UniProt functional annotation for Q13257



	UniProt functional annotation for Q13257

UniProt code: Q13257.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:29162720, PubMed:15024386). 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). {ECO:0000269|PubMed:10700282, ECO:0000269|PubMed:11804586, ECO:0000269|PubMed:15024386, ECO:0000269|PubMed:29162720}.

Subunit: Monomer and homodimer (PubMed:18022367, PubMed:18318601). Heterodimerizes with MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1 core complex (PubMed:12574116, PubMed:18981471, PubMed:12006501, PubMed:15024386). In the closed and open conformation, interacts with MAD1L1 (PubMed:29162720). 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 (PubMed:12006501). Interacts with MAD2L1BP (PubMed:12456649, PubMed:18022368). Interacts with ADAM17/TACE (PubMed:10527948). Interacts with CDC20 (PubMed:9637688, PubMed:12574116, PubMed:18981471, PubMed:10700282). Dimeric MAD2L1 in the closed conformation interacts with CDC20 (PubMed:29162720). Monomeric MAD2L1 in the open conformation does not interact with CDC20 (PubMed:11804586). CDC20 competes with MAD1L1 for MAD2L1 binding (PubMed:11804586). In the closed conformation, interacts with BUB1B (PubMed:29162720). Interacts with TTK (PubMed:29162720). Interacts with TPR (PubMed:18981471). Binds to UBD (via ubiquitin-like 1 domain) during mitosis (PubMed:16495226, PubMed:25422469). Interacts with isoform 1 and isoform 2 of NEK2 (PubMed:20034488). Interacts with HSF1; this interaction occurs in mitosis (PubMed:18794143). Interacts with isoform 3 of MAD1L1; this interaction leads to the cytoplasmic sequestration of MAD2L1 (PubMed:19010891). {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:18794143, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19010891, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:25422469, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:9637688}.

Subcellular location: Nucleus {ECO:0000269|PubMed:19010891}. Chromosome, centromere, kinetochore. Cytoplasm {ECO:0000269|PubMed:19010891}. 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. Sequestered to the cytoplasm upon interaction with isoform 3 of MAD1L1 (PubMed:19010891). {ECO:0000269|PubMed:19010891, ECO:0000305}.

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. {ECO:0000269|PubMed:10700282, ECO:0000269|PubMed:11804586, ECO:0000269|PubMed:12006501, ECO:0000269|PubMed:15024386, ECO:0000269|PubMed:18318601}.

Ptm: 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. {ECO:0000269|PubMed:12574116, ECO:0000269|PubMed:20034488}.

Similarity: Belongs to the MAD2 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:29162720, PubMed:15024386). 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). {ECO:0000269\|PubMed:10700282, ECO:0000269\|PubMed:11804586, ECO:0000269\|PubMed:15024386, ECO:0000269\|PubMed:29162720}.


Subunit:		Monomer and homodimer (PubMed:18022367, PubMed:18318601). Heterodimerizes with MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1 core complex (PubMed:12574116, PubMed:18981471, PubMed:12006501, PubMed:15024386). In the closed and open conformation, interacts with MAD1L1 (PubMed:29162720). 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 (PubMed:12006501). Interacts with MAD2L1BP (PubMed:12456649, PubMed:18022368). Interacts with ADAM17/TACE (PubMed:10527948). Interacts with CDC20 (PubMed:9637688, PubMed:12574116, PubMed:18981471, PubMed:10700282). Dimeric MAD2L1 in the closed conformation interacts with CDC20 (PubMed:29162720). Monomeric MAD2L1 in the open conformation does not interact with CDC20 (PubMed:11804586). CDC20 competes with MAD1L1 for MAD2L1 binding (PubMed:11804586). In the closed conformation, interacts with BUB1B (PubMed:29162720). Interacts with TTK (PubMed:29162720). Interacts with TPR (PubMed:18981471). Binds to UBD (via ubiquitin-like 1 domain) during mitosis (PubMed:16495226, PubMed:25422469). Interacts with isoform 1 and isoform 2 of NEK2 (PubMed:20034488). Interacts with HSF1; this interaction occurs in mitosis (PubMed:18794143). Interacts with isoform 3 of MAD1L1; this interaction leads to the cytoplasmic sequestration of MAD2L1 (PubMed:19010891). {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:18794143, ECO:0000269\|PubMed:18981471, ECO:0000269\|PubMed:19010891, ECO:0000269\|PubMed:20034488, ECO:0000269\|PubMed:25422469, ECO:0000269\|PubMed:29162720, ECO:0000269\|PubMed:9637688}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:19010891}. Chromosome, centromere, kinetochore. Cytoplasm {ECO:0000269\|PubMed:19010891}. 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. Sequestered to the cytoplasm upon interaction with isoform 3 of MAD1L1 (PubMed:19010891). {ECO:0000269\|PubMed:19010891, ECO:0000305}.
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. {ECO:0000269\|PubMed:10700282, ECO:0000269\|PubMed:11804586, ECO:0000269\|PubMed:12006501, ECO:0000269\|PubMed:15024386, ECO:0000269\|PubMed:18318601}.
Ptm:		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. {ECO:0000269\|PubMed:12574116, ECO:0000269\|PubMed:20034488}.
Similarity:		Belongs to the MAD2 family. {ECO:0000305}.