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FLASH GENE
Symbol MAGEL2 contributors: mct - updated : 20-11-2024
HGNC name MAGE-like 2
HGNC id 6814
Corresponding disease
AMCN5 arthrogryposis multiplex congenita, neurogenic 5
PWLAD Prader-Willi like with autism spectrum disorder
PWS Prader-Willi syndrome
Location 15q11.2      Physical location : 23.888.697 - 23.892.993
Synonym name
  • necdin-like 1
  • melanoma antigen (MAGE)-like 2
    • Synonym symbol(s) NDNL1, nM15, PWLS, SHFYNG, SYS
    DNA
    TYPE functioning gene
    SPECIAL FEATURE
    text associated with a 5'differentiated methylated region (DMR)
    STRUCTURE 4.30 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - MKRN3 - NDN - MAGEL2 - SNURF - SNRPN - PAR5 - IPW - PAR1 - UBE3A - NDNL2 - ATP10A - APBA2 - qter
    Authors Lee (00), Herzing (02)
    regionally located 41kb telomeric to NDN (head to tail) within the PWCR region
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 4298 - 1249 - 2000 10915770
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine    Mus musculus
    Nervousbraindiencephalonhypothalamussuprachiasmatic nucleipredominantly Mus musculus
     brainmidbrain    Mus musculus
     brainforebrain    Mus musculus
     gangliasensory gangliadorsal root   Mus musculus
    Reproductivefemale systemplacenta    Mus musculus
     male systembulbourethral gland    Mus musculus
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text several tissues (brain, kidney, liver, lung)
    IMPRINTING maternally
    text
  • paternally in brain fetal and adult
  • only expressed from the paternal allele
    • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal half of MAGEL2 might be required for the interaction with regulators of RNA metabolism
  • a C terminal domain of homology with the MAGE (essentially MAGED1) and NDN proteins
    • HOMOLOGY
    Homologene
    FAMILY MAGE gene family
    CATEGORY antigen
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    text
  • MAGEL2 shuttles between the cytoplasm and the nucleus
    • basic FUNCTION
  • induces the redistribution of the subcellular localization of CLOCK towards the cytoplasm, in contrast to the nucleus-directed effect of ARNTL on CLOCK subcellular localization
  • normally promotes potentially negative feedback regulation of the cellular circadian cycle, through interactions with key core circadian rhythm proteins
  • MAGED1 and MAGEL2 are thus both essential for the proper regulation of food intake
  • ubiquitin ligase activity of MAGEL2-TRIM27 is important for proper retrograde transport
  • has an essential role in neuronal development
  • plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway
  • plays a key role in modulating bone remodeling and mass in PWS by affecting N-oleoyl serine (OS) levels and activity
  • act as a tissue-specific regulator of the retromer-dependent endosomal protein recycling pathway and, by doing so, ensures proper secretory granule formation and maturation
  • involvement of MAGEL2 in biological processes such as RNA stabilization, chromosome condensation, and transcription
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • E3 RING ubiquitin ligase, MAGEL2-TRIM27, localizes to endosomes through interactions with the retromer complex
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MAGEL2 interacts with ARNTL and with PER2
  • TRIM27 was identified as a major binding partner of MAGEL2, and MAGEL2-TRIM27 is likely required for endosome-to-Golgi retrograde transport
  • bind USP7 and TRIM27 proteins, thus forming the MUST complex
  • MAGEL2 was identified to interact with VPS35 and VPS26A two components of the endosomal retromer complex
  • VPS35 recruits MAGEL2-TRIM27 to retromer-positive endosomes by binding to MAGEL2
  • NDN necdin, MAGED1, MAGEF1 and MAGEL2 bound to PIAS1 but not to NSMCE2 or CBX4
  • interacts with proteins involved in transcription regulation and RNA metabolism (PMUID: 38908375)
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PWS , PWLAD , AMCN5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in the hippocampus of patients with incipient Alzheimer disease
    constitutional       loss of function
    leads to the disruption of hypothalamic feeding circuits, an effect that appears to be independent of the neurodevelopmental effects of leptin and ghrelin and likely involves a direct neurotrophic effect of MAGEL2
    Susceptibility
    Variant & Polymorphism
    Candidate gene regulation of normal circadian rhythm
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Magel2-null mice exhibit neonatal growth retardation, excessive weight gain after weaning, and increased adiposity with altered metabolism in adulthood as seen in PWS patients
  • mice lacking Magel2 display increased weight gain with excess adiposity and other defects suggestive of hypothalamic deficiency
  • paternally Magel2-null mice have reduced embryonic viability but otherwise normal embryonic growth in survivors, followed by post-natal growth retardation and excessive weight gain, recapitulating aspects of the PWS phenotype