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NUMA1

This gene encodes a large protein that forms a structural component of the nuclear matrix. The encoded protein interacts with microtubules and plays a role in the formation and organization of the mitotic spindle during cell division. Chromosomal translocation of this gene with the RARA (retinoic acid receptor, alpha) gene on chromosome 17 have been detected in patients with acute promyelocytic leukemia. Alternative splicing results in multiple transcript variants.
Protein class

Cancer-related genes, Plasma proteins

Predicted location

Intracellular

Single cell type specificity

Low cell type specificity

Immune cell specificity

Low immune cell specificity

Cell line specificity

Low cell line specificity

Interaction

Homodimer (PubMed:10075938). Also forms multiarm oligomers by association of C-terminal tail domains, oligomers may further assemble to form a hexagonal nuclear lattice-like network (PubMed:10075938). Associates with the dynein-dynactin complex; this association promotes the transport and accumulation of NUMA1 at the mitotic spindle poles that is inhibited by the BRISC complex in a PLK1-dependent manner (PubMed:10811826, PubMed:17172455, PubMed:23027904, PubMed:22327364, PubMed:26195665). Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (PubMed:26766442). Interacts (via C-terminus) with microtubules (MTs); this interaction is direct and promotes both MT bundle formation and stability in a dynein-dynactin complex- and CDK1-independent manner (PubMed:12445386, PubMed:11956313, PubMed:26765568). Interacts with EPB41 and EPB41L2; these interactions are negatively regulated by CDK1 during metaphase and are important for anaphase-specific localization of NUMA1 in symmetrically dividing cells (PubMed:23870127, PubMed:24996901). Interacts (via C-terminus) with GPSM2 (via TPR repeats); this interaction is direct, prevented by competitive binding of INSC, is inhibited in a PLK1-dependent manner, blocks the association of NUMA1 with MTs and inhibits NUMA1-induced MT bundle formation, prevents the association of NUMA1 with SPAG5, induces mitotic spindle pole localization of GPSM2, both metaphase cell cortex localization of NUMA1 and mitotic spindle organization (PubMed:11781568, PubMed:12445386, PubMed:22327364, PubMed:24109598, PubMed:27462074, PubMed:21816348). Does not interact with GPSM2 during anaphase (PubMed:23870127). Interacts (via C-terminus) with the nuclear importin alpha/importin beta receptor; this interaction is inhibited by RanGTP (PubMed:11163243). Interacts (via C-terminus) with KPNB1; this interaction is inhibited by RanGTP and the BRISC complex (PubMed:11229403, PubMed:26195665). Interacts with ABRAXAS2 and the BRISC complex; these interactions regulate mitotic spindle assembly (PubMed:26195665). Interacts (via N-terminal end of the coiled-coil domain) with RAE1; this interaction promotes mitotic spindle formation (PubMed:17172455). Interacts (via C-terminus) with SPAG5 (via C-terminus); this interaction promotes the recruitment of SPAG5 to the MTs at spindle poles in a dynein-dynactin-dependent manner and regulates mitotic spindle organization and proper chromosome alignment during mitosis (PubMed:27462074). Interacts with TNKS; this interaction occurs at the onset of mitosis (PubMed:12080061, PubMed:16076287). Interacts with TNKS2 (PubMed:12080061). Interacts with tubulin (PubMed:11956313). Interacts with KHDC3L (via C-terminus) (By similarity).

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