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Details on Person UniProt:Q9Y6D9 MAD1L1

Class:Id	ReferenceGeneProduct:141442
_chainChangeLog	chain:1-718 added on Fri February 6 2015
_displayName	UniProt:Q9Y6D9 MAD1L1
_timestamp	2026-02-20 21:31:50
chain	chain:1-718
checksum	DA65529856A37EE3
comment	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).FUNCTION 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.SUBUNIT Homodimer (PubMed:29162720, PubMed:9546394). Dimerizes via its N- and C- terminal regions (PubMed:29162720). Heterodimerizes with MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1 core complex (PubMed:12006501, PubMed:18981471, PubMed:22351768, PubMed:9546394). Interacts with the closed conformation form of MAD2L1 (C-MAD2) and open conformation form of MAD2L1 (O-MAD2) (PubMed:29162720). It is unclear whether MAD1L1 dimerization promotes the conversion of closed to open conformation of MAD2L1 (PubMed:29162720). 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 (PubMed:12006501). Perturbation of the original MAD1L1-MAD2L1 structure by the spindle checkpoint may decrease MAD2L1 affinity for MAD1L1 (PubMed:12006501). 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 (PubMed:12006501). Also able to interact with the BUB1/BUB3 complex (PubMed:10198256). Interacts with NEK2 (PubMed:14978040). Interacts with TTK (PubMed:29162720). Interacts with TPR; the interactions occurs in a microtubule-independent manner (PubMed:18981471, PubMed:19273613, PubMed:20133940). Interacts with IK (PubMed:22351768). Interacts with the viral Tax protein (PubMed:9546394). Interacts with PRAP1 (PubMed:24374861).SUBUNIT Interacts with MAD2L1; this interaction leads to the cytoplasmic sequestration of MAD2L1 (PubMed:19010891). Interacts with PRAP1 (PubMed:24374861).SUBCELLULAR LOCATION 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).SUBCELLULAR LOCATION Expressed in hepatocellular carcinomas and hepatoma cell lines (at protein level).TISSUE SPECIFICITY Expressed in hepatocellular carcinomas and hepatoma cell lines (at protein level).INDUCTION Increased by p53/TP53.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).DISEASE The disease may be caused by variants affecting the gene represented in this entry.DISEASE Defects in MAD1L1 are involved in the development and/or progression of various types of cancer.SIMILARITY Belongs to the MAD1 family.
created	[InstanceEdit:141435] Matthews, L, 2004-09-19 23:16:45
description	recommendedName: Mitotic spindle assembly checkpoint protein MAD1 alternativeName: Mitotic arrest deficient 1-like protein 1 shortName: MAD1-like protein 1 alternativeName: Mitotic checkpoint MAD1 protein homolog shortName: HsMAD1 shortName: hMAD1 alternativeName: Tax-binding protein 181
geneName	MAD1L1 MAD1 TXBP181
identifier	Q9Y6D9
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Cell cycle Cell division Centromere Chromosome Coiled coil Cytoplasm Cytoskeleton Disease variant Isopeptide bond Kinetochore Mitosis Nucleus Phosphoprotein Proteomics identification Reference proteome Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	MAD1L1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8990829] ENSEMBL:ENSG00000002822 MAD1L1 [Homo sapiens]
secondaryIdentifier	MD1L1_HUMAN B3KR41 Q13312 Q75MI0 Q86UM4 Q9UNH0
sequenceLength	718
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8967471] UniProt:Q9Y6D9-1 MAD1L1 [Homo sapiens] [ReferenceIsoform:8967472] UniProt:Q9Y6D9-3 MAD1L1 [Homo sapiens] [ReferenceIsoform:9750354] UniProt:Q9Y6D9-4 MAD1L1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:141433] MAD1L1 [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q9Y6D9 MAD1L1 (141442)