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FLASH GENE
Symbol CADM1 contributors: mct/pgu - updated : 23-08-2013
HGNC name cell adhesion molecule 1
HGNC id 5951
Location 11q23.3      Physical location : 115.044.345 - 115.375.241
Synonym name
  • synaptic cell adhesion molecule
  • tumor supressor in lung cancer (see ST3)
  • immunoglobulin superfamily, member 4
  • nectin-like molecule 2
  • spermatogenic immunoglobulin superfamily
  • Synonym symbol(s) ST17, TSLC1, BL2, NECL2, SYNCAM, SYNCAM1, RA175, BL2, ST17, IGSF4, IGSF4A, Necl-2, MGC51880, MGC149785, sgIGSF
    DNA
    TYPE functioning gene
    STRUCTURE 330.90 kb     10 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map cen - D11S144 - D11S4501 - D11S145 - D11S4517 - D11S1256 - D11S4111 /CADM1 - D11S4502 - D11S4484 - D11S1885 - D11S4500 - D11S4507 - qter
    regionally located situated in a common loss of heterozygosity region (see IGBF4)
    RNA
    TRANSCRIPTS type messenger
    text same ORF
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 splicing 4324 - 442 - 2009 19854157
    also called IGSF4L
    9 - 4240 - 414 - 2009 19854157
  • also called IGSF4S
  • - - - - - - 2013 23620770
  • key receptor mediating mast cells adhesion to airway smooth muscle cells and lung fibroblasts
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrinepancreasislet of Langerhans  highly
    Nervousbrain   highly Homo sapiens
    Reproductivemale systemtestis  highly Homo sapiens
    Respiratorylung   highly Homo sapiens
    Skin/Tegumentskin appendageshairbulb highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    Nervousneuron
    Reproductivespermatid
    Reproductivespermatocyte
    Skin/Tegumenthair follicle cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, perinatal
    Text expressed in the late embryonic and early postnatal brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal signal peptide
  • three Ig-C2-like domains
  • a transmembrane segment (TM1)
  • cytoplasmic domain with a binding motif to the protein 4.1 family of molecules
  • cytoplasmic domain with a type II PSD95/Dlg/ZO-1 (PDZ)-binding motif (BM) for associating with other intracellular proteins
  • a C-terminal transmembrane domain, and an intracellular type II PDZ binding domain and band 4.1 binding domain
  • extracellular domain of CADM1 undergoing homophilic or heterophilic interaction with CADM3, PVRL3, and CRTAM (class-I MHC-restricted T cell-associated molecule)
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Igsf4
    intraspecies homolog to NCAM1,NCAM2
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • nectin family
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    text integral membrane protein, localized to both sides of the synaptic cleft
    basic FUNCTION
  • potentially involved in cell-surface recognition during synapse assembly
  • involved in the suppression of lung tumor formation and metastasis
  • playing an important role in normal cell-cell interaction
  • a central effector gene for controlling the biologic aggressiveness of the tumor and that it is an essential biomarker for predicting patient prognosis
  • plays an important role in meningioma pathogenesis
  • functions as a glioma tumor suppressor
  • may be playing a role in normal spermatogenesis
  • synaptic cell adhesion molecule sufficient for promoting the formation of presynaptic terminals and inducing the functional synapse
  • mediates nerve-mast cell attachment and communication through homophilic binding
  • may be involved in hormone secretion from islet cell tumors
  • involved in regulating epidermal stem cell quiescence and location
  • selectively involved in endothelial cell migration, suggesting a role in endothelial barrier repair
  • tumor suppressor, involved in cell adhesion and preferentially inactivated in invasive cancer
  • involved in the formation of epithelia-like cell structure with EPB41L3 and MPP2, while loss of its function could cause morphological transformation of cancer cells
  • plays an important role in the formation of the epithelial cell structure with mature cell adhesion
  • CADM1 complex may play a key role in the formation of the epithelia-like cell structure, whereas inactivation of the components of the complex would be a key step in malignant progression of cancer
  • negatively regulates the morphological complexity of migrating growth cones
  • acts in developing neurons to shape migrating growth cones and contributes to the adhesive differentiation of their axo-dendritic contacts
  • contributes to ERBB4 receptor-mediated control of female sexual development
  • self-assembles laterally via its extracellular, membrane-proximal immunoglobulin (Ig) domains 2 and 3
  • function for CADM1 in suppressing metastasis by sensitizing tumor cells to immune surveillance mechanisms
  • promotes the formation of presynaptic terminals and induces functional synapses in the central nervous system
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms a tripartite protein complex with EPB41L3 and MPP1, MPP2, MPP3
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • intracellular PDZ-domain proteins
  • associating with MPP3(interaction dependent on the presence of a PDZ-binding motif at the carboxyl terminus of TSLC1)
  • associates with an actin-binding protein, EPB41L3, and a scaffold protein, membrane protein palmitoylated 3 MPP3, MPP2, MPP1
  • recruits NMDA receptors via protein EPB41L3
  • interaction with PTK2 (PTK2 is a binding partner and effector in shaping growth cones)
  • interacting with TIAM1 (cytoplasmic domain of CADM1 directly interacted with the PDZ domain of Tiam1 and induced formation of lamellipodia through Rac activation in HTLV-I-transformed cell lines as well as adult T-cell leukemia cell lines)
  • EPB41L3 binds to CADM1 through conserved residues in a well defined hydrophobic pocket in the structural C-lobe of the EPB41L3 FERM domain
  • ADAM10 mediates endogenous CADM1 shedding
  • triggers a retrograde signal regulating active zone composition via CADM1
  • interacts with ERBB4 and regulates the development of excitatory synapses via the regulation of ERBB4 activity in GABAergic neurons
  • interaction of CADM1 with ERBB3 inhibits the NRG1-induced ERBB3/ERBB2 signaling in epithelial cells
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in breast cancer, neuroblastoma, non small cell lung cancer, hepatocellular, nasopharyngeal and pancreatic carcinomas
    tumoral       loss of function
    by promoter hypermethylation in non small cell lung cancer, hepatocellular carcinoma, pancreatic carcinoma, and prostate tumor
    tumoral     --low  
    in lung adenocarcinoma associated with lower patient survival, supporting its role as a tumor suppressor and in esophageal squamous cell carcinoma with a poor prognosis
    tumoral       loss of function
    by hypermethylation in premalignant cervical intraepithelial neoplasia by infection with high-risk human papillomavirus (HPV) types, in progression
    tumoral     --low  
    in meningioma, associated with decreased survival, and in the atypical meningiomas
    constitutional       loss of function
    causes male infertility
    tumoral     --low  
    in metastatic lymph node nasopharyngeal carcinoma
    tumoral     --over  
    frequent overexpression in lung adenocarcinoma
    tumoral     --over  
    resulted in reduced proliferation and increased levels of CASK and CDH1 at the leading edge of healing wounds
    tumoral     --low  
    frequently observed in various cancers, including non-small cell lung cancer (NSCLC) especially in their invasive lesions
    tumoral     --low  
    is a critical event in neuroblastoma pathogenesis resulting in tumour progression and unfavourable patient outcome
    tumoral     --low  
    by hypermethylation in squamous cell carcinomas (SCCs)of uterine cervix
    tumoral     --over  
    in adult T-cell leukemia-lymphoma (ATL) cells
    Susceptibility to Autism Spectrum Disorder (ASD)
    Variant & Polymorphism other mutationslocated in the third immunoglobulin (Ig3) domain essential for homophilic or heterophilic transactive interaction associated to Autism Spectrum Disorder (likely these mutations cause the loss of function, resulting in the impaired synaptogenesis, which is closely associated with the pathogenesis of ASD)
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Cadm1-knock out (KO) mice exhibit smaller cerebella with decreased number of synapse of Purkinje cells and some ASD-like symptoms, including impaired ultrasonic vocalization
  • epidermal overexpression of Cadm1 in transgenic mice led to increased autoimmune alopecia susceptibility relative to nontransgenic littermate controls