ID:MD2L1_HUMAN DESCRIPTION: RecName: Full=Mitotic spindle assembly checkpoint protein MAD2A; Short=HsMAD2; AltName: Full=Mitotic arrest deficient 2-like protein 1; Short=MAD2-like protein 1; FUNCTION: Component 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. SUBUNIT: Monomer 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. INTERACTION: P78536:ADAM17; NbExp=3; IntAct=EBI-78203, EBI-78188; Q12834:CDC20; NbExp=5; IntAct=EBI-78203, EBI-367462; Q9Y6D9:MAD1L1; NbExp=4; IntAct=EBI-78203, EBI-742610; Q15013:MAD2L1BP; NbExp=4; IntAct=EBI-78203, EBI-712181; SUBCELLULAR LOCATION: Nucleus. 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. 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. 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. SIMILARITY: Belongs to the MAD2 family. SIMILARITY: Contains 1 HORMA domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MAD2L1ID304.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13257
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
JD177415 - Sequence 158439 from Patent EP1572962. JD430255 - Sequence 411279 from Patent EP1572962. JD559685 - Sequence 540709 from Patent EP1572962. JD092522 - Sequence 73546 from Patent EP1572962. JD536209 - Sequence 517233 from Patent EP1572962. JD229759 - Sequence 210783 from Patent EP1572962. AJ000186 - Homo sapiens mRNA for MAD2 protein. BC000356 - Homo sapiens MAD2 mitotic arrest deficient-like 1 (yeast), mRNA (cDNA clone MGC:8662 IMAGE:2964388), complete cds. U31278 - Homo sapiens mitotic feedback control protein Madp2 homolog mRNA, complete cds. BC070283 - Homo sapiens MAD2 mitotic arrest deficient-like 1 (yeast), mRNA (cDNA clone MGC:88276 IMAGE:6654207), complete cds. BC005945 - Homo sapiens MAD2 mitotic arrest deficient-like 1 (yeast), mRNA (cDNA clone MGC:14577 IMAGE:4132892), complete cds. AK298228 - Homo sapiens cDNA FLJ50822 complete cds, moderately similar to Mitotic spindle assembly checkpoint protein MAD2A. U65410 - Human Mad2 (hsMAD2) mRNA, complete cds. JD225988 - Sequence 207012 from Patent EP1572962. JD167945 - Sequence 148969 from Patent EP1572962. JD324569 - Sequence 305593 from Patent EP1572962. AK223433 - Homo sapiens mRNA for MAD2-like 1 variant, clone: FCC111D09. AF394735 - Homo sapiens MAD2 mitotic arrest deficient-like 1 variant (MAD2L1) mRNA, complete cds. JD358115 - Sequence 339139 from Patent EP1572962. EU831987 - Synthetic construct Homo sapiens clone HAIB:100067016; DKFZo008H0423 MAD2 mitotic arrest deficient-like 1 (yeast) protein (MAD2L1) gene, encodes complete protein. AK313827 - Homo sapiens cDNA, FLJ94449, Homo sapiens MAD2 mitotic arrest deficient-like 1 (yeast) (MAD2L1),mRNA. KJ891565 - Synthetic construct Homo sapiens clone ccsbBroadEn_00959 MAD2L1 gene, encodes complete protein. EU832080 - Synthetic construct Homo sapiens clone HAIB:100067109; DKFZo004H0424 MAD2 mitotic arrest deficient-like 1 (yeast) protein (MAD2L1) gene, encodes complete protein. AB528692 - Synthetic construct DNA, clone: pF1KB6923, Homo sapiens MAD2L1 gene for MAD2 mitotic arrest deficient-like protein 1, without stop codon, in Flexi system. JD024684 - Sequence 5708 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q13257 (Reactome details) participates in the following event(s):
R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex R-HSA-141429 Inactivation of APC/C via CDC20 sequestration R-HSA-141437 Formation of the MCC complex R-HSA-141439 Release of activated MAD2 from kinetochores R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1 R-HSA-141423 Binding of the MCC complex to the APC/C complex R-HSA-174238 Activation of APC/C:Cdc20 by dissociation of Cdc20:phospho-APC/C from Cdc20:phospho-APC/C:Mad2:Bub3:BubR1 R-HSA-141409 Mad1 binds kinetochore R-HSA-375302 Kinetochore capture of astral microtubules R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 R-HSA-174171 Association of Cyclin A with the APC/C R-HSA-179410 Association of Nek2A with MCC:APC/C R-HSA-2467811 Separation of sister chromatids R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores R-HSA-174104 Ubiquitination of Cyclin A by APC/C:Cdc20 complex R-HSA-179417 Multiubiquitination of Nek2A R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal R-HSA-141405 Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components R-HSA-141430 Inactivation of APC/C via direct inhibition of the APC/C complex R-HSA-141424 Amplification of signal from the kinetochores R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins R-HSA-69618 Mitotic Spindle Checkpoint R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase R-HSA-68877 Mitotic Prometaphase R-HSA-5663220 RHO GTPases Activate Formins R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A R-HSA-179409 APC-Cdc20 mediated degradation of Nek2A R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins R-HSA-69620 Cell Cycle Checkpoints R-HSA-174143 APC/C-mediated degradation of cell cycle proteins R-HSA-2500257 Resolution of Sister Chromatid Cohesion R-HSA-2467813 Separation of Sister Chromatids R-HSA-68886 M Phase R-HSA-195258 RHO GTPase Effectors R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint R-HSA-1640170 Cell Cycle R-HSA-453276 Regulation of mitotic cell cycle R-HSA-68882 Mitotic Anaphase R-HSA-69278 Cell Cycle (Mitotic) R-HSA-194315 Signaling by Rho GTPases R-HSA-2555396 Mitotic Metaphase and Anaphase R-HSA-162582 Signal Transduction
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
