E9Q7G0 · NUMA1_MOUSE

  • Protein
    Nuclear mitotic apparatus protein 1
  • Gene
    Numa1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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:19255246, PubMed:24109598, PubMed:26765568).
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:26765568).
Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (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:24109598, PubMed:26765568).
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. Binds also to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (By similarity).
Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:26765568).
Plays a role in mitotic MT aster assembly. Involved in anastral spindle assembly. Positively regulates TNKS protein localization to spindle poles in mitosis. Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (By similarity).
Required for epidermal differentiation and hair follicle morphogenesis (PubMed:26765568).

GO annotations

AspectTerm
Cellular Componentcell cortex region
Cellular Componentcentrosome
Cellular Componentchromosome
Cellular Componentcortical microtubule
Cellular Componentcytoplasmic microtubule bundle
Cellular Componentcytosol
Cellular Componentdendrite
Cellular Componentlateral cell cortex
Cellular Componentlateral plasma membrane
Cellular Componentmicrotubule bundle
Cellular Componentmicrotubule minus-end
Cellular Componentmicrotubule plus-end
Cellular Componentmitotic spindle astral microtubule
Cellular Componentmitotic spindle midzone
Cellular Componentmitotic spindle pole
Cellular Componentneuronal cell body
Cellular Componentnuclear matrix
Cellular Componentnucleoplasm
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentprotein-containing complex
Cellular Componentspindle microtubule
Cellular Componentspindle pole
Cellular Componentspindle pole centrosome
Molecular Functiondisordered domain specific binding
Molecular Functiondynein complex binding
Molecular Functionmicrotubule binding
Molecular Functionmicrotubule minus-end binding
Molecular Functionmicrotubule plus-end binding
Molecular Functionphosphatidylinositol binding
Molecular Functiontubulin binding
Biological Processanastral spindle assembly
Biological Processastral microtubule organization
Biological Processcell division
Biological Processestablishment of mitotic spindle orientation
Biological Processmeiotic cell cycle
Biological Processmicrotubule bundle formation
Biological Processpositive regulation of BMP signaling pathway
Biological Processpositive regulation of chromosome segregation
Biological Processpositive regulation of chromosome separation
Biological Processpositive regulation of hair follicle development
Biological Processpositive regulation of intracellular transport
Biological Processpositive regulation of keratinocyte differentiation
Biological Processpositive regulation of microtubule polymerization
Biological Processpositive regulation of mitotic spindle elongation
Biological Processpositive regulation of protein localization to cell cortex
Biological Processpositive regulation of protein localization to spindle pole body
Biological Processpositive regulation of spindle assembly
Biological Processregulation of metaphase plate congression
Biological Processregulation of mitotic spindle organization

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Nuclear mitotic apparatus protein 1
  • Alternative names
    • Nuclear mitotic apparatus protein
      (NuMA protein
      )

Gene names

    • Name
      Numa1

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    E9Q7G0
  • Secondary accessions
    • Q80Y35

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Nucleus, nucleoplasm
Nucleus matrix
Chromosome
Cytoplasm, cell cortex
Cell membrane
; Lipid-anchor
Lateral cell membrane
Note: Mitotic cell cycle-dependent shuttling protein that relocalizes from the interphase nucleus to the spindle poles and cell cortex (PubMed:19255246, PubMed:24109598, PubMed:26765568).
The localization to the spindle poles is regulated by AAAS (By similarity).
In interphase, resides in the nuclear matrix (PubMed:19255246).
In prophase, restricted to the interchromatin or condensed chromosome space. 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. Translocates from the spindle midzone towards the spindle poles along spindle fibers in a MT- and dynein-dynactin-dependent manner until the anaphase onset (By similarity).
In metaphase, recruited to the polar cortical region in a GPSM2- and GNAI1-dependent manner (PubMed:24109598).
Excluded from the metaphase equatorial cortical region in a RanGTP-dependent manner. Phosphorylation on Thr-2037 by CDK1 results in its localization at spindle poles in metaphase, but not at the cell cortex (By similarity).
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:24109598).
Excluded from the anaphase equatorial region of the cell cortex in a RACGAP1- and KIF23-dependent and RanGTP-independent manner. Associated with astral MTs emanating from the spindle poles during anaphase. Nonphosphorylated Thr-2037 localizes at the cell cortex, weakly during metaphase and more prominently during anaphase in a phosphatase PPP2CA-dependent manner. As mitosis progresses it reassociates with telophase chromosomes very early during nuclear reformation, before substantial accumulation of lamins on chromosomal surfaces is evident. Localizes to the tips of cortical MTs in prometaphase (By similarity).
Localizes along MTs and specifically to both MT plus and minus ends (PubMed:26765568).
Accumulates also at MT tips near the cell periphery. Colocalizes with GPSM2 at mitotic spindle poles during mitosis. Colocalizes with SPAG5 at mitotic spindle at prometaphase and at mitotic spindle poles at metaphase and anaphase. Colocalizes with ABRO1 at mitotic spindle poles. Colocalized with TNKS from prophase through to anaphase in mitosis. Colocalizes with tubulin alpha. CCSAP is essential for its centrosomal localization (By similarity).
In horizontally retinal progenitor dividing cells, localized to the lateral cortical region (PubMed:26766442).

Keywords

Phenotypes & Variants

Disruption phenotype

Mutant mice with an internal in-frame deletion of exon 22 exhibit early embryonic lethality (PubMed:19255246).
Mutant mice with a conditional internal in-frame deletion of exon 22 show embryonic lethality and display inhibition of primary embryonic fibroblast proliferation that display mitotic centrosome-spindle coupling, microtubule-focusing at the spindle poles and equatorial metaphase chromosome alignement defects (PubMed:19255246).
Mutant mice with a conditional internal in-frame deletion of exon 22 in the embryonic epidermis show neonatal lethality and display perturbation of epidermis differentiation characterized by increased suprabasal cell divisions and mitotic spindle orientation defects (PubMed:26765568).
Adult mutant mice with a conditional internal in-frame deletion of exon 22 in interfollicular and hair follicles display an almost complete absence of hair regrowth and mitotic spindle orientation defects in hair follicle matrix cells (PubMed:26765568).

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 118 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue, cross-link, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00004408791-2094Nuclear mitotic apparatus protein 1
Modified residue160Phosphoserine
Modified residue161Phosphothreonine
Modified residue167Phosphoserine
Modified residue201Phosphoserine
Modified residue209Phosphothreonine
Modified residue269Phosphoserine
Modified residue377N6-acetyllysine
Modified residue386Phosphoserine
Modified residue398Phosphoserine
Modified residue443N6-acetyllysine
Modified residue878N6-acetyllysine
Modified residue1183Phosphoserine
Modified residue1221Phosphoserine
Modified residue1507N6-acetyllysine
Modified residue1583Phosphoserine
Cross-link1681Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue1703Phosphoserine
Modified residue1706Phosphoserine
Modified residue1710Phosphoserine
Modified residue1739Phosphoserine
Modified residue1742Phosphoserine
Cross-link1748Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate
Cross-link1748Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Modified residue1751Phosphoserine
Modified residue1754Phosphoserine; by PLK1
Modified residue1756Phosphotyrosine
Modified residue1758Phosphothreonine
Modified residue1771Phosphoserine; by PLK1
Modified residue1774Phosphoserine
Modified residue1782Phosphoserine
Modified residue1786Phosphothreonine
Cross-link1804Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue1812Phosphoserine
Modified residue1815Phosphoserine
Modified residue1816Phosphoserine; by PLK1
Modified residue1818Phosphotyrosine
Modified residue1822Phosphoserine
Modified residue1826Phosphoserine; alternate
Glycosylation1826O-linked (GlcNAc) serine; alternate
Modified residue1844Phosphoserine
Modified residue1869Phosphoserine
Modified residue1951Phosphoserine
Modified residue1973Phosphoserine
Modified residue1974Phosphoserine
Modified residue1982Phosphothreonine
Modified residue1985Phosphoserine
Modified residue1997Phosphothreonine; by CDK1
Modified residue2029Phosphoserine
Modified residue2037Phosphothreonine
Modified residue2044Phosphoserine
Modified residue2059Phosphoserine
Modified residue2069Phosphoserine; by CDK1
Modified residue2085Phosphothreonine; by CDK1

Post-translational modification

Phosphorylation and dephosphorylation on Thr-2037 regulates the extent of cortical NUMA1 and the dynein-dynactin complex localization during mitotic metaphase and anaphase. In metaphase, phosphorylation on Thr-2037 occurs in a kinase CDK1-dependent manner; this phosphorylation maintains low levels of cortical dynein-dynactin complex at metaphase, and hence proper spindle positioning. In anaphase, dephosphorylated on Thr-2037 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. Probably also phosphorylated on Thr-1997 and Ser-2069 by CDK1; these phosphorylations may regulate its cell cortex recruitment during metaphase and anaphase. Phosphorylated on Ser-1751, Ser-1754, Ser-1771 and Ser-1816 by PLK1; these phosphorylations induce cortical dynein-dynactin complex dissociation from the NUMA1-GPSM2 complex and negatively regulates cortical dynein-dynactin complex localization.
ADP-ribosylated by TNKS at the onset of mitosis; ADP-ribosylation is not required for its localization to spindle poles.
O-glycosylated during cytokinesis at sites identical or close to phosphorylation sites, this interferes with the phosphorylation status.
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.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in testis, speen, liver, lung, spinal cord and brain. Expressed in Purkinje neurons (at protein level) (PubMed:19255246).

Gene expression databases

Interaction

Subunit

Homodimer. Also forms multiarm oligomers by association of C-terminal tail domains, oligomers may further assemble to form a hexagonal nuclear lattice-like network. 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. Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (By similarity).
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. 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. 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. Does not interact with GPSM2 during anaphase. Interacts (via C-terminus) with the nuclear importin alpha/importin beta receptor; this interaction is inhibited by RanGTP. Interacts (via C-terminus) with KPNB1; this interaction is inhibited by RanGTP and the BRISC complex. Interacts with ABRAXAS2 and the BRISC complex; these interactions regulate mitotic spindle assembly. Interacts (via N-terminal end of the coiled-coil domain) with RAE1; this interaction promotes mitotic spindle formation. 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. Interacts with TNKS; this interaction occurs at the onset of mitosis. Interacts with TNKS2. Interacts with tubulin. Interacts with KHDC3 (via C-terminus) (PubMed:25936915).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, coiled coil, compositional bias, motif.

TypeIDPosition(s)Description
Region1-210Head (Globular)
Coiled coil211-1681
Region617-636Disordered
Region723-759Disordered
Region921-1000Disordered
Region1081-1143Disordered
Compositional bias1126-1143Polar residues
Region1173-1223Disordered
Compositional bias1191-1213Basic and acidic residues
Region1681-1858Membrane-binding domain 1
Region1682-2094Tail (Globular)
Region1718-1743Disordered
Compositional bias1720-1738Polar residues
Motif1724-1730Tankyrase-binding domain
Region1760-1795Disordered
Region1770-17924.1-binding domain
Region1807-1883Disordered
Compositional bias1812-1844Polar residues
Compositional bias1855-1883Polar residues
Region1864-1967Tubulin-binding domain
Region1874-1908GPSM2-binding domain
Region1937-2094Disordered
Compositional bias1958-1985Polar residues
Region1963-2042Membrane-binding domain 2
Motif1966-1971Nuclear localization signal
Compositional bias1996-2010Basic and acidic residues
Compositional bias2057-2084Polar residues

Domain

The C-terminal tubulin-binding domain mediates direct binding to microtubules, independently of dynein-dynactin complex, and induces their bundling and stabilization. The 4.1-binding domain is necessary for its cortical stability and spindle orientation.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    2,094
  • Mass (Da)
    235,630
  • Last updated
    2011-04-05 v1
  • Checksum
    09074ACC3A6A1046
MTLHATRAATLLSWVNSLHVADPVETVLQLQDCSIFIKIINTIHDTKEGQQILQQPLPERLDFVCSFLQKNRKHPSSTQCLVSVQKVIEGSEMELAKMIMLFLYQSTMSSRNLRDWEQFEYGVQAELAVILKFMLDHEESLNLTEDLESFLEKVPYTHASTLSEELSPPSHQTKRKIRFLEIQRIASSSSENNFLSGSPSSPMGDILQTPQFQMRRLKKQLADERSNRDDLELELSESLKLLTEKDAQIAMMQQRIDHLALLNEKQAASSQEPSELEELRGKNESLTVRLHETLKQCQNLKTEKSQMDRKISQLSEENGDLSFKVREFANHLQQLQGAFNDLIEEHSKASQEWAEKQARLENELSTALQDKKCLEEKNEILQGKLSQLEDQATRLQESPAPEKGEVLGDALQLDTLKQEAAKLATDNTQLQTRVETLECERGKQEAQLLAERSRFEDEKQQLASLIADLQSSVSNLSQAKEELEQASQAQGAQLTAQLTSMTGLNATLQQRDQELASLKEQAKKEQAQMLQTMQEQEQAAQGLRQQVEQLSSSLKLKEQQLEEAAKEQEATRQDHAQQLAIVAEAREASLRERDTARQQLETVEKEKDAKLESLQQQLQAANDARDNAQTSVTQAQQEKAELSQKIGELHACIEASHQEQRQVQARVTELEAQLKAEQQKTTEREKVVQEKAQLQEQLRALEESLKITKGSLEEEKRRAADALKEQQCRATEMEAESRSLMEQREREQKELEQEKAGRKGLEARIQQLEEAHQAETEALRHELAEATASQHRAESECERLIREVESRQKRFEARQQEEARYGAMFQEQLMALKGEKTGQEVQEEAVEIHSEGQPGQQQSQLAQLHASLAKAIQQVQEKEVRAQKLVDDLSALQEKMAATNKEVACLKTLVLKAGEQQETASLELLKEPPRAANRASDQLGEQQGRPFSSTHAAVKAMEREAEQMGGELERLRAALIKSQGQQQEERGQQEREVARLTQERGQAQADLAQEKAAKAELEMRLQNTLNEQRVEFAALQEALAHALTEKEGTDQELAKLRGQEAAQRTELKELQQTLEQLKIQLVKKEKEHPAGGASGEDASGPGTQSETAGKTDAPGPELQALRAEISKLEQQCQQQQQQVEGLTHSLKSERACRAEQDKALETLQGQLEEKARELGHNQAASASAQRELQALRAKAQDHSKAEEEWKAQVARGQQEAERKSSLISSLEEEVSILNRQVLEKEGESKELKRLVVAESEKSQKLEERLRLLQVETASNSARAAERSSALREEVQSLREEVEKQRVVSENSRQELASQAERAEELGQELKAWQEKFFQKEQALSALQLEHTSTQALVSELLPAKHLCQQLQAEQAAAEKRFREELEQSKQAAGGLQAELMRAQRELGELGSLRQKIVEQERAAQQLRAEKASYAEQLSMLKKAHGLLAEENRGLGERANLGRQFLEVELDQAREKYVQELAAVRTDAETHLAEMRQEAQSTSRELEVMTAKYEGAKVKVLEERQRFQEERQKLTAQVEELSKKLTEHDQASKVQQQKLKAFQAQRGESQQEVQRLQTQLNELQAQLSQKEQAAEHYKLQMEKAKTHYDAKKQQNQKLQEQLQDLEELQKENKELRSEAERLGRELQQAGLKTKEAEQTCRHLTAQVRSLEAQVAHADQQLRDLGKFQVATDALKSREPQVKPQLDLSIDSLDLSLEEGTPCSVASKLPRTQPDGTSVPGEPASPISQRLPPKVESLESLYFTPTPARGQAPLETSLDSLGDAFPDSGRKTRSARRRTTQIINITMTKKLELEEPDSANSSFYSTQSAPASQANLRATSSTQSLARLGSPDDGNSALLSLPGYRPTTRSSARRSQARMSSGAPQGRNSFYMGTCQDEPEQLDDWNRIAELQQRNRVCPPHLKTCYPLESRPTLSLATITDEEMKTGDPRETLRRASMQPAQIAEGVGITTRQQRKRVSSETHQGPGTPESKKATSCFPRPMTPRDRHEGRKQSSTADTQKKAAPVLKQADRRQSMAFSILNTPKKLGNSLLRRGASKKTPAKVSPNPRSGTRRSPRIATTTTGTATVATTPRAKGKVKH

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
F6ZQA3F6ZQA3_MOUSENuma1741
A0A1B0GT38A0A1B0GT38_MOUSENuma1207
A0A1B0GT61A0A1B0GT61_MOUSENuma1875
A0A1B0GSH2A0A1B0GSH2_MOUSENuma1218
A0A1B0GSW3A0A1B0GSW3_MOUSENuma11082

Features

Showing features for sequence conflict, compositional bias.

TypeIDPosition(s)Description
Sequence conflict539in Ref. 2; AAH49791
Compositional bias1126-1143Polar residues
Compositional bias1191-1213Basic and acidic residues
Compositional bias1720-1738Polar residues
Compositional bias1812-1844Polar residues
Compositional bias1855-1883Polar residues
Compositional bias1958-1985Polar residues
Compositional bias1996-2010Basic and acidic residues
Compositional bias2057-2084Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AC167240
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC049791
EMBL· GenBank· DDBJ
AAH49791.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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