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Protein

Mitotic spindle assembly checkpoint protein MAD1

Gene

MAD1L1

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. May recruit MAD2L1 to unattached kinetochores. Has a role in the correct positioning of the septum. Required for anchoring MAD2L1 to the nuclear periphery. Binds to the TERT promoter and represses telomerase expression, possibly by interfering with MYC binding.3 Publications

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Enzyme and pathway databases

ReactomeiR-HSA-141444. Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
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.
SIGNORiQ9Y6D9.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitotic spindle assembly checkpoint protein MAD1
Alternative name(s):
Mitotic arrest deficient 1-like protein 1
Short name:
MAD1-like protein 1
Mitotic checkpoint MAD1 protein homolog
Short name:
HsMAD1
Short name:
hMAD1
Tax-binding protein 181
Gene namesi
Name:MAD1L1
Synonyms:MAD1, TXBP181
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:6762. MAD1L1.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: HPA
  • centrosome Source: UniProtKB
  • condensed chromosome kinetochore Source: UniProtKB-SubCell
  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • kinetochore Source: UniProtKB
  • mitotic spindle Source: UniProtKB
  • nucleus Source: HPA
  • spindle Source: UniProtKB
  • spindle pole Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in MAD1L1 are involved in the development and/or progression of various types of cancer.

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi8379.
MalaCardsiMAD1L1.
OpenTargetsiENSG00000002822.
PharmGKBiPA372.

Polymorphism and mutation databases

BioMutaiMAD1L1.
DMDMi52783153.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002138001 – 718Mitotic spindle assembly checkpoint protein MAD1Add BLAST718

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei16PhosphoserineCombined sources1
Modified residuei61N6-acetyllysine; alternateCombined sources1
Cross-linki61Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei214PhosphoserineCombined sources1
Modified residuei428PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated; by BUB1. Become hyperphosphorylated in late S through M phases or after mitotic spindle damage.2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Y6D9.
PaxDbiQ9Y6D9.
PeptideAtlasiQ9Y6D9.
PRIDEiQ9Y6D9.

PTM databases

iPTMnetiQ9Y6D9.
PhosphoSitePlusiQ9Y6D9.

Expressioni

Tissue specificityi

Expressed weakly at G0/G1 and highly at late S and G2/M phase.

Inductioni

Increased by p53/TP53.1 Publication

Gene expression databases

BgeeiENSG00000002822.
CleanExiHS_MAD1L1.
ExpressionAtlasiQ9Y6D9. baseline and differential.
GenevisibleiQ9Y6D9. HS.

Organism-specific databases

HPAiCAB015338.
HPA003635.

Interactioni

Subunit structurei

Homodimer. Heterodimerizes with MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1 core complex. Perturbation of the original MAD1L1-MAD2L1 structure by the spindle checkpoint may decrease MAD2L1 affinity for MAD1L1. CDC20 can compete with MAD1L1 for MAD2L1 binding, until the attachment and/or tension dampen the checkpoint signal, preventing further release of MAD2L1 on to CDC20. Also able to interact with the BUB1/BUB3 complex and the viral Tax protein. Interacts with NEK2. Interacts with TPR; the interactions occurs in a microtubule-independent manner.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
A8KAD63EBI-742610,EBI-10174974
ALOX5P099175EBI-742610,EBI-79934
BAG5Q9UL156EBI-742610,EBI-356517
CCDC94Q9BW853EBI-742610,EBI-10300345
CCHCR1Q8TD31-35EBI-742610,EBI-10175300
HAUS1Q96CS23EBI-742610,EBI-2514791
LGALSLQ3ZCW25EBI-742610,EBI-10241423
MAD2L1Q1325714EBI-742610,EBI-78203
MFAP1P550815EBI-742610,EBI-1048159
NEBLO760415EBI-742610,EBI-2880203
PSMA1P257863EBI-742610,EBI-359352
RNF8O760645EBI-742610,EBI-373337
SPATA2Q9UM823EBI-742610,EBI-744066
TPM1P094933EBI-742610,EBI-351158
TPM3P067536EBI-742610,EBI-355607
TPM3Q5VU623EBI-742610,EBI-10184033
TPRP122702EBI-742610,EBI-1048528
TRIM29Q141346EBI-742610,EBI-702370
TSC22D3Q99576-33EBI-742610,EBI-10294415
TSHZ3A1L0U73EBI-742610,EBI-10171826
USP15Q9Y4E83EBI-742610,EBI-1043104
ZSCAN32I3L3J23EBI-742610,EBI-10178206

Protein-protein interaction databases

BioGridi113971. 66 interactors.
DIPiDIP-29654N.
IntActiQ9Y6D9. 65 interactors.
MINTiMINT-1435591.
STRINGi9606.ENSP00000265854.

Structurei

Secondary structure

1718
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi487 – 492Combined sources6
Helixi494 – 528Combined sources35
Turni537 – 539Combined sources3
Beta strandi540 – 547Combined sources8
Helixi549 – 575Combined sources27
Turni580 – 582Combined sources3
Helixi599 – 637Combined sources39
Beta strandi638 – 644Combined sources7
Turni645 – 647Combined sources3
Beta strandi648 – 653Combined sources6
Beta strandi663 – 667Combined sources5
Beta strandi675 – 678Combined sources4
Helixi683 – 685Combined sources3
Helixi687 – 693Combined sources7
Helixi700 – 715Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GO4X-ray2.05E/F/G/H485-584[»]
4DZOX-ray1.76A/B597-718[»]
ProteinModelPortaliQ9Y6D9.
SMRiQ9Y6D9.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y6D9.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni380 – 532Necessary for interaction with NEK21 PublicationAdd BLAST153

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili46 – 632Sequence analysisAdd BLAST587

Sequence similaritiesi

Belongs to the MAD1 family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG4593. Eukaryota.
ENOG410ZCEV. LUCA.
GeneTreeiENSGT00390000001316.
HOGENOMiHOG000004808.
HOVERGENiHBG052441.
InParanoidiQ9Y6D9.
KOiK06638.
OMAiVLHMSLN.
OrthoDBiEOG091G0IXP.
PhylomeDBiQ9Y6D9.
TreeFamiTF101083.

Family and domain databases

InterProiIPR008672. Mad1.
[Graphical view]
PANTHERiPTHR23168. PTHR23168. 1 hit.
PfamiPF05557. MAD. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9Y6D9-1) [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
MEDLGENTMV LSTLRSLNNF ISQRVEGGSG LDISTSAPGS LQMQYQQSMQ
60 70 80 90 100
LEERAEQIRS KSHLIQVERE KMQMELSHKR ARVELERAAS TSARNYEREV
110 120 130 140 150
DRNQELLTRI RQLQEREAGA EEKMQEQLER NRQCQQNLDA ASKRLREKED
160 170 180 190 200
SLAQAGETIN ALKGRISELQ WSVMDQEMRV KRLESEKQEL QEQLDLQHKK
210 220 230 240 250
CQEANQKIQE LQASQEARAD HEQQIKDLEQ KLSLQEQDAA IVKNMKSELV
260 270 280 290 300
RLPRLERELK QLREESAHLR EMRETNGLLQ EELEGLQRKL GRQEKMQETL
310 320 330 340 350
VGLELENERL LAKLQSWERL DQTMGLSIRT PEDLSRFVVE LQQRELALKD
360 370 380 390 400
KNSAVTSSAR GLEKARQQLQ EELRQVSGQL LEERKKRETH EALARRLQKR
410 420 430 440 450
VLLLTKERDG MRAILGSYDS ELTPAEYSPQ LTRRMREAED MVQKVHSHSA
460 470 480 490 500
EMEAQLSQAL EELGGQKQRA DMLEMELKML KSQSSSAEQS FLFSREEADT
510 520 530 540 550
LRLKVEELEG ERSRLEEEKR MLEAQLERRA LQGDYDQSRT KVLHMSLNPT
560 570 580 590 600
SVARQRLRED HSQLQAECER LRGLLRAMER GGTVPADLEA AAASLPSSKE
610 620 630 640 650
VAELKKQVES AELKNQRLKE VFQTKIQEFR KACYTLTGYQ IDITTENQYR
660 670 680 690 700
LTSLYAEHPG DCLIFKATSP SGSKMQLLET EFSHTVGELI EVHLRRQDSI
710
PAFLSSLTLE LFSRQTVA
Length:718
Mass (Da):83,067
Last modified:September 27, 2004 - v2
Checksum:iDA65529856A37EE3
GO
Isoform 2 (identifier: Q9Y6D9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: MEDLGENTMV...EQIRSKSHLI → MLPARGCVRK...PCIWPCPWHT
     66-157: Missing.

Note: No experimental confirmation available.
Show »
Length:626
Mass (Da):72,286
Checksum:iC0506A8710806387
GO

Sequence cautioni

The sequence AAC52059 differs from that shown. Reason: Frameshift at position 663.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti189 – 190EL → DV in AAC52059 (PubMed:9546394).Curated2
Sequence conflicti189 – 190EL → DV in AAD24498 (PubMed:10049595).Curated2
Sequence conflicti260K → E in AAC52059 (PubMed:9546394).Curated1
Sequence conflicti260K → E in AAD24498 (PubMed:10049595).Curated1
Sequence conflicti268Missing in AAC52059 (PubMed:9546394).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01970729S → L in a lymphoid cancer cell line; somatic mutation. 1 Publication1
Natural variantiVAR_01970859R → C in a prostate cancer cell line; somatic mutation. 1 PublicationCorresponds to variant rs28939694dbSNPEnsembl.1
Natural variantiVAR_019709160N → S.1 PublicationCorresponds to variant rs550573452dbSNPEnsembl.1
Natural variantiVAR_019710299T → A in lung cancer cell line; somatic mutation. 1 Publication1
Natural variantiVAR_019711360R → Q in a prostate cancer cell line; somatic mutation. 1 PublicationCorresponds to variant rs769418574dbSNPEnsembl.1
Natural variantiVAR_019712500T → M.2 PublicationsCorresponds to variant rs193231481dbSNPEnsembl.1
Natural variantiVAR_019713511E → K.1 PublicationCorresponds to variant rs377555260dbSNPEnsembl.1
Natural variantiVAR_019714516E → K in a breast cancer cell line; somatic mutation. 1 Publication1
Natural variantiVAR_019715556R → C in a prostate cancer cell line; somatic mutation. 1 PublicationCorresponds to variant rs371561369dbSNPEnsembl.1
Natural variantiVAR_019716556R → H in one individual with lung cancer. 1 PublicationCorresponds to variant rs755012008dbSNPEnsembl.1
Natural variantiVAR_019717558R → H in a cancer cell line. 3 PublicationsCorresponds to variant rs1801368dbSNPEnsembl.1
Natural variantiVAR_019718569E → K in a breast cancer cell line; somatic mutation. 1 PublicationCorresponds to variant rs201951163dbSNPEnsembl.1
Natural variantiVAR_019719572R → H in a cancer cell line. 1 PublicationCorresponds to variant rs1801500dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0561601 – 65MEDLG…KSHLI → MLPARGCVRKRTVWPRLARV LIVTLLTLELSYAPLPCQLS GVPYNTGDPVGRWARPCIWP CPWHT in isoform 2. 1 PublicationAdd BLAST65
Alternative sequenceiVSP_05616166 – 157Missing in isoform 2. 1 PublicationAdd BLAST92

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U33822 mRNA. Translation: AAC52059.1. Frameshift.
AF123318 mRNA. Translation: AAD20359.1.
AF083811 mRNA. Translation: AAD24498.1.
AK090959 mRNA. Translation: BAG52253.1.
AC005282 Genomic DNA. No translation available.
AC006433 Genomic DNA. No translation available.
AC069288 Genomic DNA. Translation: AAS07503.1.
AC104129 Genomic DNA. Translation: AAP21876.1.
AC110781 Genomic DNA. No translation available.
BC009964 mRNA. Translation: AAH09964.1.
CCDSiCCDS43539.1. [Q9Y6D9-1]
CCDS78201.1. [Q9Y6D9-3]
RefSeqiNP_001013858.1. NM_001013836.1. [Q9Y6D9-1]
NP_001013859.1. NM_001013837.1. [Q9Y6D9-1]
NP_001291452.1. NM_001304523.1. [Q9Y6D9-1]
NP_001291453.1. NM_001304524.1. [Q9Y6D9-3]
NP_003541.2. NM_003550.2. [Q9Y6D9-1]
UniGeneiHs.654838.

Genome annotation databases

EnsembliENST00000265854; ENSP00000265854; ENSG00000002822. [Q9Y6D9-1]
ENST00000399654; ENSP00000382562; ENSG00000002822. [Q9Y6D9-1]
ENST00000402746; ENSP00000384155; ENSG00000002822. [Q9Y6D9-3]
ENST00000406869; ENSP00000385334; ENSG00000002822. [Q9Y6D9-1]
GeneIDi8379.
KEGGihsa:8379.
UCSCiuc003slf.2. human. [Q9Y6D9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U33822 mRNA. Translation: AAC52059.1. Frameshift.
AF123318 mRNA. Translation: AAD20359.1.
AF083811 mRNA. Translation: AAD24498.1.
AK090959 mRNA. Translation: BAG52253.1.
AC005282 Genomic DNA. No translation available.
AC006433 Genomic DNA. No translation available.
AC069288 Genomic DNA. Translation: AAS07503.1.
AC104129 Genomic DNA. Translation: AAP21876.1.
AC110781 Genomic DNA. No translation available.
BC009964 mRNA. Translation: AAH09964.1.
CCDSiCCDS43539.1. [Q9Y6D9-1]
CCDS78201.1. [Q9Y6D9-3]
RefSeqiNP_001013858.1. NM_001013836.1. [Q9Y6D9-1]
NP_001013859.1. NM_001013837.1. [Q9Y6D9-1]
NP_001291452.1. NM_001304523.1. [Q9Y6D9-1]
NP_001291453.1. NM_001304524.1. [Q9Y6D9-3]
NP_003541.2. NM_003550.2. [Q9Y6D9-1]
UniGeneiHs.654838.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GO4X-ray2.05E/F/G/H485-584[»]
4DZOX-ray1.76A/B597-718[»]
ProteinModelPortaliQ9Y6D9.
SMRiQ9Y6D9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113971. 66 interactors.
DIPiDIP-29654N.
IntActiQ9Y6D9. 65 interactors.
MINTiMINT-1435591.
STRINGi9606.ENSP00000265854.

PTM databases

iPTMnetiQ9Y6D9.
PhosphoSitePlusiQ9Y6D9.

Polymorphism and mutation databases

BioMutaiMAD1L1.
DMDMi52783153.

Proteomic databases

EPDiQ9Y6D9.
PaxDbiQ9Y6D9.
PeptideAtlasiQ9Y6D9.
PRIDEiQ9Y6D9.

Protocols and materials databases

DNASUi8379.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265854; ENSP00000265854; ENSG00000002822. [Q9Y6D9-1]
ENST00000399654; ENSP00000382562; ENSG00000002822. [Q9Y6D9-1]
ENST00000402746; ENSP00000384155; ENSG00000002822. [Q9Y6D9-3]
ENST00000406869; ENSP00000385334; ENSG00000002822. [Q9Y6D9-1]
GeneIDi8379.
KEGGihsa:8379.
UCSCiuc003slf.2. human. [Q9Y6D9-1]

Organism-specific databases

CTDi8379.
DisGeNETi8379.
GeneCardsiMAD1L1.
HGNCiHGNC:6762. MAD1L1.
HPAiCAB015338.
HPA003635.
MalaCardsiMAD1L1.
MIMi602686. gene.
neXtProtiNX_Q9Y6D9.
OpenTargetsiENSG00000002822.
PharmGKBiPA372.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4593. Eukaryota.
ENOG410ZCEV. LUCA.
GeneTreeiENSGT00390000001316.
HOGENOMiHOG000004808.
HOVERGENiHBG052441.
InParanoidiQ9Y6D9.
KOiK06638.
OMAiVLHMSLN.
OrthoDBiEOG091G0IXP.
PhylomeDBiQ9Y6D9.
TreeFamiTF101083.

Enzyme and pathway databases

ReactomeiR-HSA-141444. Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
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.
SIGNORiQ9Y6D9.

Miscellaneous databases

ChiTaRSiMAD1L1. human.
EvolutionaryTraceiQ9Y6D9.
GeneWikiiMad1.
GenomeRNAii8379.
PROiQ9Y6D9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000002822.
CleanExiHS_MAD1L1.
ExpressionAtlasiQ9Y6D9. baseline and differential.
GenevisibleiQ9Y6D9. HS.

Family and domain databases

InterProiIPR008672. Mad1.
[Graphical view]
PANTHERiPTHR23168. PTHR23168. 1 hit.
PfamiPF05557. MAD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMD1L1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6D9
Secondary accession number(s): B3KR41
, Q13312, Q75MI0, Q86UM4, Q9UNH0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: September 27, 2004
Last modified: November 30, 2016
This is version 150 of the entry and version 2 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, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.