Human Gene MAD2L2 (uc001asp.3)
  Description: Homo sapiens MAD2 mitotic arrest deficient-like 2 (yeast) (MAD2L2), transcript variant 2, mRNA.
RefSeq Summary (NM_006341): The protein encoded by this gene 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. The encoded protein, which is similar to MAD2L1, is capable of interacting with ADAM9, ADAM15, REV1, and REV3 proteins. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr1:11,734,537-11,741,495 Size: 6,959 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg19 chr1:11,734,832-11,740,658 Size: 5,827 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:11,734,537-11,741,495)mRNA (may differ from genome)Protein (211 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: MD2L2_HUMAN
DESCRIPTION: RecName: Full=Mitotic spindle assembly checkpoint protein MAD2B; AltName: Full=Mitotic arrest deficient 2-like protein 2; Short=MAD2-like protein 2; AltName: Full=REV7 homolog; Short=hREV7;
FUNCTION: Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation.
SUBUNIT: Homooligomer (Probable). Interacts with REV1. Interacts with ADAM9. Interacts with CHAMP1. Interacts with REV3L. Interacts with FZR1 (in complex with the anaphase promoting complex APC). Interacts with CDC20; PubMed:11459825 could not detect the interaction. Interacts with RAN. Interacts with ELK1; the interaction is direct and recruits MAD2L2 to ELK1-specific promoters. May interact with the JNK kinases MAPK8 and/or MAPK9 to stimulate ELK1 phosphorylation and transcriptional activity upon DNA damage. Interacts with TCF7L2; prevents its binding to promoters and negatively modulates its transcriptional activity. Interacts with YY1AP1. Interacts with S.flexneri protein ipaB; prevents the interaction of MAD2L2 with FZR1 and CDC20 resulting in an activation of the anaphase-promoting complex APC and a cell cycle arrest. Interacts with PRCC; the interaction is direct. Interacts with POGZ.
INTERACTION: Q13443:ADAM9; NbExp=3; IntAct=EBI-77889, EBI-77903; Q12834:CDC20; NbExp=2; IntAct=EBI-77889, EBI-367462; P30260:CDC27; NbExp=2; IntAct=EBI-77889, EBI-994813; Q9UM11:FZR1; NbExp=2; IntAct=EBI-77889, EBI-724997; P18011:ipaB (xeno); NbExp=7; IntAct=EBI-77889, EBI-490239;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton, spindle. Cytoplasm.
TISSUE SPECIFICITY: Ubiquitously expressed.
SIMILARITY: Contains 1 HORMA domain.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mad2l2/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MAD2L2
CDC HuGE Published Literature: MAD2L2

-  MalaCards Disease Associations
  MalaCards Gene Search: MAD2L2
Diseases sorted by gene-association score: fanconi anemia, complementation group v* (1280), fanconi anemia, complementation group a* (77), ovarian clear cell carcinoma (7), diabetic encephalopathy (6), renal cell carcinoma (2), renal cell carcinoma, papillary (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 32.34 RPKM in Testis
Total median expression: 416.91 RPKM



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

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -220.10412-0.534 Picture PostScript Text
3' UTR -123.60295-0.419 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
3ABD - X-ray MuPIT 3ABE - X-ray MuPIT 3VU7 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9UI95
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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 orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001102 RNA polymerase II activating transcription factor binding
GO:0005515 protein binding
GO:0008432 JUN kinase binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001558 regulation of cell growth
GO:0006281 DNA repair
GO:0006302 double-strand break repair
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006974 cellular response to DNA damage stimulus
GO:0007015 actin filament organization
GO:0007049 cell cycle
GO:0007094 mitotic spindle assembly checkpoint
GO:0010719 negative regulation of epithelial to mesenchymal transition
GO:0010944 negative regulation of transcription by competitive promoter binding
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0042177 negative regulation of protein catabolic process
GO:0042276 error-prone translesion synthesis
GO:0042772 DNA damage response, signal transduction resulting in transcription
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0045893 positive regulation of transcription, DNA-templated
GO:0051301 cell division
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:1904667 negative regulation of ubiquitin protein ligase activity
GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin
GO:2000678 negative regulation of transcription regulatory region DNA binding

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005819 spindle
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0016035 zeta DNA polymerase complex
GO:0005680 anaphase-promoting complex


-  Descriptions from all associated GenBank mRNAs
  BC015244 - Homo sapiens MAD2 mitotic arrest deficient-like 2 (yeast), mRNA (cDNA clone MGC:17940 IMAGE:3916742), complete cds.
AF072933 - Homo sapiens Mad2-like protein mRNA, complete cds.
AF139365 - Homo sapiens Mad2B protein (MAD2B) mRNA, complete cds.
AF157482 - Homo sapiens Rev7p (REV7) mRNA, complete cds.
AK027327 - Homo sapiens cDNA FLJ14421 fis, clone HEMBA1005621, highly similar to Mitotic spindle assembly checkpoint protein MAD2B.
AK094316 - Homo sapiens cDNA FLJ36997 fis, clone BRACE2007087, highly similar to Mitotic spindle assembly checkpoint protein MAD2B.
JD467241 - Sequence 448265 from Patent EP1572962.
JD306837 - Sequence 287861 from Patent EP1572962.
JD095303 - Sequence 76327 from Patent EP1572962.
JD185146 - Sequence 166170 from Patent EP1572962.
JD449417 - Sequence 430441 from Patent EP1572962.
JD482295 - Sequence 463319 from Patent EP1572962.
JD445585 - Sequence 426609 from Patent EP1572962.
JD080960 - Sequence 61984 from Patent EP1572962.
JD448253 - Sequence 429277 from Patent EP1572962.
JD157533 - Sequence 138557 from Patent EP1572962.
AF080398 - Homo sapiens MAD2-like protein mRNA, complete cds.
CU677251 - Synthetic construct Homo sapiens gateway clone IMAGE:100018589 5' read MAD2L2 mRNA.
DQ891038 - Synthetic construct clone IMAGE:100003668; FLH168737.01X; RZPDo839C0894D MAD2 mitotic arrest deficient-like 2 (yeast) (MAD2L2) gene, encodes complete protein.
DQ894217 - Synthetic construct Homo sapiens clone IMAGE:100008677; FLH168733.01L; RZPDo839C0893D MAD2 mitotic arrest deficient-like 2 (yeast) (MAD2L2) gene, encodes complete protein.
DQ582520 - Homo sapiens piRNA piR-32632, complete sequence.
JD408421 - Sequence 389445 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
hsa05100 - Bacterial invasion of epithelial cells
hsa05131 - Shigellosis

Reactome (by CSHL, EBI, and GO)

Protein Q9UI95 (Reactome details) participates in the following event(s):

R-HSA-110322 Formation of Pol zeta complex
R-HSA-5652151 REV1 recruits POLZ to (AP:Cyt)-DNA Template
R-HSA-5655835 POLK forms a quaternary complex with REV1 and POLZ on damaged DNA template
R-HSA-5656105 POLI simultaneously binds REV1 and monoUb:K164-PCNA at damaged DNA
R-HSA-110311 POLZ extends translesion synthesis
R-HSA-5655965 POLK and POLZ cooperate in elongation of mispaired primer termini
R-HSA-5656158 POLZ elongates POLI-incorporated dNMP
R-HSA-5655892 POLK incorporates dNMP opposite to damaged DNA base
R-HSA-5656148 POLI incorporates dNMP opposite to damaged DNA base
R-HSA-110312 Translesion synthesis by REV1
R-HSA-5655862 Translesion synthesis by POLK
R-HSA-5656121 Translesion synthesis by POLI
R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template
R-HSA-73893 DNA Damage Bypass
R-HSA-73894 DNA Repair

-  Other Names for This Gene
  Alternate Gene Symbols: B3KNE3, MAD2B, MD2L2_HUMAN, NM_006341, NP_006332, Q5TGW7, Q9UI95, Q9UNA7, Q9Y6I6, REV7
UCSC ID: uc001asp.3
RefSeq Accession: NM_006341
Protein: Q9UI95 (aka MD2L2_HUMAN or MD22_HUMAN)
CCDS: CCDS134.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MAD2L2:
fa (Fanconi Anemia)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_006341.3
exon count: 9CDS single in 3' UTR: no RNA size: 1163
ORF size: 636CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1324.00frame shift in genome: no % Coverage: 96.22
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
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.