MAD2L1
Domain
The protein has two highly different native conformations, an inactive open conformation that cannot bind CDC20 and that predominates in cytosolic monomers, and an active closed conformation. The protein in the closed conformation preferentially dimerizes with another molecule in the open conformation, but can also form a dimer with a molecule in the closed conformation. Formation of a heterotetrameric core complex containing two molecules of MAD1L1 and of MAD2L1 in the closed conformation promotes binding of another molecule of MAD2L1 in the open conformation and the conversion of the open to the closed form, and thereby promotes interaction with CDC20.
Function
Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:15024386, PubMed:29162720). In the closed conformation (C-MAD2) forms a heterotetrameric complex with MAD1L1 at unattached kinetochores during prometaphase, the complex recruits open conformation molecules of MAD2L1 (O-MAD2) and then promotes the conversion of O-MAD2 to C-MAD2 (PubMed:29162720). Required for the execution of the mitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate (PubMed:10700282, PubMed:11804586, PubMed:15024386).
Post-translational modifications
Phosphorylated on multiple serine residues. The level of phosphorylation varies during the cell cycle and is highest during mitosis. Phosphorylation abolishes interaction with MAD1L1 and reduces interaction with CDC20. Phosphorylated by NEK2.
Sequence Similarities
Belongs to the MAD2 family.
Cellular localization
- Nucleus
- Chromosome
- Centromere
- Kinetochore
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Spindle pole
- Recruited by MAD1L1 to unattached kinetochores (Probable). Recruited to the nuclear pore complex by TPR during interphase. Recruited to kinetochores in late prometaphase after BUB1, CENPF, BUB1B and CENPE. Kinetochore association requires the presence of NEK2. Kinetochore association is repressed by UBD. Sequestered to the cytoplasm upon interaction with isoform 3 of MAD1L1 (PubMed:19010891).
Alternative names
MAD2, MAD2L1, Mitotic spindle assembly checkpoint protein MAD2A, HsMAD2, Mitotic arrest deficient 2-like protein 1, MAD2-like protein 1