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FLASH GENE
Symbol MAD2L1BP contributors: mct - updated : 01-06-2018
HGNC name MAD2L1 binding protein
HGNC id 21059
Location 6p21.1      Physical location : 43.597.278 - 43.608.686
Synonym name
  • caught by MAD2 protein
  • p31comet
  • Synonym symbol(s) CMT2, KIAA0110, dJ261G23.1, MGC11282, RP1-261G23.6
    DNA
    TYPE functioning gene
    STRUCTURE 11.41 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 1550 34.54 306 - 2017 28659378
    3 - 1283 31 274 - 2017 28659378
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • region of MAD2L1BP affecting interactions with MAD2L1, including the C-terminus, are essential for induction of cell death
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text located in nucleoplasm during early mitosis and in the spindle from metaphase to anaphase
    basic FUNCTION
  • may function to silence the spindle checkpoint and allow mitosis to proceed through anaphase by binding MAD2L1 after its dissociation from the MAD2L1-CD20 complex (Habu 2002)
  • exploits the two-state behavior of MAD2L1 to block its activation by acting as an "anti-MAD2L1"
  • is an essential component of the machinery that silences the checkpoint during each cell cycle
  • negatively regulates the spindle assembly checkpoint by extracting MAD2L1 from the MCC
  • is a MAD2L1-interacting protein that serves as a spindle checkpoint silencer at mitosis
  • MAD2L1BP and TRIP13 are critical for inactivating MAD2L1
  • although MAD2L1BP enhanced TRIP13-mediated MAD2L1 conversion, it was not absolutely necessary for the process
  • paradigm of the roles of MAD2L1BP and TRIP13 in both checkpoint activation and inactivation
  • CELLULAR PROCESS cell cycle, division, mitosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with MAD2L1
  • although MAD2L1BP binds to MAD2L1, it promotes the dissociation of CDC20 from BUB1B in MCC
  • 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
  • is a well-known interacting partner of the spindle assembly checkpoint (SAC) effector molecule MAD2L1
  • promotes efficient mitotic exit, specifically the metaphase-anaphase transition, by antagonizing MAD2L1 function
  • is an antagonist of the SAC effector MAD2L1 and promotes silencing of the SAC and mitotic progression
  • TRIP13, aided by the adapter protein MAD2L1BP, converts the HORMA-family spindle checkpoint protein MAD2L1 from a signaling-active 'closed' conformer to an inactive 'open' conformer
  • TRIP13, jointly with the MAD2L1BP, promotes the inactivation of the mitotic (spindle assembly) checkpoint by disassembling the mitotic checkpoint complex (MCC)
  • MAD2L1BP-induced cell death is mediated by interactions with MAD2L1 that lead to its inactivation is potentially applicable in anticancer therapy
  • MAD2L1 inhibitory protein MAD2L1BP promotes checkpoint inactivation and timely chromosome segregation
  • MAD2L1BP blocks the MAD2L1-BUB1B interaction and prevents spontaneous clathrin-mediated INSR endocytosis
  • MAD2L1BP binding to the TRIP13 N-terminal domain positions the disordered MAD2L1 N-terminus for engagement by the TRIP13 "pore loops", which in cells causes spindle assembly checkpoint defects consistent with loss of TRIP13 function
  • 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
    Other level increases during cell cycle and remains constant until late mitosis, after which it drops
    phosphorylation regulates the MAD2L1BP-MAD2 interaction to promote spindle assembly checkpoint (SAC) activity
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS