAML1, N-CAM-L1, NCAM-L1, L1/NgCAM, L1
    DNA
    TYPE functioning gene
    STRUCTURE 14.43 kb     27 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - DXS8061 - DXS8087 - L1CAM - DXS1073 - qter
    Physical map
    TREX2 Xq28 three prime repair exonuclease 2 LOC389904 X similar to Extracellular matrix protein 2 precursor (Matrix glycoprotein SC1/ECM2) BGN Xq28 biglycan ATP2B3 Xq28 ATPase, Ca++ transporting, plasma membrane 3 MGC29729 Xq28 hypothetical protein MGC29729 LOC340598 Xq28 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) DUSP9 Xq28 dual specificity phosphatase 9 LOC347544 Xq28 similar to ribosomal protein L18a; 60S ribosomal protein L18a MGC45419 Xq28 Similar to calcium/calmodulin-dependent protein kinase 1, beta SLC6A8 Xq28 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 BCAP31 Xq28 solute carrier family 6 (neurotransmitter transporter, creatine), member 8 ABCD1 Xq28 ATP-binding cassette, sub-family D (ALD), member 1 PLXNB3 Xq28 plexin B3 STK23 Xq28 serine/threonine kinase 23 IDH3G Xq28 isocitrate dehydrogenase 3 (NAD+) gamma SSR4 Xq28 signal sequence receptor, delta (translocon-associated protein delta) KIAA1444 Xq28 LU1 protein HCP45 Xq28 cytochrome c, somatic pseudogene L1CAM Xq28 L1 cell adhesion molecule (hydrocephalus, stenosis of aqueduct of Sylvius 1, MASA (mental retardation, aphasia, shuffling gait and adducted thumbs) syndrome, spastic paraplegia 1) AVPR2 Xq28 arginine vasopressin receptor 2 (nephrogenic diabetes insipidus) ARHGAP4 Xq28 Rho GTPase activating protein 4 ARD1 Xq28 ARD1 homolog, N-acetyltransferase (S. cerevisiae) RENBP Xq28 renin binding protein HCFC1 Xq28 host cell factor C1 (VP16-accessory protein) CXorf12 Xq28 chromosome X open reading frame 12 IRAK1 Xq28 interleukin-1 receptor-associated kinase 1 MECP2 Xq28 methyl CpG binding protein 2 (Rett syndrome)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    27 - 5034 - 1253 - 2010 20543863
  • lacks a neuron-specific exon in the 3prime region
  • 27 polyA site 5046 140 1257 typical of low-REST neural cells 2010 20543863
  • L1-FL
  • only isoform that can promote cell proliferation and tumour growth
  • plays key roles in survival/migration, outgrowth/fasciculation/regeneration of axons, synaptic plasticity
  • 26 splicing 5019 - 1248 - 2010 20543863
    lacking exon 27 and tyrosine based sorting motif
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain    
     nerve    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunedendritic cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • six repeats of the Ig C2 domain
  • five fibronectin FN, type III repeats
  • a transmembrane, highly conserved cytoplasmic domain
  • an intracellular domain L1 highly conserved
  • RGD integrin binding site in the sixth Ig domain, important for nuclear signaling, and is a binding site for integrins
  • conjugated GlycoP , PhosphoP
    HOMOLOGY
    interspecies ortholog to L1cam, Mus musculus
    ortholog to L1cam, Rattus norvegicus
    ortholog to L1CAM, Pan troglodytes
    Homologene
    FAMILY
  • transmembrane molecule of the Ig superfamily
  • CATEGORY adhesion , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • in neurons, L1CAM and CHL1 are mainly located in axonal membranes
  • basic FUNCTION
  • playing a role in nervous system development, neuronal migration and differentiation
  • playing a role in in corticospinal tract development
  • neural cell adhesion molecule that has been shown to help guide nascent axons to their targets (
  • important for cell migration and axon outgrowth
  • involved in IL-1&
  • 946;-mediated caspase inhibition in chemoresistant PDAC cells (
  • implicated in the regulation of dendritic cells trafficking
  • the soluble ectodomain of L1CAM promotes cell migration (, protects cells from apoptosis (, stimulates endothelial cell survival ( and acts as a proangiogenic factor
  • involved in proliferation, invasion and metastasis both in vitro and in vivo (
  • L1CAM cytoplasmic domain (L1CD) is involved in L1CAM trafficking, neurite branching, signaling, and interactions with the cytoskeleton (
  • activating IL1B and increased IL1B levels were instrumental for sustained NFKB activation
  • its ubiquitination might be involved in L1CAM-dependent functions in processes like cell migration and growth cone motility
  • its trafficking is regulated by ubiquitin, providing a novel and additional mechanism regulating L1CAM presence at the cell surface
  • regulates DNA damage checkpoint responses and radiosensitivity of Glioblastomas stem cells through nuclear translocation of L1CAM intracellular domain
  • L1CAM and CHL1, are crucial for axonal guidance and maintenance of neural circuits
  • in the adult brain, L1CAM and CHL1 continue to play important roles in maintenance and regeneration of neural circuits
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , nervous system
    text a key player in the development of the nervous system, regulating cell–cell interactions, neuronal cell migration and the neurite outgrowth of Schwann cells and axons as well as neurite fasciculation and myelination (
    PATHWAY
    metabolism
    signaling
    kinase activity
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 440-kD ankyrinB (
  • ezrin, AP2, ERM proteins (
  • neuropilin-1 (
  • Numb (
  • alphavbeta3-integrin (
  • RanBPM (
  • fibroblast growth factor receptor 1, FGFR1 (
  • NSG1 is a regulator of L1CAM sorting in somatodendritic endosomes
  • EZR, TAFP2A
  • can interact with itself (homophilic) and with heterophilic ligands such as integrins, CD24, neurocan, neuropilin-1 and other members of the neural cell adhesion family
  • EGFR
  • RGD-binding integrins (
  • regulates expression of NBS1, a critical component of the MRE11-RAD50-NBS1 (MRN) complex that activates ataxia telangiectasia mutated (ATM) kinase and early checkpoint response
  • REST control of L1CAM occurs by two mechanisms, transcription and alternative splicing v
  • TGFB1-dependent L1CAM expression has an essential role in macrophage-induced apoptosis resistance and cell migration of human intestinal epithelial cells
  • L1CAM and CHL1 are physiological substrates for BACE1 (pMID: 22692213)
  • RABGEF1 regulates the endocytic trafficking pathway of ubiquitinated neural cell adhesion molecule L1CAM
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) HSAS , MASA , SPG1
    related resource L1CAM Mutation Web Page
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    contiguous gene syndrome encompassing AVPR2, in patients with congenital hydrocephalus and diabetes insipidus
    tumoral     --low  
    by hypomethylation at the L1CAM CpG islands might induce L1CAM aberrant expression and contribute to the acquisition of aggressive tumor behavior in colorectal cancer
    tumoral     --over  
    in pancreatic cancer
    constitutional     --over  
    in intestinal epithelial cells in tissues from inflammatory bowel disease (IBD) patients but not in normal colonic tissues
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunology  
    offer novel therapeutic perspectives for the treatment of certain immunological disorders
    tumor  
    blockade of L1CAM binding to integrins abrogates L1CAM-induced tumour growth and reduces L1CAM-mediated chemoresistance
    cancer  
    a target for treatment of cancer with monoclonal antibodies
    ANIMAL & CELL MODELS
  • Cerebellar granule neurons expressing a deletion mutant of L1CAM lacking the cytoplasmic domain (hL1-1147) show a reduced branching of neurites (
  • L1-6D mutant mice, homozygous for a deletion removing the sixth immunoglobulin-like domain of L1cam, seldom display hydrocephalus on the 129/Sv background, while the same L1-6D mutation produces severe hydrocephalus on the C57BL/6J background (
  • L1cam knockout mice have hydrocephalus, a small cerebellum, hyperfasciculation of corticothalamic tracts, and abnormal peripheral nerves (
  • Enhanced expression of L1-CAM may contribute to the pain syndrome and perineural invasion and may correlate with poor overall survival in human pancreatic cancer (
  • L1CD mutant lines that lack the ankyrin-binding region display normal brain morphology but the expression of L1 protein in the adult is dramatically reduced and they show defects in motor function (
  • L1CAM expression leads to the activation of the nuclear factor (NF)-&
  • 954;B pathway, promoting cell proliferation in vitro and metastasis formation in vivo (