MAD1L1

MAD1L1 is a component of the mitotic spindle-assembly checkpoint that prevents the onset of anaphase until all chromosome are properly aligned at the metaphase plate. MAD1L1 functions as a homodimer and interacts with MAD2L1. MAD1L1 may play a role in cell cycle control and tumor suppression.

Full Name

Mitotic Arrest Deficient 1 Like 1

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.

Biological Process

Attachment of mitotic spindle microtubules to kinetochoreManual Assertion Based On ExperimentIBA:GO_Central
Cell divisionIEA:UniProtKB-KW
Cytoplasmic sequestering of proteinIDA:UniProtKB
Deactivation of mitotic spindle assembly checkpointIDA:UniProtKB
Mitotic spindle assembly checkpoint signalingManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of T cell proliferationIEA:Ensembl
Positive regulation of mitotic cell cycle spindle assembly checkpointManual Assertion Based On ExperimentIDA:ComplexPortal
Regulation of metaphase plate congressionManual Assertion Based On ExperimentIDA:UniProtKB
Thymus developmentIEA:Ensembl

Cellular Location

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:22351768, PubMed:18981471).
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).

Involvement in disease

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

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).