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FLASH GENE
Symbol MCAM contributors: mct/npt - updated : 15-01-2016
HGNC name melanoma cell adhesion molecule
HGNC id 6934
Location 11q23.3      Physical location : 119.179.234 - 119.187.840
Synonym name
  • cell surface MUC18 precursor
  • Gicerin
  • melanoma-associated antigen MUC18
  • S-endo 1 endothelial-associated antigen
  • CD146 antigen
  • Synonym symbol(s) CD146, MUC18, MU18
    DNA
    TYPE functioning gene
    STRUCTURE 8.61 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    BCL9L 11q23.3 B-cell CLL/lymphoma 9-like UPK2 11q23 uroplakin 2 LOC283150 11q23.3 hypothetical protein LOC283150 DLNB14 11q23.3 similar to DLNB14 RPS25 11q23.3 ribosomal protein S25 TRAPPC4 11q23.3 trafficking protein particle complex 4 SLC37A4 11q23.3 solute carrier family 37 (glycerol-6-phosphate transporter), member 4 HYOU1 11q23.1-q23.3 hypoxia up-regulated 1 VPS11 11q23 vacuolar protein sorting 11 (yeast) HMBS 11q23.3 hydroxymethylbilane synthase H2AFX 11q23.3 H2A histone family, member X DPAGT1 11q23.3 dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GlcNAc-1-P transferase) KIAA0285 11q23.3 dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GlcNAc-1-P transferase) MIZF 11q23.3 MBD2 (methyl-CpG-binding protein)-interacting zinc finger protein ABCG4 11q23.3 ATP-binding cassette, sub-family G (WHITE), member 4 NOD9 11q23.3 NOD9 protein PDZK2 11q23.3 PDZ domain containing 2 LOC387812 11 LOC387812 CBL 11q23.3 Cas-Br-M (murine) ecotropic retroviral transforming sequence MCAM 11q23.3 melanoma cell adhesion molecule RNF26 11q23 ring finger protein 26 C1QTNF5 11q23.3 C1q and tumor necrosis factor related protein 5 MFRP 11q23 membrane frizzled-related protein USP2 11q23.3 ubiquitin specific protease 2 LOC94105 11q22.3-q23 Thy-1 co-transcribed THY1 11q23.3 Thy-1 cell surface antigen LOC387813 11 similar to keratin 8; cytokeratin 8; keratin, type II cytoskeletal 8 PVRL1 11q23-q24 poliovirus receptor-related 1 (herpesvirus entry mediator C; nectin)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 3332 - 646 - 2010 20448216
  • long isoform (MCAMl)
  • in subconfluent endothelial progenitors (EPCs), was intracellular
  • - - - - - - 2010 20448216
  • short isoform
  • in subconfluent endothelial progenitors (EPCs), localized in the nucleus and at the migrating edges of the membrane
  • involved in EPC adhesion to activated endothelium, migration, and proliferation, with a paracrine secretion of interleukin-8 or angiopoietin 2
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   predominantly
    Digestiveintestinesmall intestine  highly
     mouth   highly
    Endocrineadrenal gland   highly
    Reproductivefemale systemuteruscervix highly
     male systemprostate   
    Respiratorylung    
     respiratory tracttrachea  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningendothelium  
    Muscularsmooth   
    Muscularstriatumcardiac  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    cell lineage
    cell lines melanoma
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three immunoglobulin-like C2 type domain
  • two immunoglobulin-like V type domain
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus Mcam (75.54 pc)
    homolog to murine Mcam (76.63 pc)
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
    text
  • type I membrane protein
  • localized at endothelial cell junctions
  • basic FUNCTION
  • adhesion molecule active in neural crest cells during embryonic development
  • play an important role in developing and malignant progression of prostate cancer
  • may play a role in uveal melanoma growth (Lai 2007)
  • plays a critical role in cell proliferation and activation, and contributes to inflammatory reactions (Wang 2008)
  • might be a novel marker for renal tubular epithelial cells, correlating with cell proliferation and cell-cell conjunctions (Wang 2008)
  • endothelial cell adhesion molecule, implicated in blood vessel formation (Zheng 2009)
  • required for the activation of MAPK14/IKK/NF kappaB signaling cascade and up-regulation of NF kappaB downstream pro-angiogenic genes (Zheng 2009)
  • might serve as not just a cell adhesion molecule but also a membrane signal receptor in tumor-induced angiogenesis (Zheng 2009)
  • its expression differentiates between perivascular versus endosteal localization of non-hematopoietic bone marrow mesenchymal stem cells (BM-MSCs) population
  • is a unique activator of epithelial-mesenchymal transition (EMTs) and significantly correlates with triple-negative breast cancer
  • is highly specific for myogenic progenitor cells only in primary tissue
  • its expression strongly correlates with myogenic activity in human fetal muscle
  • is a new coreceptor for KDR and is therefore a promising target for blocking tumor-related angiogenesis
  • actively involved in miscellaneous processes, such as development, signaling transduction, cell migration, mesenchymal stem cells differentiation, angiogenesis and immune response
  • endothelial MCAM plays an active role in the CNS-directed extravasation of encephalitogenic T cells
  • involved in cell-cell cohesion and permeability (Bardin 2009)
  • adhesion molecule localized at endothelial cell junctions and facilitates cell-cell interactions
  • inhibits canonical Wnt signalling by promoting CTNNB1 degradation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CD146 dimerization occurs in living cells and is regulated within the tumor microenvironment, implying that dimerization of CD146 may be associated with malignancy (Bu 2007)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with SHROOM1 (SHROOM1 is involved in linking MCAM to the cytoskeleton
  • MCAM recruits ARHGDIA through ERM proteins and thus sequesters ARHGDIA from RHOA, which leads to upregulated RHOA activity and increased melanoma cell motility
  • promotes breast cancer progression by induction of EMTs via the activation of RHOA and up-regulation of SNAI2 (
  • MCAM interacts directly with KDR on endothelial cells
  • LGALS1 is a novel ligand for MCAM and this interaction protects, in vitro, endothelial cells against apoptosis induced by LGALS1
  • binds to angiomotin to stimulate a proangiogenic response
  • acting potentially as a functional WNT5A receptor in regulating cell migration and convergent extension, turning off the canonical Wnt signalling branch
  • ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM
  • cell & other
    REGULATION
    Other regulated by the inflammatory cytokine TNF(Bardin 2009)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    overexpressed in:
  • malignant melanoma in progression
  • prostate cancer during intiation (high grade PIN) and progression to carcinoma
  • metastatic cell lines and metastatic carcinoma
  • constitutional     --over  
    on activated endothelium during angiogenesis (Bu 2007)
    tumoral     --low  
    by promoter methylation, directly correlated with tumor stage (pT3+pT4) in primary prostate carcinoma (Liu 2008)
    constitutional       loss of function
    damages pulmonary endothelial integrity, leading to COPD/emphysema
    Susceptibility
    Variant & Polymorphism
    Candidate gene MCAM promoter hypermethylation deserves further attention as a potential diagnostic prostatic DNA marker in human prostate cancer (Liu 2008)
    Marker
  • novel bio-marker for angiogenesis and for cancer
  • could represent both an attractive biomarker of placental vascular development
  • can be used as a molecular marker to determine the prognosis of ovarian cancer
  • Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    targeting endothelial MCAM attenuates neuroinflammation by limiting lymphocyte extravasation to the CNS
    reproductionpregnancy 
    therapeutic target in pregnancy complications associated with pathological angiogenesis
    cancerreproductiveovary
    therapeutic target in metastatic ovarian cancer
    cancerreproductivebreast
    can be used as a potential therapeutic target for breast cancer, especially for TNBC
    ANIMAL & CELL MODELS