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MGP001853

UniProt Annotations

Entry Information
Gene NameMAD2 mitotic arrest deficient-like 1 (yeast)
Protein EntryMD2L1_HUMAN
UniProt IDQ13257
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q13257-1; Sequence=Displayed; Name=2; IsoId=Q13257-2; Sequence=VSP_047644, VSP_047645;
DomainThe 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. {ECO:0000269|PubMed:10700282, ECO:0000269|PubMed:11804586, ECO:0000269|PubMed:12006501, ECO:0000269|PubMed:15024386, ECO:0000269|PubMed:18318601}.
FunctionComponent of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. 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. {ECO:0000269|PubMed:10700282, ECO:0000269|PubMed:11804586, ECO:0000269|PubMed:15024386}.
InteractionSelf; NbExp=3; IntAct=EBI-78203, EBI-78203; P78536:ADAM17; NbExp=3; IntAct=EBI-78203, EBI-78188; Q12834:CDC20; NbExp=16; IntAct=EBI-78203, EBI-367462; Q9Y6D9:MAD1L1; NbExp=11; IntAct=EBI-78203, EBI-742610; Q15013:MAD2L1BP; NbExp=7; IntAct=EBI-78203, EBI-712181; Q562F6:SGOL2; NbExp=10; IntAct=EBI-78203, EBI-989213;
PtmPhosphorylated 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. {ECO:0000269|PubMed:12574116, ECO:0000269|PubMed:20034488}.
SimilarityBelongs to the MAD2 family. {ECO:0000305}.
SimilarityContains 1 HORMA domain. {ECO:0000255|PROSITE- ProRule:PRU00109}.
Subcellular LocationNucleus. Chromosome, centromere, kinetochore. Cytoplasm. Cytoplasm, cytoskeleton, spindle pole. Note=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. {ECO:0000305}.
SubunitMonomer and homodimer. Heterotetramer with MAD1L1. Formation of a heterotetrameric core complex containing two molecules each of MAD1L1 and of MAD2L1 promotes binding of another molecule of MAD2L1 to each MAD2L1, resulting in a heterohexamer. Interacts with CDC20, MAD2L1BP and 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. Interacts with isoform 1 and isoform 2 of NEK2. {ECO:0000269|PubMed:10527948, ECO:0000269|PubMed:10700282, ECO:0000269|PubMed:11804586, ECO:0000269|PubMed:12006501, ECO:0000269|PubMed:12456649, ECO:0000269|PubMed:12574116, ECO:0000269|PubMed:15024386, ECO:0000269|PubMed:16495226, ECO:0000269|PubMed:18022367, ECO:0000269|PubMed:18022368, ECO:0000269|PubMed:18318601, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:9637688}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MAD2L1ID304.html";
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