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 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:120,980,579-120,988,013)mRNA (may differ from genome)Protein (205 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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
  Genetic Association Database (archive): MAD2L1
CDC HuGE Published Literature: MAD2L1
Positive Disease Associations: Dehydroepiandrosterone , Echocardiography , Electrocardiography , Fibrinogen , Hip , HIV-1
Related Studies:
  1. 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. [PubMed 17903292]
    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.
  2. 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. [PubMed 17903301]
    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.
  3. 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. [PubMed 17903306]
    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.
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-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 16.20 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 53.84 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -41.91124-0.338 Picture PostScript Text
3' UTR -154.30694-0.222 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003511 - HORMA_DNA-bd

Pfam Domains:
PF02301 - HORMA domain

SCOP Domains:
56019 - The spindle assembly checkpoint protein mad2

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1DUJ
- NMR MuPIT

1GO4
- X-ray MuPIT

1KLQ
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
1S2H - NMR MuPIT 2QYF - X-ray MuPIT 2V64 - X-ray MuPIT
2VFX - X-ray MuPIT 3GMH - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q13257
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene Details  Gene DetailsGene DetailsGene Details
Gene Sorter  Gene SorterGene SorterGene Sorter
  EnsemblFlyBaseWormBaseSGD
  Protein SequenceProtein SequenceProtein SequenceProtein Sequence
  AlignmentAlignmentAlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity

Biological Process:
GO:0000070 mitotic sister chromatid segregation
GO:0007049 cell cycle
GO:0007093 mitotic cell cycle checkpoint
GO:0007094 mitotic spindle assembly checkpoint
GO:0031145 anaphase-promoting complex-dependent catabolic process
GO:0042177 negative regulation of protein catabolic process
GO:0043066 negative regulation of apoptotic process
GO:0045930 negative regulation of mitotic cell cycle
GO:0051301 cell division
GO:0090267 positive regulation of mitotic cell cycle spindle assembly checkpoint
GO:1904667 negative regulation of ubiquitin protein ligase activity

Cellular Component:
GO:0000775 chromosome, centromeric region
GO:0000776 kinetochore
GO:0000777 condensed chromosome kinetochore
GO:0000922 spindle pole
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0048471 perinuclear region of cytoplasm
GO:0072686 mitotic spindle
GO:0005643 nuclear pore


-  Descriptions from all associated GenBank mRNAs
  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
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04110 - Cell cycle
hsa04114 - Oocyte meiosis
hsa04914 - Progesterone-mediated oocyte maturation

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

-  Other Names for This Gene
  Alternate Gene Symbols: MAD2, MD2L1_HUMAN, NM_002358, NP_002349, Q13257, Q53F56, Q548X9, Q6IRW7
UCSC ID: uc003idl.2
RefSeq Accession: NM_002358
Protein: Q13257 (aka MD2L1_HUMAN or MD21_HUMAN)
CCDS: CCDS3715.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_002358.3
exon count: 5CDS single in 3' UTR: no RNA size: 1453
ORF size: 618CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1436.00frame shift in genome: no % Coverage: 98.83
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.