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FLASH GENE
Symbol ALCAM contributors: mct/npt - updated : 24-08-2016
HGNC name activated leukocyte cell adhesion molecule
HGNC id 400
DNA
TYPE functioning gene
STRUCTURE 210.20 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 2075 - 133 constitutively produced by epithelial ovarian cancer cells 2004 15496415
  • also called sALCAM
  • soluble ALCAM , consisting of most of the extracellular domain
  • contains the single amino-terminal Ig-like domain of ALCAM and lacks a transmembrane domain
  • has an independent effect on cell migration in addition to modulating ALCAM function, and modulates endothelial cell function
  • 16 - 4760 65.1 583 - 2004 15496415
    15 - 4884 - 570 - 2004 15496415
    14 - 2961 - 555 - 2004 15496415
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Endocrineparathyroid   highly
    Hearing/Equilibriumearinnercochlea moderately
    Lymphoid/Immunelymph node   moderately
    Nervousbrain   moderately
     nerve   highly
    Respiratoryrespiratory tracttrachea  highly
     respiratory tractlarynx  moderately
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  moderately Homo sapiens
    Connectivebone  moderately Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell Homo sapiens
    Skeletonosteoblast Homo sapiens
    Visualganglion cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a CD6 binding site located in the N-terminal Ig-like domain
  • five extacellular Ig-like domains
  • three Ig-like C2-type (immunoglobulin-like) domains
  • two Ig-like V-type (immunoglobulin-like) domains
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus Alcam (93.31 pc)
    homolog to murine Alcam (92.97 pc)
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton
    text
  • localized at intercellular junctions in epithelium presumably as part of the adhesive complex that maintains tissue architecture (Ofori-Acquah 2008)
  • dynamic association between ALCAM and the actin cytoskeleton
  • type I transmembrane protein
  • basic FUNCTION
  • involved in neurite extension by neurons via heterophilic and homophilic interactions
  • may play a role in the binding of T- and B-cells to activated leukocytes, as well as in interactions between cells of the nervous system
  • directly involved in monocyte cell lines transendothelial migration
  • protecting breast cancer cells against apoptosis and autophagy
  • integrative role in orchestrating cell adhesion, growth, invasion, and proteolysis in the tumor tissue microenvironment (van Kilsdonk 2008)
  • involved in cell migration and adhesion (Davies 2008)
  • associated with cell migration and leukocyte invasion into the vessel wall
  • cholesterol-induced apoptosis in monocytes is accompanied by reduced expression of ALCAM and attenuated monocyte migration
  • cell adhesion molecule that is present on extending axons and has been shown to be crucial for elongation and navigation of retinal ganglion cell (RGC) axons
  • growth cone translation of ALCAM is crucial for the enhanced elongation of axons extending in contact with ALCAM protein
  • ALCAM expression on osteoblast is directly correlated with RUNX2 expression and high hematopoiesis enhancing activity (HEA)
  • CELLULAR PROCESS cell life, antiapoptosis
    cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ADAM17 (ALCAM shedding by the metalloprotease ADAM17 is involved in motility of ovarian carcinoma cells)(Rosso 2007)
  • ALCAM synergizes with NGF to induce neuronal differentiation, raising the possibility that it functions not only as an adhesion molecule but also in the modulation of growth factor signaling in the nervous system
  • ALCAM directly associates with the tetraspanin CD9 on the leukocyte surface in protein complexes that also include the metalloproteinase ADAM17/TACE
  • contribute to DC-T-cell adhesion, stabilize DC-T-cell contacts and form a mechanical link between CD6 and the actin cortex to strengthen cell adhesion at the immunological synapse
  • ALCAM stably interacts with actin by binding to SDCBP and EZR, and interaction with the ligand CD6 further enhances these multiple interactions
  • AKT1 is an inter-mediator between the upstream regulator, ALCAM, and downstream effector, FOXO1, in liver cancer cells
  • interaction of LGALS1 and LGALS3 with CD6 and CD166/ALCAM might modulate some relevant aspects of T cell physiology
  • interaction between CD6 and ALCAM regulating T-cell activation
  • LGALS8 interacts with ALCAM at the surface of breast cancer cells through glycosylation-dependent mechanisms
  • PRMT1 is overexpressed in human melanoma, and may regulate tumor growth and metastasis via targeting ALCAM
  • CD6 facilitates adhesion between T cells and antigen-presenting cells through its interaction with ALCAM, and physically associates with the T cell receptor (TCR) at the center of the immunological synapse
  • SH3GL3 associates with ALCAM-containing early endocytic carriers and physically interacts with the cargo
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    ALCAM-ALCAM interactions protects breast cancer cells against apoptosis and autophagy
    tumoral     --low  
    in breast cancer tissue are known to correlate with poor prognosis, and patients who develop skeletal metastasis tend to have the lowest levels of ALCAM transcripts in their breast cancers (Davies 2008)
    tumoral     --over  
    in breast cancer and high membranous expression of ALCAM probably resulted in weakened adherent ability and metastasis
    tumoral     --over  
    in papillary and medullary thyroid cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene novel serum biomarker in human pancreatic tumors which is associated with cell adhesion, growth and chemoresistance (Hong 2010)
    Marker
    Therapy target
  • therapeutic potential for a secreted variant (sALCAM)
  • SystemTypeDisorderPubmed
    cancerreproductivebreast
    potential novel breast cancer indicator and therapeutic target
    ANIMAL & CELL MODELS
  • CD166(-/-) mice exhibited a modest increase in trabecular bone fraction (42p100), and increases in osteoid deposition (72p100), Osteoblast number (60p100), and bone formation rate (152p100)