Human Gene MAD2L1 (uc003idl.2) Description and Page Index
Description: Homo sapiens MAD2 mitotic arrest deficient-like 1 (yeast) (MAD2L1), mRNA. RefSeq Summary (NM_002358): MAD2L1 is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. MAD2L1 is related to the MAD2L2 gene located on chromosome 1. A MAD2 pseudogene has been mapped to chromosome 14. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1660805.257712.1, SRR5189661.86000.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000296509.11/ ENSP00000296509.5 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END## Transcript (Including UTRs) Position: hg19 chr4:120,980,579-120,988,013 Size: 7,435 Total Exon Count: 5 Strand: - Coding Region Position: hg19 chr4:120,981,273-120,987,889 Size: 6,617 Coding Exon Count: 5
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";
Genetic Association Studies of Complex Diseases and Disorders
Dehydroepiandrosterone Shih-Jen Hwang et al. BMC medical genetics 2007, A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study., BMC medical genetics.
Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified.
Echocardiography Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics.
In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
Electrocardiography Christopher Newton-Cheh et al. BMC medical genetics 2007, Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study., BMC medical genetics.
In the community-based Framingham Heart Study none of the ECG and HRV results individually attained genomewide significance. However, the presence of bona fide QT-associated SNPs among the top 117 results for QT duration supports the importance of efforts to validate top results from the reported scans. Finding genetic variants associated with ECG and HRV quantitative traits may identify novel genes and pathways implicated in arrhythmogenesis and allow for improved recognition of individuals at high risk for arrhythmias in the general population.
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.