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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).

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.

Involvement in disease

Mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition

MVA7

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.

None

The disease may be caused by variants affecting the gene represented in this entry.

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

Post-translational modifications

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).

Sequence similarities

Belongs to the MAD1 family.

Tissue specificity

Isoform 1

Expressed in hepatocellular carcinomas and hepatoma cell lines (at protein level).

Isoform 3

Expressed in hepatocellular carcinomas and hepatoma cell lines (at protein level).

Cellular localization

  • Nucleus
  • Chromosome
  • Centromere
  • Kinetochore
  • Nucleus envelope
  • Cytoplasm
  • Cytoskeleton
  • Microtubule organizing center
  • Centrosome
  • Cytoplasm
  • Cytoskeleton
  • Spindle
  • Cytoplasm
  • Cytoskeleton
  • Spindle pole
  • 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).
  • Isoform 3
  • Cytoplasm

Alternative names

MAD1, TXBP181, MAD1L1, Mitotic spindle assembly checkpoint protein MAD1, Mitotic arrest deficient 1-like protein 1, Mitotic checkpoint MAD1 protein homolog, Tax-binding protein 181, MAD1-like protein 1, HsMAD1, hMAD1

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Molecular weight

83067Da

We found 6 products in 1 category

Primary Antibodies

Reactive species