The mitotic checkpoint ensures that chromosomes are divided equally between daughter cells and is a primary mechanism preventing the chromosome instability often seen in aneuploid human tumors. This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. The encoded protein binds to centromeres during the prophase, metaphase, and early anaphase cell division stages and to kinetochore microtubules during metaphase. It is part of the MIS12 complex, which may be fundamental for kinetochore formation and proper chromosome segregation during mitosis. In mitotic human cells ZW10 resides in a complex with Rod and Zwilch, whereas another ZW10 partner, Zwint-1, is part of a separate complex of structural kinetochore components including Mis12 and Ndc80-Hec1. Zwint-1 is critical for recruiting ZW10 to unattached kinetochores. Depletion from human cells demonstrates that the ZW10 complex is essential for stable binding of a Mad1-Mad2 complex to unattached kinetochores. Thus, ZW10 functions as a linker between the core structural elements of the outer kinetochore and components that catalyze generation of the mitotic checkpoint-derived "stop anaphase" inhibitor.
Function:
Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum (By similarity).
Subunit:
Associated with a SNARE complex consisting of STX18, USE1L, BNIP1/SEC20L, and SEC22B through direct interaction with RINT1/TIP20L bound to BNIP1/SEC20L. Component of the RZZ complex composed of KNTC1/ROD, ZW10 and ZWILCH. Interacts with C19orf25, KNTC1 and ZWINT (By similarity).
Subcellular Location:
Cytoplasm (By similarity). Endoplasmic reticulum membrane; Peripheral membrane protein. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, spindle. Note=Dynamic pattern of localization during the cell cycle. In most cells at interphase, present diffusely in the cytoplasm. In prometaphase, associated with the kinetochore. At metaphase, detected both at the kinetochores and, most prominently, at the spindle, particularly at the spindle poles. In very early anaphase, detected on segregating kinetochores. In late anaphase and telophase, accumulates at the spindle midzone.
Similarity:
Belongs to the ZW10 family.
SWISS:
O43264
Gene ID:
26951
Database links:
Entrez Gene: 9183 Human
Entrez Gene: 26951 Mouse
Omim: 603954 Human
SwissProt: O43264 Human
SwissProt: O54692 Mouse
Unigene: 503886 Human
Unigene: 24791 Mouse
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