MAD1L1
entrez
8379
canonical
uniprot
Q9Y6D9
canonical
ensembl
ENSG00000002822
resolver
ensp
ENSP00000265854
resolver
ensp
ENSP00000382562
resolver
ensp
ENSP00000384155
resolver
ensp
ENSP00000385334
resolver
ensp
ENSP00000725986
resolver
genesymbol
MAD1L1
resolver
genesymbol_syn
MAD1
resolver
genesymbol_syn
TXBP181
resolver
hgnc
HGNC:6762
resolver
uniprot
B3KR41
resolver
uniprot
Q13312
resolver
uniprot
Q75MI0
resolver
uniprot
Q86UM4
resolver
uniprot
Q9UNH0
resolver
uniprot_entry
MD1L1_HUMAN
resolver
uniprot_sec
B3KR41
resolver
uniprot_sec
Q13312
resolver
uniprot_sec
Q75MI0
resolver
uniprot_sec
Q86UM4
resolver
uniprot_sec
Q9UNH0
resolver
amino_acid_sequence
MEDLGENTMVLSTLRSLNNFISQRVEGGSGLDISTSAPGSLQMQYQQSMQLEERAEQIRSKSHLIQVEREKMQMELSHKRARVELERAASTSARNYEREVDRNQELLTRIRQLQEREAGAEEKMQEQLERNRQCQQNLDAASKRLREKEDSLAQAGETINALKGRISELQWSVMDQEMRVKRLESEKQELQEQLDLQHKKCQEANQKIQELQASQEARADHEQQIKDLEQKLSLQEQDAAIVKNMKSELVRLPRLERELKQLREESAHLREMRETNGLLQEELEGLQRKLGRQEKMQETLVGLELENERLLAKLQSWERLDQTMGLSIRTPEDLSRFVVELQQRELALKDKNSAVTSSARGLEKARQQLQEELRQVSGQLLEERKKRETHEALARRLQKRVLLLTKERDGMRAILGSYDSELTPAEYSPQLTRRMREAEDMVQKVHSHSAEMEAQLSQALEELGGQKQRADMLEMELKMLKSQSSSAEQSFLFSREEADTLRLKVEELEGERSRLEEEKRMLEAQLERRALQGDYDQSRTKVLHMSLNPTSVARQRLREDHSQLQAECERLRGLLRAMERGGTVPADLEAAAASLPSSKEVAELKKQVESAELKNQRLKEVFQTKIQEFRKACYTLTGYQIDITTENQYRLTSLYAEHPGDCLIFKATSPSGSKMQLLETEFSHTVGELIEVHLRRQDSIPAFLSSLTLELFSRQTVA
uniprot
proteins
disease_involvement
DISEASE: Mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition (MVA7) [MIM:620189]: A form of mosaic variegated aneuploidy syndrome, a severe disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. MVA7 is an autosomal recessive form characterized by increased susceptibility to benign and malignant neoplasms beginning in early childhood. Affected individuals show dysmorphic facies and may have early developmental delay. {ECO:0000269|PubMed:36322655}. Note=The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Note=Defects in MAD1L1 are involved in the development and/or progression of various types of cancer. {ECO:0000269|PubMed:10597320, ECO:0000269|PubMed:11423979}.
uniprot
proteins
function
FUNCTION: Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:10049595, PubMed:20133940, PubMed:29162720). Forms a heterotetrameric complex with the closed conformation form of MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, recruits an open conformation of MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint signaling (PubMed:29162720). {ECO:0000269|PubMed:10049595, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:36322655}.; FUNCTION: [Isoform 3]: Sequesters MAD2L1 in the cytoplasm preventing its function as an activator of the mitotic spindle assembly checkpoint (SAC) resulting in SAC impairment and chromosomal instability in hepatocellular carcinomas. {ECO:0000269|PubMed:19010891}.
uniprot
proteins
mass_dalton
83067
uniprot
proteins
mutagenesis
MUTAGEN 1..485; /note="Missing: Defective dimerization. Abolishes binding to the closed and open conformations of MAD2L1. Impairs mitotic checkpoint signaling abolishing mitotic arrest, and shortens the duration of mitosis."; /evidence="ECO:0000269|PubMed:29162720"; MUTAGEN 79..82; /note="KRAR->LLAL: Loss of nuclear localization."; /evidence="ECO:0000269|PubMed:19010891"; MUTAGEN 540..551; /note="Missing: Loss of interaction with MAD2L1."; /evidence="ECO:0000269|PubMed:19010891"; MUTAGEN 541; /note="K->A: Abolishes binding to closed and open conformations of MAD2L1 and impairs mitotic checkpint signaling abolishing mitotic arrest, and shortens the duration of mitosis; in association with A-543."; /evidence="ECO:0000269|PubMed:29162720"; MUTAGEN 543; /note="L->A: Abolishes binding to closed and open conformations of MAD2L1 and impairs mitotic checkpoint signaling abolishing mitotic arrest, and shortens the duration of mitosis; in association with A-541."; /evidence="ECO:0000269|PubMed:29162720"; MUTAGEN 597..718; /note="Missing: Defective dimerization. Reduces binding to the closed and open conformations of MAD2L1. Impairs mitotic checkpoint signaling abolishing mitotic arrest, and shortens the duration of mitosis."; /evidence="ECO:0000269|PubMed:29162720"; MUTAGEN 598; /note="S->A,E: Does not impact the duration of mitosis."; /evidence="ECO:0000269|PubMed:29162720"; MUTAGEN 610; /note="S->A,E: Impairs mitotic checkpoint signaling and shortens the duration of mitosis."; /evidence="ECO:0000269|PubMed:29162720"; MUTAGEN 634; /note="Y->E: Reduces binding to closed and open conformations of MAD2L1. Impairs mitotic checkpoint signaling abolishing mitotic arrest, and shortens the duration of mitosis."; /evidence="ECO:0000269|PubMed:29162720"; MUTAGEN 634; /note="Y->F: Reduces binding to closed and open conformations of MAD2L1. Does not impact the duration of mitosis."; /evidence="ECO:0000269|PubMed:29162720"; MUTAGEN 716; /note="T->A,E: Reduces binding to closed and open conformations of MAD2L1. Impairs mitotic checkpoint signaling and shortens the duration of mitosis."; /evidence="ECO:0000269|PubMed:29162720
uniprot
proteins
post_translational_modification
PTM: Phosphorylated; by BUB1 (PubMed:10198256). Become hyperphosphorylated in late S through M phases or after mitotic spindle damage (PubMed:9546394). Phosphorylated; by TTK (PubMed:29162720). {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:9546394}.
uniprot
proteins
protein_family
MAD1 family
uniprot
proteins
pubmed
10049595
uniprot
proteins
pubmed
10198256
uniprot
proteins
pubmed
10366450
uniprot
proteins
pubmed
10597320
uniprot
proteins
pubmed
11423979
uniprot
proteins
pubmed
12006501
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14978040
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18981471
uniprot
proteins
pubmed
19010891
uniprot
proteins
pubmed
19273613
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20133940
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22351768
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24374861
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
29162720
uniprot
proteins
pubmed
36322655
uniprot
proteins
pubmed
9546394
uniprot
proteins
sequence_length
718
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19010891, ECO:0000269|PubMed:9546394}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:22351768, ECO:0000269|PubMed:29162720}. Nucleus envelope {ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:22351768}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:9546394}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:9546394}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:22351768}. Note=Co-localizes with TPR at the nucleus envelope during interphase and throughout the cell cycle (PubMed:18981471, PubMed:22351768). From the beginning to the end of mitosis, it is seen to move from a diffusely nuclear distribution to the centrosome, to the spindle midzone and finally to the midbody (PubMed:9546394). Localizes to kinetochores during prometaphase (PubMed:22351768, PubMed:29162720). Does not localize to kinetochores during metaphase (PubMed:29162720). Colocalizes with NEK2 at the kinetochore (PubMed:14978040). Colocalizes with IK at spindle poles during metaphase and anaphase (PubMed:22351768). {ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:22351768, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:9546394}.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm {ECO:0000269|PubMed:19010891}.
uniprot
proteins