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mitotic spindle assembly checkpoint protein MAD2A; HsMAD2; mitotic arrest deficient 2-like protein 1; MAD2-like protein 1 (MAD2L1, MAD2)

Function: - component of the spindle-assembly checkpoint - required for execution of the which monitors the process of kinetochore-spindle attachment & inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate - phosphorylated on multiple Ser - phosphorylation varies during the cell cycle & is highest during mitosis - phosphorylation abolishes interaction with MAD1L1 & reduces interaction with CDC20 - monomer & homodimer - heterotetramer with MAD1L1 - formation of a heterotetrameric core complex containing 2 molecules each of MAD1L1 & of MAD2L1 promotes binding of another molecule of MAD2L1 to each MAD2L1, resulting in a heterohexamer - interacts with CDC20, MAD2L1BP & with ADAM17/TACE - dimeric MAD2L1 in the closed conformation interacts with CDC20 - monomeric MAD2L1 in the open conformation does not interact with CDC20 - CDC20 competes with MAD1L1 for MAD2L1 binding - interacts with TPR - binds to UBD during mitosis Structure: - the protein has two highly different native conformations, a) an inactive open conformation that cannot bind CDC20 & that predominates in cytosolic monomers b) 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 2 molecules of MAD1L1 & of MAD2L1 in the closed conformation promotes binding of another molecule of MAD2L1 in the open conformation & the conversion of the open to the closed form, & thereby promotes interaction with CDC20 - belongs to the MAD2 family - contains 1 HORMA domain Compartment: - nucleus, kinetochore, cytoplasm - 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 & CENPE - kinetochore association requires the presence of NEK2 - kinetochore association is repressed by UBD

General

nuclear protein phosphoprotein

Properties

SIZE: entity length = 205 aa MW = 24 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl HORMA {14-197} MOTIF: Ser phosphorylation site {S170} Ser phosphorylation site {S178} conformation & CDC20 interaction {195-205} MOTIF: Ser phosphorylation site {S195}

Database Correlations

OMIM 601467 UniProt Q13257 Pfam PF02301 Entrez Gene 4085 Kegg hsa:4085

References

  1. UniProt :accession Q13257
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/MAD2L1ID304.html