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FLASH GENE
Symbol CD46 contributors: mct - updated : 25-06-2011
HGNC name CD46 molecule, complement regulatory protein
HGNC id 6953
Location 1q32.2      Physical location : 207.925.382 - 207.968.860
Synonym name
  • antigen CD46, gp45-70 identified by monoclonal antibodies HuLym5 (E43), 122-2, J48
  • membrane cofactor protein (CD46, trophoblast-lymphocyte cross-reactive antigen)
  • antigen identified by monoclonal antibody TRA-2-10
  • CD46 antigen, complement regulatory protein
  • trophoblast leukocyte common antigen
  • measles virus receptor
  • Synonym symbol(s) MCP, D1S2240E, TLX, MIC10, TRA2.10, MGC26544
    DNA
    TYPE functioning gene
    STRUCTURE 43.48 kb     14 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map see RCA@
    RNA
    TRANSCRIPTS type messenger
    text
  • multiple isoforms are created following alternative splicing, with two major isoforms produced that are characterized by different cytoplasmic tailsthat contain signaling motifs; referred to here as Cyt1 and Cyt2
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 3402 43.7 392 - 2005 16254377
    13 - 3357 - 377 - 2005 16254377
    13 - 3309 - 377 - 2005 16254377
    12 - 3264 - 384 - 2005 16254377
    12 - 3312 - 362 - 2005 16254377
    11 - 3219 - 369 - 2005 16254377
    10 - 3177 - 355 - 2005 16254377
    10 - 3155 - 349 - 2005 16254377
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Endocrinepancreas    
    Reproductivefemale systemplacenta  highly
    Respiratorylung    
    Urinarybladder   highly
     kidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, trophoblast, pancreas
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four short consensus repeats
  • sushi structure (SRC) in the ectodomain (see F13B,SRCP1)
  • a serine-proline- rich domain
  • a cytoplasmic tail
  • two C-terminal splice variants Cyt1, and Cyt2
  • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY immunity/defense , antigen , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic,vesicle
    basic FUNCTION
  • playing a role in T-cell regulation and in T cell-mediated inflammatory responses
  • measles virus receptor
  • complement regulatory receptor for C3b and involved in regulation of complement activation
  • preventing complement activation in the syncytiotrophoblast layer of placenta
  • importance of CD46 as a cell target that might confer pathogens some biological advantages over the host
  • CD46-induced Tregs might play a role in intestinal immune homeostasis where they could dampen unwanted effector T cell responses through local IL10/granzyme B production
  • CD46-induced Treg enhance B-cell responses
  • surface receptor able to bind several different pathogens, and sufficient to induce autophagy
  • upon microorganism recognition, cell surface pathogen receptor that can directly trigger autophagy, a critical step to control infection
  • having complement and T cell regulatory functions in human cells
  • functions primarily as a complement control protein by preventing host cell lysis by autologous complement
  • ligation of CD46 influences T cell signaling, proliferation and fate
  • C3AR1 and CD46 activation via intrinsic generation of their respective ligands is an integral part of human Th1 (but not Th2) immunity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS reproduction/sex
    PATHWAY
    metabolism
    signaling
  • maybe involved in spermatozoa fusion with ovocyte during fertilization
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • multiple beta 1 integrins and tetraspans
  • MCP/CD3 costimulating VAV,RAC and extracellular signal-related kinase mitogen-activated protein kinase
  • CD46 ligation by complement or pathogens affects the biological functions of diverse immune cells such as macrophages, dendritic cells and T cells
  • cell & other
    REGULATION
    activated by upregulated on keratinocytes by TGFB1,TGFB2,TGFB3
    HBXIP, that upregulates CD46, CD55 and CD59 through p-ERK1/2/NFKB signaling to protect breast cancer from complement-dependent cytotoxicity
    Other cleaved by presenilin/gamma-secretase in response to Neisseria infection
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to measles
  • to familial hemolytic and uremic syndrome and meningococcal disease
  • Variant & Polymorphism SNP , insertion/deletion T2232C increasing the risk of atypical hemolytic and uremic syndrome
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS