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Protein

Mitotic spindle assembly checkpoint protein MAD2A

Gene

Mad2l1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

GO - Molecular functioni

  1. identical protein binding Source: MGI
  2. protein homodimerization activity Source: MGI

GO - Biological processi

  1. cell division Source: UniProtKB-KW
  2. mitotic cell cycle checkpoint Source: MGI
  3. mitotic sister chromatid segregation Source: MGI
  4. mitotic spindle assembly checkpoint Source: MGI
  5. negative regulation of APC-Cdc20 complex activity Source: MGI
  6. negative regulation of apoptotic process Source: UniProtKB
  7. negative regulation of mitotic cell cycle Source: MGI
  8. negative regulation of mitotic metaphase/anaphase transition Source: MGI
  9. negative regulation of protein catabolic process Source: UniProtKB
  10. positive regulation of mitotic cell cycle spindle assembly checkpoint Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Enzyme and pathway databases

ReactomeiREACT_293797. APC-Cdc20 mediated degradation of Nek2A.
REACT_297400. Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
REACT_303340. Inactivation of APC/C via direct inhibition of the APC/C complex.
REACT_305159. Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components.
REACT_306375. Mitotic Prometaphase.
REACT_321346. Separation of Sister Chromatids.
REACT_329805. Resolution of Sister Chromatid Cohesion.
REACT_333554. APC/C:Cdc20 mediated degradation of mitotic proteins.
REACT_336745. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitotic spindle assembly checkpoint protein MAD2A
Alternative name(s):
Mitotic arrest deficient 2-like protein 1
Short name:
MAD2-like protein 1
Gene namesi
Name:Mad2l1
Synonyms:Mad2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1860374. Mad2l1.

Subcellular locationi

  1. Nucleus By similarity
  2. Chromosomecentromerekinetochore By similarity
  3. Cytoplasm By similarity
  4. Cytoplasmcytoskeletonspindle pole By similarity

  5. Note: Recruited by MAD1L1 to unattached kinetochores (By similarity). Recruited to the nuclear pore complex by TPR during interphase (By similarity). Recruited to kinetochores in late prometaphase after BUB1, CENPF, BUB1B and CENPE. Kinetochore association requires the presence of NEK2 (By similarity).By similarity

GO - Cellular componenti

  1. chromosome, centromeric region Source: MGI
  2. condensed chromosome kinetochore Source: UniProtKB-SubCell
  3. cytoplasm Source: MGI
  4. cytosol Source: UniProtKB
  5. kinetochore Source: MGI
  6. mitotic spindle Source: UniProtKB
  7. nuclear pore Source: Ensembl
  8. nucleus Source: UniProtKB
  9. perinuclear region of cytoplasm Source: UniProtKB
  10. spindle pole Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 205204Mitotic spindle assembly checkpoint protein MAD2APRO_0000126118Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei170 – 1701PhosphoserineBy similarity
Modified residuei195 – 1951PhosphoserineBy similarity

Post-translational modificationi

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 (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ9Z1B5.
PaxDbiQ9Z1B5.
PRIDEiQ9Z1B5.

PTM databases

PhosphoSiteiQ9Z1B5.

Expressioni

Gene expression databases

BgeeiQ9Z1B5.
ExpressionAtlasiQ9Z1B5. baseline and differential.
GenevestigatoriQ9Z1B5.

Interactioni

Subunit structurei

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. Kinetochore association is repressed by UBD (By similarity). Interacts with NEK2 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Sgol2Q7TSY83EBI-2552918,EBI-2552468

Protein-protein interaction databases

BioGridi207818. 31 interactions.
IntActiQ9Z1B5. 30 interactions.
MINTiMINT-123716.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1B5.
SMRiQ9Z1B5. Positions 11-205.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 197184HORMAPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni195 – 20511Required for assuming the closed conformation and for interaction with CDC20By similarityAdd
BLAST

Domaini

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 (By similarity).By similarity

Sequence similaritiesi

Belongs to the MAD2 family.Curated
Contains 1 HORMA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG263853.
GeneTreeiENSGT00390000007908.
HOGENOMiHOG000199586.
HOVERGENiHBG105691.
InParanoidiQ9Z1B5.
KOiK02537.
OMAiSIHKVNS.
OrthoDBiEOG7288SG.
PhylomeDBiQ9Z1B5.
TreeFamiTF101084.

Family and domain databases

Gene3Di3.30.900.10. 1 hit.
InterProiIPR003511. HORMA_DNA-bd.
IPR027097. Mad2.
[Graphical view]
PANTHERiPTHR11842:SF11. PTHR11842:SF11. 1 hit.
PfamiPF02301. HORMA. 1 hit.
[Graphical view]
SUPFAMiSSF56019. SSF56019. 1 hit.
PROSITEiPS50815. HORMA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9Z1B5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAQQLAREQG ITLRGSAEIV AEFFSFGINS ILYQRGIYPS ETFTRVQKYG
60 70 80 90 100
LTLLTTTDPE LIKYLNNVVE QLKEWLYKCS VQKLVVVISN IESGEVLERW
110 120 130 140 150
QFDIECDKTA KEEGVRREKS QKAIQDEIRS VIRQITATVT FLPLLEVSCS
160 170 180 190 200
FDLLIYTDKD LVVPEKWEES GPQFITNCEE VRLRSFTTTI HKVNSMVAYK

TPVND
Length:205
Mass (Da):23,598
Last modified:January 11, 2001 - v2
Checksum:iA9F3F28BC4C9738E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti157 – 1571T → A in AAD09238 (Ref. 1) Curated
Sequence conflicti178 – 1781C → S in AAD09238 (Ref. 1) Curated
Sequence conflicti201 – 2011T → I in AAD09238 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83902 mRNA. Translation: AAD09238.1.
AF261919 Genomic DNA. Translation: AAF69525.1.
AK082934 mRNA. Translation: BAC38700.1.
CCDSiCCDS20210.1.
RefSeqiNP_062372.2. NM_019499.4.
XP_006506469.1. XM_006506406.2.
UniGeneiMm.489653.

Genome annotation databases

EnsembliENSMUST00000101343; ENSMUSP00000098897; ENSMUSG00000029910.
ENSMUST00000116605; ENSMUSP00000112304; ENSMUSG00000029910.
GeneIDi56150.
KEGGimmu:56150.
UCSCiuc009cen.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83902 mRNA. Translation: AAD09238.1.
AF261919 Genomic DNA. Translation: AAF69525.1.
AK082934 mRNA. Translation: BAC38700.1.
CCDSiCCDS20210.1.
RefSeqiNP_062372.2. NM_019499.4.
XP_006506469.1. XM_006506406.2.
UniGeneiMm.489653.

3D structure databases

ProteinModelPortaliQ9Z1B5.
SMRiQ9Z1B5. Positions 11-205.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207818. 31 interactions.
IntActiQ9Z1B5. 30 interactions.
MINTiMINT-123716.

PTM databases

PhosphoSiteiQ9Z1B5.

Proteomic databases

MaxQBiQ9Z1B5.
PaxDbiQ9Z1B5.
PRIDEiQ9Z1B5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000101343; ENSMUSP00000098897; ENSMUSG00000029910.
ENSMUST00000116605; ENSMUSP00000112304; ENSMUSG00000029910.
GeneIDi56150.
KEGGimmu:56150.
UCSCiuc009cen.1. mouse.

Organism-specific databases

CTDi4085.
MGIiMGI:1860374. Mad2l1.

Phylogenomic databases

eggNOGiNOG263853.
GeneTreeiENSGT00390000007908.
HOGENOMiHOG000199586.
HOVERGENiHBG105691.
InParanoidiQ9Z1B5.
KOiK02537.
OMAiSIHKVNS.
OrthoDBiEOG7288SG.
PhylomeDBiQ9Z1B5.
TreeFamiTF101084.

Enzyme and pathway databases

ReactomeiREACT_293797. APC-Cdc20 mediated degradation of Nek2A.
REACT_297400. Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
REACT_303340. Inactivation of APC/C via direct inhibition of the APC/C complex.
REACT_305159. Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components.
REACT_306375. Mitotic Prometaphase.
REACT_321346. Separation of Sister Chromatids.
REACT_329805. Resolution of Sister Chromatid Cohesion.
REACT_333554. APC/C:Cdc20 mediated degradation of mitotic proteins.
REACT_336745. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.

Miscellaneous databases

NextBioi311932.
PROiQ9Z1B5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Z1B5.
ExpressionAtlasiQ9Z1B5. baseline and differential.
GenevestigatoriQ9Z1B5.

Family and domain databases

Gene3Di3.30.900.10. 1 hit.
InterProiIPR003511. HORMA_DNA-bd.
IPR027097. Mad2.
[Graphical view]
PANTHERiPTHR11842:SF11. PTHR11842:SF11. 1 hit.
PfamiPF02301. HORMA. 1 hit.
[Graphical view]
SUPFAMiSSF56019. SSF56019. 1 hit.
PROSITEiPS50815. HORMA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a novel component of the spindle assembly checkpoint in mammalian cells."
    Jin D.-Y., Jeang K.-T.
    Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
    Tissue: Embryo.
  2. "Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2."
    Dobles M., Liberal V., Scott M.L., Benezra R., Sorger P.K.
    Cell 101:635-645(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.

Entry informationi

Entry nameiMD2L1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1B5
Secondary accession number(s): Q9JI53
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: January 11, 2001
Last modified: April 1, 2015
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.