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FLASH GENE
Symbol MAD1L1 contributors: npt/mct/pgu - updated : 25-01-2016
HGNC name MAD1 mitotic arrest deficient-like 1 (yeast)
HGNC id 6762
Location 7p22.3      Physical location : 1.855.427 - 2.272.583
Synonym name
  • TAX binding protein 181
  • mitotic arrest deficiency protein 1
  • MAD1-like 1
    • Synonym symbol(s) TXBP181, PIG9, MAD1, TP53I9
    DNA
    TYPE functioning gene
    STRUCTURE 417.16 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure no TATA box
    MAPPING cloned Y linked N status provisional
    Map pter - PDGFRA - NUDT1 - FTSJ2 - MAD1L1 - PMS2 - cen
    RNA
    TRANSCRIPTS type messenger
    text all variants encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 2714 - 718 - 1999 10049595
    19 - 2717 - 718 - 1999 10049595
    19 - 2754 - 718 - 1999 10049595
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   highly
     thymus   highly
    Respiratoryrespiratory tractlarynx  highly
    Skin/Tegumentskin   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, checkpoint, M exit
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two highly conserved domains, Sin3-interacting domain (SID)
  • and basic helix-loop-helix leucine zipper domain (bHLHzip), which are essential for the function during molecular switching from proliferation to differentiation
  • C-terminal domain is a part of an extensive kinetochore-binding interface of MAD1L1, and rationalize graded kinetochore targeting of MAD1L1 during checkpoint signaling
    • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to yeast (mitotic arrest deficient) MADH1
    Homologene
    FAMILY
  • ezrin-radixin-moesin family
  • MAD1 family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,centromere
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • associated with microtubule-unattached kinetochores in mitotic cells and is a component of the spindle assembly checkpoint (SAC)
  • localise to kinetochores with BUB1B and MAD2L1
  • kinetochore localization of MAD1L1 is sufficient for a metaphase arrest that depends on MAD1L1-MAD2L1 binding
    • basic FUNCTION
  • preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate
  • playing a role in mitotic checkpoint
  • acting in a surveillance mechanism that mediates a metaphase delay in response to nonexchange chromosomes
  • involved in cell growth control and inhibition of entry into S phase until late G1
  • playing a complex role in the development of small-cell lung cancer as well as other tumors
  • required for MAD2L1 localization to kinetochores and the association of MAD2L1 with the kinetochore is a pre-requisite for its SAC functionb
  • Myc antagonist, upstream regulator of MAD2L1, that forms a tight core complex with MAD2L1 and facilitates MAD2L1 binding to Cdc20
  • plays an important role in proper mitotic progression
  • IK is a spindle pole-associated protein that colocalizes with MAD1L1 at the spindle poles in metaphase and anaphase
  • its overexpression causes aneuploidy and chromosomal instability through weakening mitotic checkpoint signaling caused by mislocalization of the MAD1L1 binding partner MAD2L1
  • MAD2L1 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, checkpoint
    cell life, differentiation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • essential component of the mitotic spindle assembly checkpoint
  • component of the SAC and form an heterodimer with MAD2L1 at the nuclear pore complex as a cell enters mitosis
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting as an homodimer with MAD2L1
  • associating and inactivating the anaphase promoting complex (APC)
  • interaction of NUP153 with the spindle assembly checkpoint protein MAD1L1 is important in the regulation of the spindle checkpoint
  • interacting with MAD2L1 (recruitment of the spindle-assembly checkpoint protein MAD2L1, through MAD1L1, to non-bioriented kinetochores is needed to stop cell-cycle progression)
  • binds to the CDH1 promoter region (regulates the expression of CDH1 and prevents cell migration)
  • CNOT3 negatively regulates the expression of MAD1L1, which is evidenced by the stabilization of MAD1L1 mRNA upon CNOT3 depletion
  • IK interacts with the human SAC protein MAD1L1
  • unexpected connection of NUP107 with the mitotic spindle assembly checkpoint protein MAD1L1
  • TPR is required for normal SAC response by stabilizing MAD1L1 and MAD2L2 before 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
  • LMO7 interacted with the spindle assembly checkpoint (SAC) protein MAD1L1
    • cell & other
    REGULATION
    activated by TP53 gain of function mutant
    Other hyperphosphorylated when PLK1 is overexpressed and that the kinase activity of PLK1 is required for MAD1L1 to locate to microtubule-unattached kinetochores
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in lung cancer and colon cancer
    tumoral     --low  
    in lung cancer and colon cancer
    tumoral   LOH    
    in breast cancer
    tumoral somatic mutation      
    in acute leukaemia
    constitutional     --over  
    its up-regulation may promote tumors and cause resistance to current therapies
    Susceptibility to lung cancer
    Variant & Polymorphism other genetic variants in MAD1L1 confer susceptibility to lung cancer, which might result from reduced spindle checkpoint function due to attenuated function of MAD1L1
    Candidate gene
    Marker
  • reduced MAD1L1 expression is a new potential diagnostic symptom of tumor metastasis
    • Therapy target
    ANIMAL & CELL MODELS