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Protein

Mitotic spindle assembly checkpoint protein MAD2A

Gene

MAD2L1

Organism
Homo sapiens (Human)
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.3 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164109-MONOMER.
ReactomeiR-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-141444. Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
R-HSA-174184. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
R-HSA-176409. APC/C:Cdc20 mediated degradation of mitotic proteins.
R-HSA-179409. APC-Cdc20 mediated degradation of Nek2A.
R-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-68877. Mitotic Prometaphase.
SIGNORiQ13257.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitotic spindle assembly checkpoint protein MAD2A
Short name:
HsMAD2
Alternative name(s):
Mitotic arrest deficient 2-like protein 1
Short name:
MAD2-like protein 1
Gene namesi
Name:MAD2L1
Synonyms:MAD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:6763. MAD2L1.

Subcellular locationi

  • Nucleus
  • Chromosomecentromerekinetochore
  • Cytoplasm
  • Cytoplasmcytoskeletonspindle 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.Curated

GO - Cellular componenti

  • condensed chromosome kinetochore Source: UniProtKB-SubCell
  • cytosol Source: UniProtKB
  • kinetochore Source: UniProtKB
  • mitotic spindle Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • spindle pole Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi13L → A: Leads to formation the closed conformation and homodimerization. 1 Publication1
Mutagenesisi75W → A: Prevents interaction with CDC20 and leads to formation of the closed conformation; when associated with A-133. 1 Publication1
Mutagenesisi133R → A: Prevents aggregation and promotes formation of monomeric protein that slowly interconverts between the open and closed conformation. 1 Publication1
Mutagenesisi153L → A: Leads to formation of the closed conformation; when associated with A-133. 1 Publication1
Mutagenesisi156Y → A: Leads to formation of the closed conformation; when associated with A-133. 1 Publication1
Mutagenesisi170S → A: Reduces phosphorylation on serine residues; when associated with A-178. Abolishes phosphorylation on serine residues; when associated with A-178 and A-195. 1 Publication1
Mutagenesisi170S → D: Abolishes interaction with MAD1L1 and reduces interaction with CDC20; when associated with D-178 and D-195. 1 Publication1
Mutagenesisi178S → A: Reduces phosphorylation on serine residues; when associated with A-170. Abolishes phosphorylation on serine residues; when associated with A-170 and A-195. 1 Publication1
Mutagenesisi178S → D: Abolishes interaction with MAD1L1 and reduces interaction with CDC20; when associated with D-170 and D-195. 1 Publication1
Mutagenesisi186F → A: Prevents formation of the closed conformation and interaction with CDC20; when associated with A-133. 1 Publication1
Mutagenesisi188T → A: Prevents formation of the closed conformation and interaction with CDC20; when associated with A-133. 1 Publication1
Mutagenesisi191H → A: Prevents formation of the closed conformation and interaction with CDC20; when associated with A-133. 1 Publication1
Mutagenesisi195S → A: Abolishes phosphorylation on serine residues; when associated with A-170 and A-178. 1 Publication1
Mutagenesisi195S → D: Abolishes interaction with MAD1L1 and reduces interaction with CDC20; when associated with D-170 and D-178. 1 Publication1
Mutagenesisi197V → A: Prevents formation of the closed conformation and interaction with CDC20; when associated with A-133. 1 Publication1
Mutagenesisi199Y → A: Prevents formation of the closed conformation and interaction with CDC20; when associated with A-133. 1 Publication1

Organism-specific databases

DisGeNETi4085.
OpenTargetsiENSG00000164109.
PharmGKBiPA30521.

Polymorphism and mutation databases

BioMutaiMAD2L1.
DMDMi12230256.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001261172 – 205Mitotic spindle assembly checkpoint protein MAD2AAdd BLAST204

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei6PhosphoserineCombined sources1
Modified residuei130PhosphoserineCombined sources1
Modified residuei170Phosphoserine1 Publication1
Modified residuei178Phosphoserine1 Publication1
Modified residuei185PhosphoserineCombined sources1
Modified residuei195PhosphoserineCombined sources1 Publication1

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 NEK2.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ13257.
MaxQBiQ13257.
PaxDbiQ13257.
PeptideAtlasiQ13257.
PRIDEiQ13257.
TopDownProteomicsiQ13257-1. [Q13257-1]

PTM databases

iPTMnetiQ13257.
PhosphoSitePlusiQ13257.
SwissPalmiQ13257.

Expressioni

Gene expression databases

BgeeiENSG00000164109.
CleanExiHS_MAD2L1.
ExpressionAtlasiQ13257. baseline and differential.
GenevisibleiQ13257. HS.

Organism-specific databases

HPAiHPA003348.

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. Interacts with isoform 1 and isoform 2 of NEK2.14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-78203,EBI-78203
ADAM17P785363EBI-78203,EBI-78188
CDC20Q1283417EBI-78203,EBI-367462
KEAP1Q141456EBI-78203,EBI-751001
MAD1L1Q9Y6D914EBI-78203,EBI-742610
MAD2L1BPQ1501311EBI-78203,EBI-712181
SDCBPO005603EBI-78203,EBI-727004
SGO2Q562F610EBI-78203,EBI-989213
TSC22D4Q9Y3Q84EBI-78203,EBI-739485

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi110260. 74 interactors.
DIPiDIP-29653N.
IntActiQ13257. 55 interactors.
MINTiMINT-108270.
STRINGi9606.ENSP00000296509.

Structurei

Secondary structure

1205
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 5Combined sources4
Beta strandi7 – 9Combined sources3
Helixi13 – 34Combined sources22
Helixi40 – 42Combined sources3
Beta strandi43 – 48Combined sources6
Beta strandi51 – 56Combined sources6
Helixi59 – 77Combined sources19
Beta strandi78 – 80Combined sources3
Beta strandi81 – 90Combined sources10
Turni91 – 93Combined sources3
Beta strandi96 – 106Combined sources11
Helixi108 – 111Combined sources4
Beta strandi116 – 118Combined sources3
Helixi121 – 139Combined sources19
Beta strandi149 – 157Combined sources9
Helixi160 – 162Combined sources3
Beta strandi167 – 169Combined sources3
Beta strandi173 – 175Combined sources3
Beta strandi177 – 182Combined sources6
Beta strandi189 – 200Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DUJNMR-A11-195[»]
1GO4X-ray2.05A/B/C/D1-205[»]
1KLQNMR-A11-205[»]
1S2HNMR-A1-205[»]
2QYFX-ray2.30A/C1-205[»]
2V64X-ray2.90A/C/F2-205[»]
D/E/H118-205[»]
2VFXX-ray1.95A/B/C/D/E/F/G/H/I/J/K/L1-205[»]
3GMHX-ray3.95A/B/C/D/E/F/G/H/I/J/K/L11-205[»]
5LCWelectron microscopy4.00Z1-205[»]
ProteinModelPortaliQ13257.
SMRiQ13257.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13257.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 197HORMAPROSITE-ProRule annotationAdd BLAST184

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni195 – 205Required for assuming the closed conformation and for interaction with CDC20Add BLAST11

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 CDC20.5 Publications

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG3285. Eukaryota.
ENOG410XSD7. LUCA.
GeneTreeiENSGT00390000007908.
HOGENOMiHOG000199586.
HOVERGENiHBG105691.
InParanoidiQ13257.
KOiK02537.
OMAiCLETNEV.
OrthoDBiEOG091G0JBM.
PhylomeDBiQ13257.
TreeFamiTF101084.

Family and domain databases

Gene3Di3.30.900.10. 1 hit.
InterProiIPR003511. HORMA_dom.
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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13257-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALQLSREQG ITLRGSAEIV AEFFSFGINS ILYQRGIYPS ETFTRVQKYG
60 70 80 90 100
LTLLVTTDLE LIKYLNNVVE QLKDWLYKCS VQKLVVVISN IESGEVLERW
110 120 130 140 150
QFDIECDKTA KDDSAPREKS QKAIQDEIRS VIRQITATVT FLPLLEVSCS
160 170 180 190 200
FDLLIYTDKD LVVPEKWEES GPQFITNSEE VRLRSFTTTI HKVNSMVAYK

IPVND
Length:205
Mass (Da):23,510
Last modified:November 1, 1996 - v1
Checksum:iB8DCBF0043836764
GO
Isoform 2 (identifier: Q13257-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     74-90: DWLYKCSVQKLVVVISN → VHPEKSLRKLSRMKSVQ
     91-205: Missing.

Show »
Length:90
Mass (Da):10,335
Checksum:i8209F5A7A7D8D09B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16S → C in BAD97153 (Ref. 8) Curated1
Sequence conflicti190I → V in AAH70283 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04764474 – 90DWLYK…VVISN → VHPEKSLRKLSRMKSVQ in isoform 2. 2 PublicationsAdd BLAST17
Alternative sequenceiVSP_04764591 – 205Missing in isoform 2. 2 PublicationsAdd BLAST115

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U65410 mRNA. Translation: AAC50781.1.
AF202273
, AF202269, AF202270, AF202271, AF202272 Genomic DNA. Translation: AAK38174.1.
U31278 mRNA. Translation: AAC52060.1.
AJ000186 mRNA. Translation: CAA03943.1.
AB056160 Genomic DNA. Translation: BAB63410.1.
AF394735 mRNA. Translation: AAN74648.1.
AK298228 mRNA. Translation: BAG60497.1.
AK313827 mRNA. Translation: BAG36562.1.
AK223433 mRNA. Translation: BAD97153.1.
AC097173 Genomic DNA. Translation: AAY40945.1.
CH471056 Genomic DNA. Translation: EAX05271.1.
CH471056 Genomic DNA. Translation: EAX05273.1.
BC000356 mRNA. Translation: AAH00356.1.
BC005945 mRNA. Translation: AAH05945.1.
BC070283 mRNA. Translation: AAH70283.1.
CCDSiCCDS3715.1. [Q13257-1]
PIRiG01942.
RefSeqiNP_002349.1. NM_002358.3. [Q13257-1]
UniGeneiHs.591697.

Genome annotation databases

EnsembliENST00000296509; ENSP00000296509; ENSG00000164109. [Q13257-1]
ENST00000333047; ENSP00000332295; ENSG00000164109. [Q13257-2]
GeneIDi4085.
KEGGihsa:4085.
UCSCiuc003idl.3. human. [Q13257-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U65410 mRNA. Translation: AAC50781.1.
AF202273
, AF202269, AF202270, AF202271, AF202272 Genomic DNA. Translation: AAK38174.1.
U31278 mRNA. Translation: AAC52060.1.
AJ000186 mRNA. Translation: CAA03943.1.
AB056160 Genomic DNA. Translation: BAB63410.1.
AF394735 mRNA. Translation: AAN74648.1.
AK298228 mRNA. Translation: BAG60497.1.
AK313827 mRNA. Translation: BAG36562.1.
AK223433 mRNA. Translation: BAD97153.1.
AC097173 Genomic DNA. Translation: AAY40945.1.
CH471056 Genomic DNA. Translation: EAX05271.1.
CH471056 Genomic DNA. Translation: EAX05273.1.
BC000356 mRNA. Translation: AAH00356.1.
BC005945 mRNA. Translation: AAH05945.1.
BC070283 mRNA. Translation: AAH70283.1.
CCDSiCCDS3715.1. [Q13257-1]
PIRiG01942.
RefSeqiNP_002349.1. NM_002358.3. [Q13257-1]
UniGeneiHs.591697.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DUJNMR-A11-195[»]
1GO4X-ray2.05A/B/C/D1-205[»]
1KLQNMR-A11-205[»]
1S2HNMR-A1-205[»]
2QYFX-ray2.30A/C1-205[»]
2V64X-ray2.90A/C/F2-205[»]
D/E/H118-205[»]
2VFXX-ray1.95A/B/C/D/E/F/G/H/I/J/K/L1-205[»]
3GMHX-ray3.95A/B/C/D/E/F/G/H/I/J/K/L11-205[»]
5LCWelectron microscopy4.00Z1-205[»]
ProteinModelPortaliQ13257.
SMRiQ13257.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110260. 74 interactors.
DIPiDIP-29653N.
IntActiQ13257. 55 interactors.
MINTiMINT-108270.
STRINGi9606.ENSP00000296509.

PTM databases

iPTMnetiQ13257.
PhosphoSitePlusiQ13257.
SwissPalmiQ13257.

Polymorphism and mutation databases

BioMutaiMAD2L1.
DMDMi12230256.

Proteomic databases

EPDiQ13257.
MaxQBiQ13257.
PaxDbiQ13257.
PeptideAtlasiQ13257.
PRIDEiQ13257.
TopDownProteomicsiQ13257-1. [Q13257-1]

Protocols and materials databases

DNASUi4085.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296509; ENSP00000296509; ENSG00000164109. [Q13257-1]
ENST00000333047; ENSP00000332295; ENSG00000164109. [Q13257-2]
GeneIDi4085.
KEGGihsa:4085.
UCSCiuc003idl.3. human. [Q13257-1]

Organism-specific databases

CTDi4085.
DisGeNETi4085.
GeneCardsiMAD2L1.
HGNCiHGNC:6763. MAD2L1.
HPAiHPA003348.
MIMi601467. gene.
neXtProtiNX_Q13257.
OpenTargetsiENSG00000164109.
PharmGKBiPA30521.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3285. Eukaryota.
ENOG410XSD7. LUCA.
GeneTreeiENSGT00390000007908.
HOGENOMiHOG000199586.
HOVERGENiHBG105691.
InParanoidiQ13257.
KOiK02537.
OMAiCLETNEV.
OrthoDBiEOG091G0JBM.
PhylomeDBiQ13257.
TreeFamiTF101084.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164109-MONOMER.
ReactomeiR-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-141444. Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
R-HSA-174184. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
R-HSA-176409. APC/C:Cdc20 mediated degradation of mitotic proteins.
R-HSA-179409. APC-Cdc20 mediated degradation of Nek2A.
R-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-5663220. RHO GTPases Activate Formins.
R-HSA-68877. Mitotic Prometaphase.
SIGNORiQ13257.

Miscellaneous databases

ChiTaRSiMAD2L1. human.
EvolutionaryTraceiQ13257.
GeneWikiiMAD2L1.
GenomeRNAii4085.
PROiQ13257.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164109.
CleanExiHS_MAD2L1.
ExpressionAtlasiQ13257. baseline and differential.
GenevisibleiQ13257. HS.

Family and domain databases

Gene3Di3.30.900.10. 1 hit.
InterProiIPR003511. HORMA_dom.
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...

Entry informationi

Entry nameiMD2L1_HUMAN
AccessioniPrimary (citable) accession number: Q13257
Secondary accession number(s): Q53F56
, Q548X9, Q6IRW7, Q8IZX3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 170 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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 one 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.