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FLASH GENE
Symbol MAD2L1 contributors: mct/ - updated : 01-06-2018
HGNC name MAD2 mitotic arrest deficient-like 1 (yeast)
HGNC id 6763
Location 4q27      Physical location : 120.980.578 - 120.988.013
Synonym name
  • MAD2-like protein 1
  • mitotic arrest deficient, yeast, homolog-like 1
  • Synonym symbol(s) MAD2, HSMAD2
    DNA
    TYPE functioning gene
    STRUCTURE 7.44 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - FABP2 FABP2 - (D4S2347 ,MAD2L1 ) - CCNA2 - qter
    regionally located in the 5q-syndrome region
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1453 - 205 - 2008 17621272
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Nervousbrain    
    Reproductivefemale systemuteruscervix highly
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, checkpoint, M exit
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a DNA HORMA motif
  • HOMOLOGY
    interspecies homolog to mitotic arrest deficient yeast
    homolog to murine Mad2l1
    Homologene
    FAMILY
  • MAD2 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,centromere
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text localise to kinetochores with BUB1B and MAD1L1
    basic FUNCTION
  • involved in the cell cycle control at mitotic spindle assembly checkpoint
  • is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate
  • preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate
  • tumor suppressor gene also required for somatic cell viability (loss of MAD2 causing pemature CCNB1 degradation and mitotic failure in somatic cells)
  • TPR, and the spindle assembly checkpoint (SAC) protein MAD2L1 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells
  • involved in the mitotic spindle checkpoint pathway
  • exploits the two-state behavior of MAD2L1 to block its activation by acting as an "anti-MAD2L1"
  • acting in a surveillance mechanism that mediates a metaphase delay in response to nonexchange chromosomes
  • is required for CDC20 to form a complex with BUB1B
  • might play an important role in the development of gastric cancer and silencing the MAD2L1 gene may help to deal with the multidrug resistance of gastric cancer cells
  • MAD2L1-containing complexes are removed in stages during mitotic progression
  • possible differential regulation of different MAD2L1-containing complexes during checkpoint inactivation
  • its overexpression is a critical mediator of the chromosome instability observed upon inactivation of two major tumor suppressor pathways
  • new function for MAD2L1 to stabilize kinetochore-microtubule (k-MT) attachments independent of the checkpoint
  • CHEK1 and MAD2L1 crosstalk in the DNA damage checkpoint and in the mitotic spindle checkpoint
  • in response to DNA damage, MAD2L1 and the histone variant CENPA become enriched at the nuclear periphery in a DNA damage response (DDR)-dependent manner
  • is one of the key components of the spindle and mitotic checkpoint complex that regulates the fidelity of cell division along with MAD1L1, CDC20, BUB1B
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    text necessary component of the mitotic checkpoint
    PATHWAY
    metabolism
    signaling
    a component . component of the mitotic spindle assembly checkpoint
  • component of the SAC and form an heterodimer with MAD1L1 at the nuclear pore complex as a cell enters mitosis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associating with the anaphase promoting complex (APC), thereby inhibiting its ubiquitin ligase activity
  • ADAM17
  • PCID2 is essential for B cell survival through the regulation of MAD2L1 expression during B cell differentiation
  • although MAD2L1BP binds to MAD2L1, it promotes the dissociation of CDC20 from BUB1B in MCC
  • interacting with MAD1L1 (recruitment of the spindle-assembly checkpoint protein MAD2L1, through MAD1L1, to non-bioriented kinetochores is needed to stop cell-cycle progression)
  • interacting with CDC20 (key event during spindle assembly checkpoint activation)
  • CHFR interact with MAD2L1, an important component of the spindle assembly checkpoint, where CHFR knockdown resulted in mislocalization of MAD2L1 and disruption of the MAD2L1/CDC20 interaction
  • direct interaction between BUB1B and MAD2L1 and the interaction plays critical roles in mitotic checkpoint complex-mediated inhibition of anaphase-promoting complex/cyclosome (APC/C)
  • SGOL2 specifically interacts with MAD2L1 in a manner that strongly resembles the interactions of MAD2L1 with MAD1L1 or CDC20
  • binding of MAD2L1BP to MAD2L1 in mitotic checkpoint complex (MCC) may trigger a conformational change in CDC20 that facilitates its phosphorylation by CDK, and the latter process may promote its dissociation from BUB1B
  • MAD2L1 competes directly for CDC20 with the anaphase-promoting complex/cyclosome (APC/C), which would contribute to the rapid and potent inhibition of CDC20
  • stable interaction of CDC20 with MAD2 is required to maintain spindle assembly checkpoint (SAC) signaling
  • promotes efficient mitotic exit, specifically the metaphase-anaphase transition, by antagonizing MAD2L1 function
  • TPR is required for normal SAC response by stabilizing MAD1L1 and MAD2L2 before mitosis
  • MAD2L1BP is an antagonist of the SAC effector MAD2L1 and promotes silencing of the SAC and mitotic progression
  • CHEK1 is required for the metaphase-anaphase transition via regulating the subcellular localization and the expression of CDC20 and MAD2L1
  • WT1 regulates the mitotic checkpoint complex (MCC) by directly interacting with the spindle assembly checkpoint protein, MAD2L1
  • UBD play a role in mitotic regulation through its interaction with mitotic arrest-deficient 2 (MAD2L1)
  • interaction of UBD with MAD2L1 is a key mechanism underlying the promalignant property of UBD and offer prospects for the development of anticancer strategies
  • MAD2L1BP is a MAD2L1-interacting protein that serves as a spindle checkpoint silencer at mitosis
  • MAD1L1 plays a minor role in influencing the MAD2L1-dependent regulation of AURKB suggesting that the effects of MAD2L1 on AURKB are independent of the spindle checkpoint complex
  • unexpected dependency on TRIP13 in cells overexpressing MAD2L1
  • TRIP13 regulates both MAD2L1 and meiotic HORMAD1, HORMAD2 by disassembling these HORMA domain-closure motif complexes
  • TRIP13-MAD2L1BP intercepts and disassembles free MCC not bound to anaphase-promoting complex/cyclosome (APC/C) through mediating the local unfolding of the MAD2L1 C-terminal region
  • cell & other
    REGULATION
    repressed by by TP53 and its upregulation is required for chromosome instability in a TP53 mutant tumor model
    Other phosphorylation regulates its conformational transition and might contribute to checkpoint inactivation through differentially regulating MAD2L1 binding to MAD1L1 and CDC20
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in maternal age-related aneuploidy
    tumoral     --over  
    in ductal breast carcinoma
    constitutional       loss of function
    loss of spindle assembly checkpoint proteins, such as BUB1 and MAD2L1, may cause spontaneous miscarriages
    constitutional     --low  
    reduced MAD2L1 levels attenuate the apoptotic response to mis-segregating sex chromosomes and allow the formation of aneuploid sperm
    tumoral     --over  
    of CDC20 and MAD2L1 is related to poor prognosis of urothelial bladder cancer
    Susceptibility to lung cancer
    Variant & Polymorphism other genetic variants in MAD2L1 confer susceptibility to lung cancer, which might result from reduced spindle checkpoint function due to attenuated function of MAD2L1
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS