细胞定位
Nucleus. Nucleus, nucleoplasm. Nucleus matrix. Chromosome. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle pole. Cytoplasm, cell cortex. Cell membrane; Lipid-anchor; Cytoplasmic side. Lateral cell membrane {ECO:0000250|UniProtKB:E9Q7G0}. Note=Mitotic cell cycle- dependent shuttling protein that relocalizes from the interphase nucleus to the spindle poles and cell cortex (PubMed:1541636, PubMed:10811826). The localization to the spindle poles is regulated by AAAS (PubMed:26246606). In interphase, resides in the nuclear matrix (PubMed:1541630, PubMed:1541636, PubMed:23921553). In prophase, restricted to the interchromatin or condensed chromosome space (PubMed:10811826). In prometaphase, after nuclear envelope disassembly, forms aggregates both in the spindle midzone and at duplicated centrosomes and astral microtubules (MTs) of the bipolar spindle apparatus (PubMed:10811826). Translocates from the spindle midzone towards the spindle poles along spindle fibers in a MT- and dynein- dynactin-dependent manner until the anaphase onset (PubMed:1541636, PubMed:10811826). In metaphase, recruited to the polar cortical region in a GPSM2- and GNAI1-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901). Excluded from the metaphase equatorial cortical region in a RanGTP-dependent manner (PubMed:22327364, PubMed:23870127). Phosphorylation on Thr-2055 by CDK1 results in its localization at spindle poles in metaphase, but not at the cell cortex (PubMed:23921553). In anaphase, recruited and anchored at the cell membrane of the polar cortical region in a EPB41-, EPB41L2-, phosphatidylinositol-dependent and GPSM2- and G(i) alpha proteins-independent manner (PubMed:23870127, PubMed:24996901, PubMed:24109598, PubMed:24371089). Excluded from the anaphase equatorial region of the cell cortex in a RACGAP1- and KIF23-dependent and RanGTP-independent manner (PubMed:24996901). Associated with astral MTs emanating from the spindle poles during anaphase (PubMed:12445386, PubMed:24996901). Nonphosphorylated Thr-2055 localizes at the cell cortex, weakly during metaphase and more prominently during anaphase in a phosphatase PPP2CA-dependent manner (PubMed:23921553). As mitosis progresses it reassociates with telophase chromosomes very early during nuclear reformation, before substantial accumulation of lamins on chromosomal surfaces is evident (PubMed:1541636). Localizes to the tips of cortical MTs in prometaphase (PubMed:26765568). Localizes along MTs and specifically to both MT plus and minus ends (PubMed:26765568) Accumulates also at MT tips near the cell periphery (PubMed:26765568) Colocalizes with GPSM2 at mitotic spindle poles during mitosis (PubMed:11781568, PubMed:21816348). Colocalizes with SPAG5 at mitotic spindle at prometaphase and at mitotic spindle poles at metaphase and anaphase (PubMed:27462074). Colocalizes with ABRO1 at mitotic spindle poles (PubMed:26195665). Colocalized with TNKS from prophase through to anaphase in mitosis (PubMed:16076287). Colocalizes with tubulin alpha (PubMed:12445386). CCSAP is essential for its centrosomal localization (PubMed:26562023). In horizontally retinal progenitor dividing cells, localized to the lateral cortical region (By similarity) {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:10811826, ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:1541630, ECO:0000269|PubMed:1541636, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26246606, ECO:0000269|PubMed:26562023, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074} [Isoform 4]: Cytoplasm, cytosol. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle pole. Note=During interphase, mainly clustered at the centrosomal region in the cytosol After entry into mitosis, detected at mitotic spindle poles
功能
Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:
7769006, PubMed:
17172455, PubMed:
19255246, PubMed:
24996901, PubMed:
26195665, PubMed:
27462074). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:
12445386, PubMed:
11956313). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:
23870127, PubMed:
24109598, PubMed:
24996901, PubMed:
26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:
23027904, PubMed:
22327364, PubMed:
23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:
22327364, PubMed:
23921553, PubMed:
24996901, PubMed:
24371089). Binds also to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:
24996901, PubMed:
24371089). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:
21816348). Plays a role in mitotic MT aster assembly (PubMed:
11163243, PubMed:
11229403, PubMed:
12445386). Involved in anastral spindle assembly (PubMed:
25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:
16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:
10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity).