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FLASH GENE
Symbol MAD2L2 contributors: mct/npt - updated : 31-05-2015
HGNC name MAD2 mitotic arrest deficient-like 2 (yeast)
HGNC id 6764
Corresponding disease
FANCV Fanconi anemia, complementation group V
Location 1p36.22      Physical location : 11.734.537 - 11.751.678
Synonym name
  • mitotic arrest deficient homolog-like 2
  • MAD2-like 2
  • mitotic spindle assembly checkpoint protein MAD2B
  • MAD2 homolog
    • Synonym symbol(s) MAD2B, REV7, POLZ2
    DNA
    TYPE functioning gene
    STRUCTURE 6.66 kb     9 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text Variants 1 and 2 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1196 24.3 211 - 2009 1944365
    9 - 1163 24.3 211 - 2009 1944365
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Urinarykidneynephronrenal capsuleglomerulus  Homo sapiens
     kidneytubule    Homo sapiens
    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
    intraspecies homolog to MAD2L1
    Homologene
    FAMILY
  • MAD family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,centromere
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • REV3L and MAD2L2 show an unexpected increase in expression during G(2)/M phase, but they localize independently in mitotic cells
    • basic FUNCTION
  • preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate
  • has a widespread role in coordinating the cellular response to DNA damage (Zhang 2007)
  • involved in TCF7L2-mediated epithelial-mesenchymal transdifferentiation (Hong 2009)
  • blocks TCF7L2-mediated transactivation (interactions abolished the DNA binding ability of TCF7L2)(Hong 2009)
  • REV1, REV3L and MAD2L2 play important roles in translesion DNA synthesis (TLS) in which DNA replication bypasses blocking lesions (pMID: 21926160)
  • MAD2L2 may mediate SIM2 function during development in CNS and thereby play a critical role in pathophysiological mechanisms in Down syndrome
  • REV1, REV3L, and MAD2L2 are pivotal proteins in translesion DNA synthesis, which allows DNA synthesis even in the presence of DNA damage
  • function of MAD2L2 is essential in primordial germ cells (PGCs), and thus of high relevance for fertility
  • is indispensible for mitotic checkpoint control and DNA repair
  • role in the FA-BRCA pathway and DNA interstrand crosslink (ICL) repair
  • is a necessary downstream effector of the FA-BRCA pathway, most likely functioning in the translesion DNA synthesis step of ICL repair
  • important epigenetic function of MAD2L2, a protein originally known for its role in DNA damage repair, and for its requirement in germ cell development
  • important function of MAD2L2 for the open chromatin configuration of ESCs
    • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the mitotic spindle assembly checkpoint
  • key component of a surveillance system that delays anaphase until all chromosomes are correctly oriented (Rimkus 2007)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associating with the anaphase promoting complex (APC), thereby inhibiting its ubiquitin ligase activity
  • REV3, ADAM9 (MDC9)
  • interaction partner for ELK1 (MAD2L2 acts to promote ELK1 phosphorylation by the c-Jun N-terminal protein kinase (JNK) MAP kinases) (Zhang 2007)
  • YY1AP1-interacting protein, is MAD2L2
  • interacts with TCF7L2 (is a TCF7L2-binding protein, and interaction abolished the DNA binding ability of TCF7L2) (Hong 2009)
  • RAN is a novel MAD2L2 binding protein (protein-protein interaction may play a role in the control over the spindle checkpoint during mitosis andin the regulation of nucleocytoplasmic trafficking during interphase
  • modulates expression of SNAI2, a TCF4-beta-catenin-inducible gene, and E-cadherin, a downstream target gene of SNAI2 (Hong 2009)
  • interacts with CLTA during the G2/M phase of the cell cycle and depletion of MAD2l2 leads to a marked increase in the percentage of misaligned chromosomes and a redistribution of CLTA during mitosis (pMID: 21152103)
  • MAD2L2 is a novel SIM2 binding protein
  • role of MAD2L2 in governing REV1 stability and interplay between translesion DNA synthesis (TLS) and anaphase-promoting complex (APC)-dependent proteolysis
  • MAD2L2 helps to ensure a robustly bistable switch between APC/C(CDC20) and APC/C(CDH1) during the metaphase-to-anaphase transition, thereby contributing to mitotic fidelity
  • MAD2L2 has a profibrotic role during fibroblast activation and tubulointerstitial fibrosis (TIF) by suppressing SKIL expression
  • stabilize and enhance the polymerase activity of the catalytic subunit, REV3L
  • MAD2L2 promotes open chromatin in embryonic stem cells and derepresses the DPPA3 Locus
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) FANCV
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in cancer cells (causing premature anaphase and chromosome instability)
    tumoral     --over  
    in locally restricted colorectal tumors (Rimkus 2007)
    tumoral     --over  
    in colorectal cancer with bad prognosis (Rimkus 2007)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • murine hematopoietic stems cells (HSC) deficient in Rev7 exhibited impaired colony forming ability and increased differentiation, similar to Fancg-deficient HSCs