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Protein

Mitotic spindle assembly checkpoint protein MAD2A

Gene

MAD2L1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Biological processCell cycle, Cell division, Mitosis

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000164109.13
HGNCiHGNC:6763 MAD2L1
MIMi601467 gene
neXtProtiNX_Q13257

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi59256
TopDownProteomicsiQ13257-1 [Q13257-1]

PTM databases

iPTMnetiQ13257
PhosphoSitePlusiQ13257
SwissPalmiQ13257

Expressioni

Gene expression databases

BgeeiENSG00000164109 Expressed in 200 organ(s), highest expression level in secondary oocyte
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 (via ubiquitin-like 1 domain) during mitosis. Interacts with isoform 1 and isoform 2 of NEK2. Interacts with HSF1; this interaction occurs in mitosis (PubMed:18794143).16 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110260, 80 interactors
ComplexPortaliCPX-85 Mitotic spindle assembly checkpoint MAD1-MAD2 complex
CPX-88 Mitotic spindle assembly checkpoint complex MAD2
CORUMiQ13257
DIPiDIP-29653N
IntActiQ13257, 62 interactors
MINTiQ13257
STRINGi9606.ENSP00000296509

Structurei

Secondary structure

1205
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.900.10, 1 hit
InterProiView protein in InterPro
IPR003511 HORMA_dom
IPR036570 HORMA_dom_sf
IPR027097 Mad2
PANTHERiPTHR11842:SF11 PTHR11842:SF11, 1 hit
PfamiView protein in Pfam
PF02301 HORMA, 1 hit
SUPFAMiSSF56019 SSF56019, 1 hit
PROSITEiView protein in PROSITE
PS50815 HORMA, 1 hit

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RJE3D6RJE3_HUMAN
Mitotic spindle assembly checkpoint...
MAD2L1
41Annotation score:

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

Similar proteinsi

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/D/E/F/H2-205[»]
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[»]
5KHUelectron microscopy4.80T1-205[»]
5LCWelectron microscopy4.00Z1-205[»]
6F0Xelectron microscopy4.60Z1-205[»]
ProteinModelPortaliQ13257
SMRiQ13257
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110260, 80 interactors
ComplexPortaliCPX-85 Mitotic spindle assembly checkpoint MAD1-MAD2 complex
CPX-88 Mitotic spindle assembly checkpoint complex MAD2
CORUMiQ13257
DIPiDIP-29653N
IntActiQ13257, 62 interactors
MINTiQ13257
STRINGi9606.ENSP00000296509

PTM databases

iPTMnetiQ13257
PhosphoSitePlusiQ13257
SwissPalmiQ13257

Polymorphism and mutation databases

BioMutaiMAD2L1
DMDMi12230256

Proteomic databases

EPDiQ13257
MaxQBiQ13257
PaxDbiQ13257
PeptideAtlasiQ13257
PRIDEiQ13257
ProteomicsDBi59256
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
EuPathDBiHostDB:ENSG00000164109.13
GeneCardsiMAD2L1
HGNCiHGNC:6763 MAD2L1
HPAiHPA003348
MIMi601467 gene
neXtProtiNX_Q13257
OpenTargetsiENSG00000164109
PharmGKBiPA30521
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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
PROiPR:Q13257
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164109 Expressed in 200 organ(s), highest expression level in secondary oocyte
CleanExiHS_MAD2L1
ExpressionAtlasiQ13257 baseline and differential
GenevisibleiQ13257 HS

Family and domain databases

Gene3Di3.30.900.10, 1 hit
InterProiView protein in InterPro
IPR003511 HORMA_dom
IPR036570 HORMA_dom_sf
IPR027097 Mad2
PANTHERiPTHR11842:SF11 PTHR11842:SF11, 1 hit
PfamiView protein in Pfam
PF02301 HORMA, 1 hit
SUPFAMiSSF56019 SSF56019, 1 hit
PROSITEiView protein in PROSITE
PS50815 HORMA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMD2L1_HUMAN
AccessioniPrimary (citable) accession number: Q13257
Secondary accession number(s): Q53F56
, Q548X9, Q6IRW7, Q8IZX3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 185 of the entry and version 1 of the sequence. See 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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