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FLASH GENE
Symbol CUBN contributors: mct - updated : 12-12-2018
HGNC name cubilin (intrinsic factor-cobalamin receptor)
HGNC id 2548
Corresponding disease
MGA2 juvenile megaloblastic anemia
Location 10p13      Physical location : 16.865.965 - 17.171.816
Synonym name
  • cubilin
  • intrinsic factor-vitamin B12 receptor
  • Synonym symbol(s) GIFR, IFCR, GP280, FLJ90055, FLJ90747, MGA1
    DNA
    TYPE functioning gene
    STRUCTURE 306.53 kb     68 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D10S1653 - D10S1763 - D10S1661 - D10S674 - D10S1477 - D10S1476 - [D10S504 - CUBN - D10S1714 ] - D10S548 - cen
    Authors Aminoff (99)
    Text [MGA1 ]
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    68 - 11933 - 3623 - -
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis    Mus musculusAdult
     male systemtestis    Mus musculusFetal
    Urinarykidneynephronrenal capsuleglomerulus  Homo sapiens
     kidneytubuleconvoluted tubuleproximal tubulehighly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatid Mus musculusAdult
    Reproductivespermatid Mus musculusFetal
    Reproductivespermatocyte Mus musculusFetal
    Reproductivespermatogonia Mus musculusFetal
    Urinarypodocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • eight EGF repeats followed by 27 CUB domains
  • two distinct ligand binding domains(for IF-CBL and albumin)
  • lacking a transmembrane domain but anchoring to apical membranes by forming complexes with AMN or Megalin
  • HOMOLOGY
    interspecies homolog to rattus Cubilin
    Homologene
    FAMILY papain cysteine protease family
    CATEGORY receptor membrane , transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    text colocalizing with megalin (LRP2) in the kidney proximal tubule
    basic FUNCTION
  • multiligand receptor for cobalamin, iron and protein
  • facilitating the endocytic process by sequestering steroid-multiligand complexes on the cell surface before megalin-mediated internalization of te cubilin-bound ligand
  • also high affinity apoprotein APO A-1 receptor facilitating endocytosis of high-density lipoprotein (HDL)
  • with LRP2, are multifunctional endocytotic receptors expressed in many absorptive epithelia
  • role for cubilin as a drug receptor for aminoglycosides and possibly other ototoxic substances
  • multiligand endocytic receptor critical for the intestinal absorption of vitamin B12 and renal protein reabsorption
  • is a receptor for vitamins and various protein ligands
  • potential role of CUBN in endocytosis during early spermiogenesis
  • may likely participate in the endocytotic uptake of nutrients in germ cells and somatic cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS endocytosis transport
    PATHWAY
    metabolism
    signaling
    a component
  • forming a complex (cubam) with AMN (amnionless) directing subcellular localization and endocytosis of cubilin with its ligand
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with LRP2
  • FGF8, a key mediator of cell survival, migration, proliferation, and patterning in the developing head, is a high affinity ligand for CUBN
  • LRP2 and CUBN may be important in human maternal-fetal transfer, and they increase across gestation to facilitate this function
  • CUBN functions as a multi-ligand receptor by binding to the transmembrane protein, AMN and AMN -mediated glycosylation is crucial for cell surface targeting of CUBN in renal and intestinal cells
  • CUBN-FGF8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MGA2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    leads to urinary loss of albumin and APOA1
    Susceptibility
  • to diabetes-associated end stage renal disease
  • to albuminuria
  • Variant & Polymorphism SNP
  • cubilin rare variant associated with diabetes-associated end stage renal disease
  • missense CUBN variant associating with levels of albuminuria in both the general population and in individuals with diabetes
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousurinarychronic kidney disease
    therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL
    ANIMAL & CELL MODELS
  • cubilin HT mice displayed significantly decreased blood levels of albumin, ApoA1, and HDL