NUMA1
entrez
4926
canonical
uniprot
Q14980
canonical
ensembl
ENSG00000137497
resolver
ensp
ENSP00000351851
resolver
ensp
ENSP00000377298
resolver
ensp
ENSP00000478624
resolver
ensp
ENSP00000533504
resolver
ensp
ENSP00000533507
resolver
ensp
ENSP00000533508
resolver
ensp
ENSP00000533511
resolver
ensp
ENSP00000591334
resolver
ensp
ENSP00000637580
resolver
ensp
ENSP00000637582
resolver
ensp
ENSP00000637588
resolver
genesymbol
NUMA1
resolver
genesymbol_syn
NMP22
resolver
genesymbol_syn
NUMA
resolver
hgnc
HGNC:8059
resolver
uniprot
H0YH75
resolver
uniprot
Q14981
resolver
uniprot
Q3SYK8
resolver
uniprot
Q9BTE9
resolver
uniprot_entry
NUMA1_HUMAN
resolver
uniprot_entry
Q3SYK8_HUMAN
resolver
uniprot_sec
H0YH75
resolver
uniprot_sec
Q14981
resolver
uniprot_sec
Q9BTE9
resolver
amino_acid_sequence
MTLHATRGAALLSWVNSLHVADPVEAVLQLQDCSIFIKIIDRIHGTEEGQQILKQPVSERLDFVCSFLQKNRKHPSSPECLVSAQKVLEGSELELAKMTMLLLYHSTMSSKSPRDWEQFEYKIQAELAVILKFVLDHEDGLNLNEDLENFLQKAPVPSTCSSTFPEELSPPSHQAKREIRFLELQKVASSSSGNNFLSGSPASPMGDILQTPQFQMRRLKKQLADERSNRDELELELAENRKLLTEKDAQIAMMQQRIDRLALLNEKQAASPLEPKELEELRDKNESLTMRLHETLKQCQDLKTEKSQMDRKINQLSEENGDLSFKLREFASHLQQLQDALNELTEEHSKATQEWLEKQAQLEKELSAALQDKKCLEEKNEILQGKLSQLEEHLSQLQDNPPQEKGEVLGDVLQLETLKQEAATLAANNTQLQARVEMLETERGQQEAKLLAERGHFEEEKQQLSSLITDLQSSISNLSQAKEELEQASQAHGARLTAQVASLTSELTTLNATIQQQDQELAGLKQQAKEKQAQLAQTLQQQEQASQGLRHQVEQLSSSLKQKEQQLKEVAEKQEATRQDHAQQLATAAEEREASLRERDAALKQLEALEKEKAAKLEILQQQLQVANEARDSAQTSVTQAQREKAELSRKVEELQACVETARQEQHEAQAQVAELELQLRSEQQKATEKERVAQEKDQLQEQLQALKESLKVTKGSLEEEKRRAADALEEQQRCISELKAETRSLVEQHKRERKELEEERAGRKGLEARLQQLGEAHQAETEVLRRELAEAMAAQHTAESECEQLVKEVAAWRERYEDSQQEEAQYGAMFQEQLMTLKEECEKARQELQEAKEKVAGIESHSELQISRQQNELAELHANLARALQQVQEKEVRAQKLADDLSTLQEKMAATSKEVARLETLVRKAGEQQETASRELVKEPARAGDRQPEWLEEQQGRQFCSTQAALQAMEREAEQMGNELERLRAALMESQGQQQEERGQQEREVARLTQERGRAQADLALEKAARAELEMRLQNALNEQRVEFATLQEALAHALTEKEGKDQELAKLRGLEAAQIKELEELRQTVKQLKEQLAKKEKEHASGSGAQSEAAGRTEPTGPKLEALRAEVSKLEQQCQKQQEQADSLERSLEAERASRAERDSALETLQGQLEEKAQELGHSQSALASAQRELAAFRTKVQDHSKAEDEWKAQVARGRQEAERKNSLISSLEEEVSILNRQVLEKEGESKELKRLVMAESEKSQKLEERLRLLQAETASNSARAAERSSALREEVQSLREEAEKQRVASENLRQELTSQAERAEELGQELKAWQEKFFQKEQALSTLQLEHTSTQALVSELLPAKHLCQQLQAEQAAAEKRHREELEQSKQAAGGLRAELLRAQRELGELIPLRQKVAEQERTAQQLRAEKASYAEQLSMLKKAHGLLAEENRGLGERANLGRQFLEVELDQAREKYVQELAAVRADAETRLAEVQREAQSTARELEVMTAKYEGAKVKVLEERQRFQEERQKLTAQVEQLEVFQREQTKQVEELSKKLADSDQASKVQQQKLKAVQAQGGESQQEAQRLQAQLNELQAQLSQKEQAAEHYKLQMEKAKTHYDAKKQQNQELQEQLRSLEQLQKENKELRAEAERLGHELQQAGLKTKEAEQTCRHLTAQVRSLEAQVAHADQQLRDLGKFQVATDALKSREPQAKPQLDLSIDSLDLSCEEGTPLSITSKLPRTQPDGTSVPGEPASPISQRLPPKVESLESLYFTPIPARSQAPLESSLDSLGDVFLDSGRKTRSARRRTTQIINITMTKKLDVEEPDSANSSFYSTRSAPASQASLRATSSTQSLARLGSPDYGNSALLSLPGYRPTTRSSARRSQAGVSSGAPPGRNSFYMGTCQDEPEQLDDWNRIAELQQRNRVCPPHLKTCYPLESRPSLSLGTITDEEMKTGDPQETLRRASMQPIQIAEGTGITTRQQRKRVSLEPHQGPGTPESKKATSCFPRPMTPRDRHEGRKQSTTEAQKKAAPASTKQADRRQSMAFSILNTPKKLGNSLLRRGASKKALSKASPNTRSGTRRSPRIATTTASAATAAAIGATPRAKGKAKH
uniprot
proteins
function
FUNCTION: 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:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). 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:11956313, PubMed:12445386). 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:22327364, PubMed:23027904, 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:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). 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). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}.
uniprot
proteins
mass_dalton
238260
uniprot
proteins
mutagenesis
MUTAGEN 1910; /note="E->A: Abolishes interaction with GPSM2."; /evidence="ECO:0000269|PubMed:21816348"; MUTAGEN 1984; /note="R->G: No effect on nuclear localization."; /evidence="ECO:0000269|PubMed:7962183"; MUTAGEN 1988; /note="K->E: Abolishes nuclear localization."; /evidence="ECO:0000269|PubMed:7962183"; MUTAGEN 2015; /note="T->A: Abolishes association with the mitotic spindle. Increases premature accumulation at the cell cortex during metaphase; when associated with A-2055 and A-2087."; /evidence="ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:7769006"; MUTAGEN 2055; /note="T->A: Increases premature accumulation at the cell membrane of the polar cortical region in prophase and metaphase. Reduces association with the mitotic spindle. Increased randomization of spindle orientation. Increases premature accumulation at the cell cortex during metaphase; when associated with A-2015 and A-2087."; /evidence="ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:7769006"; MUTAGEN 2055; /note="T->D: Increases localization at the spindle poles. Decreases localization at the cell cortex."; /evidence="ECO:0000269|PubMed:24109598"; MUTAGEN 2055; /note="T->E: Absence of cell membrane association even in anaphase. Increased localization at spindle poles and chromosome congression defects. Does not localize to the cortex in either metaphase or anaphase. Increased randomization of spindle orientation."; /evidence="ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24371089"; MUTAGEN 2087; /note="S->A: Abolishes association with the mitotic spindle. Increases premature accumulation at the cell cortex during metaphase; when associated with A-2015 and A-2055."; /evidence="ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:7769006"; MUTAGEN 2106; /note="T->A: Abolishes association with the mitotic spindle."; /evidence="ECO:0000269|PubMed:7769006
uniprot
proteins
post_translational_modification
PTM: Phosphorylation and dephosphorylation on Thr-2055 regulates the extent of cortical NUMA1 and the dynein-dynactin complex localization during mitotic metaphase and anaphase (PubMed:23921553). In metaphase, phosphorylation on Thr-2055 occurs in a kinase CDK1-dependent manner; this phosphorylation maintains low levels of cortical dynein-dynactin complex at metaphase, and hence proper spindle positioning (PubMed:23921553, PubMed:24371089, PubMed:7769006). In anaphase, dephosphorylated on Thr-2055 by phosphatase PPP2CA; this dephosphorylation stimulates its membrane association and with the dynein-dynactin complex its enrichment at the cell cortex, and hence robust spindle elongation (PubMed:23921553, PubMed:24371089). Probably also phosphorylated on Thr-2015 and Ser-2087 by CDK1; these phosphorylations may regulate its cell cortex recruitment during metaphase and anaphase (PubMed:23870127). Phosphorylated on Thr-1047, Ser-1769, Ser-1772, Ser-1789 and Ser-1834 by PLK1; these phosphorylations induce cortical dynein-dynactin complex dissociation from the NUMA1-GPSM2 complex and negatively regulates cortical dynein-dynactin complex localization (PubMed:22327364). {ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:7769006}.; PTM: ADP-ribosylated by TNKS at the onset of mitosis; ADP-ribosylation is not required for its localization to spindle poles (PubMed:16076287). {ECO:0000269|PubMed:16076287}.; PTM: O-glycosylated during cytokinesis at sites identical or close to phosphorylation sites, this interferes with the phosphorylation status (PubMed:20068230). {ECO:0000269|PubMed:20068230}.; PTM: Ubiquitinated with 'Lys-63'-linked polyubiquitin chains. Deubiquitination by the BRISC complex is important for the incorporation of NUMA1 into mitotic spindle poles and normal spindle pole function, probably by modulating interactions between NUMA1, dynein-dynactin complex and importin-beta. {ECO:0000269|PubMed:26195665}.
uniprot
proteins
pubmed
10075938
uniprot
proteins
pubmed
10811826
uniprot
proteins
pubmed
11163243
uniprot
proteins
pubmed
11229403
uniprot
proteins
pubmed
11781568
uniprot
proteins
pubmed
11956313
uniprot
proteins
pubmed
12080061
uniprot
proteins
pubmed
12445386
uniprot
proteins
pubmed
1541630
uniprot
proteins
pubmed
1541636
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
16076287
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17172455
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17924679
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19255246
uniprot
proteins
pubmed
19367720
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068230
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20137953
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21816348
uniprot
proteins
pubmed
22327364
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23027904
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23870127
uniprot
proteins
pubmed
23921553
uniprot
proteins
pubmed
24109598
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24371089
uniprot
proteins
pubmed
24996901
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25657325
uniprot
proteins
pubmed
25772364
uniprot
proteins
pubmed
26195665
uniprot
proteins
pubmed
26246606
uniprot
proteins
pubmed
26562023
uniprot
proteins
pubmed
26765568
uniprot
proteins
pubmed
26766442
uniprot
proteins
pubmed
27462074
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
7769006
uniprot
proteins
pubmed
7962183
uniprot
proteins
pubmed
8408288
uniprot
proteins
pubmed
8505359
uniprot
proteins
pubmed
9730450
uniprot
proteins
sequence_length
2115
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:1541630, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:27462074}. Nucleus, nucleoplasm {ECO:0000269|PubMed:10811826}. Nucleus matrix {ECO:0000269|PubMed:10075938, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:1541636, ECO:0000269|PubMed:7962183}. Chromosome {ECO:0000269|PubMed:1541630}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:26765568}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:10811826, ECO:0000269|PubMed:1541630, ECO:0000269|PubMed:1541636, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26562023, ECO:0000269|PubMed:26765568}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:10811826, ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:11956313, 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:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26246606, ECO:0000269|PubMed:26562023, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000269|PubMed:7962183}. Cytoplasm, cell cortex {ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24996901}. Cell membrane {ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901}; Lipid-anchor {ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901}; Cytoplasmic side {ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901}. 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:10811826, PubMed:1541636). 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:10811826, PubMed:1541636). 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:24109598, PubMed:24371089, PubMed:24996901). 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). Also accumulates 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}.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm, cytosol {ECO:0000269|PubMed:7962183}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:7962183}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:7962183}. Note=During interphase, mainly clustered at the centrosomal region in the cytosol. After entry into mitosis, detected at mitotic spindle poles. {ECO:0000269|PubMed:7962183}.; SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm, cytosol {ECO:0000269|PubMed:7962183}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:7962183}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:7962183}. Note=During interphase, mainly clustered at the centrosomal region in the cytosol. After entry into mitosis, detected at mitotic spindle poles. {ECO:0000269|PubMed:7962183}.
uniprot
proteins