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Protein

Nuclear mitotic apparatus protein 1

Gene

Numa1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processCell cycle, Cell division, Chromosome partition, Mitosis
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-MMU-380320. Recruitment of NuMA to mitotic centrosomes.
R-MMU-68875. Mitotic Prophase.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear mitotic apparatus protein 1By similarity
Alternative name(s):
Nuclear mitotic apparatus proteinBy similarity
Short name:
NuMA proteinBy similarity
Gene namesi
Name:Numa1Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2443665. Numa1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Chromosome, Cytoplasm, Cytoskeleton, Membrane, Microtubule, Nucleus

Pathology & Biotechi

Disruption phenotypei

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).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004408791 – 2094Nuclear mitotic apparatus protein 1Add BLAST2094

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei160PhosphoserineBy similarity1
Modified residuei161PhosphothreonineBy similarity1
Modified residuei167PhosphoserineBy similarity1
Modified residuei201PhosphoserineBy similarity1
Modified residuei209PhosphothreonineBy similarity1
Modified residuei269PhosphoserineBy similarity1
Modified residuei377N6-acetyllysineBy similarity1
Modified residuei386PhosphoserineBy similarity1
Modified residuei398PhosphoserineCombined sources1
Modified residuei443N6-acetyllysineCombined sources1
Modified residuei878N6-acetyllysineBy similarity1
Modified residuei1183PhosphoserineBy similarity1
Modified residuei1221PhosphoserineBy similarity1
Modified residuei1507N6-acetyllysineBy similarity1
Modified residuei1583PhosphoserineBy similarity1
Cross-linki1681Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1703PhosphoserineCombined sources1
Modified residuei1706PhosphoserineCombined sources1
Modified residuei1710PhosphoserineBy similarity1
Modified residuei1739PhosphoserineCombined sources1
Modified residuei1742PhosphoserineBy similarity1
Cross-linki1748Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki1748Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1751PhosphoserineCombined sources1
Modified residuei1754Phosphoserine; by PLK1By similarity1
Modified residuei1756PhosphotyrosineBy similarity1
Modified residuei1758PhosphothreonineBy similarity1
Modified residuei1771Phosphoserine; by PLK1By similarity1
Modified residuei1774PhosphoserineBy similarity1
Modified residuei1782PhosphoserineCombined sources1
Modified residuei1786PhosphothreonineBy similarity1
Cross-linki1804Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1812PhosphoserineBy similarity1
Modified residuei1815PhosphoserineBy similarity1
Modified residuei1816Phosphoserine; by PLK1By similarity1
Modified residuei1818PhosphotyrosineBy similarity1
Modified residuei1822PhosphoserineBy similarity1
Modified residuei1826Phosphoserine; alternateBy similarity1
Glycosylationi1826O-linked (GlcNAc) serine; alternateBy similarity1
Modified residuei1844PhosphoserineCombined sources1
Modified residuei1869PhosphoserineBy similarity1
Modified residuei1951PhosphoserineCombined sources1
Modified residuei1973PhosphoserineBy similarity1
Modified residuei1974PhosphoserineCombined sources1
Modified residuei1982PhosphothreonineBy similarity1
Modified residuei1985PhosphoserineBy similarity1
Modified residuei1997Phosphothreonine; by CDK1By similarity1
Modified residuei2029PhosphoserineCombined sources1
Modified residuei2037PhosphothreonineCombined sources1
Modified residuei2044PhosphoserineBy similarity1
Modified residuei2059PhosphoserineBy similarity1
Modified residuei2069Phosphoserine; by CDK1By similarity1
Modified residuei2085Phosphothreonine; by CDK1By similarity1

Post-translational modificationi

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.By similarity
ADP-ribosylated by TNKS at the onset of mitosis; ADP-ribosylation is not required for its localization to spindle poles.By similarity
O-glycosylated during cytokinesis at sites identical or close to phosphorylation sites, this interferes with the phosphorylation status.By similarity
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.By similarity

Keywords - PTMi

Acetylation, ADP-ribosylation, Glycoprotein, Isopeptide bond, Lipoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiE9Q7G0.
PaxDbiE9Q7G0.
PeptideAtlasiE9Q7G0.
PRIDEiE9Q7G0.

PTM databases

iPTMnetiE9Q7G0.
PhosphoSitePlusiE9Q7G0.

Expressioni

Tissue specificityi

Expressed in testis, speen, liver, lung, spinal cord and brain. Expressed in Purkinje neurons (at protein level) (PubMed:19255246).1 Publication

Gene expression databases

BgeeiENSMUSG00000066306.
ExpressionAtlasiE9Q7G0. baseline and differential.
GenevisibleiE9Q7G0. MM.

Interactioni

Subunit structurei

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.By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiE9Q7G0. 1 interactor.
MINTiMINT-1867590.
STRINGi10090.ENSMUSP00000081912.

Structurei

3D structure databases

SMRiE9Q7G0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 210Head (Globular)By similarityAdd BLAST210
Regioni1681 – 1858Membrane-binding domain 1By similarityAdd BLAST178
Regioni1682 – 2094Tail (Globular)By similarityAdd BLAST413
Regioni1770 – 17924.1-binding domainBy similarityAdd BLAST23
Regioni1864 – 1967Tubulin-binding domainBy similarityAdd BLAST104
Regioni1874 – 1908GPSM2-binding domainBy similarityAdd BLAST35
Regioni1963 – 2042Membrane-binding domain 2By similarityAdd BLAST80

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili211 – 1681Sequence analysisAdd BLAST1471

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1724 – 1730Tankyrase-binding domainBy similarity7
Motifi1966 – 1971Nuclear localization signalBy similarity6

Domaini

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.By similarity

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IFJ8. Eukaryota.
ENOG41125FF. LUCA.
GeneTreeiENSGT00730000111158.
HOGENOMiHOG000113889.
HOVERGENiHBG052694.
InParanoidiE9Q7G0.
KOiK16808.
OMAiQGRQFCS.
OrthoDBiEOG091G00XV.
TreeFamiTF334442.

Family and domain databases

InterProiView protein in InterPro
IPR026650. NUMA1.
PANTHERiPTHR18902:SF24. PTHR18902:SF24. 1 hit.

Sequencei

Sequence statusi: Complete.

E9Q7G0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTLHATRAAT LLSWVNSLHV ADPVETVLQL QDCSIFIKII NTIHDTKEGQ
60 70 80 90 100
QILQQPLPER LDFVCSFLQK NRKHPSSTQC LVSVQKVIEG SEMELAKMIM
110 120 130 140 150
LFLYQSTMSS RNLRDWEQFE YGVQAELAVI LKFMLDHEES LNLTEDLESF
160 170 180 190 200
LEKVPYTHAS TLSEELSPPS HQTKRKIRFL EIQRIASSSS ENNFLSGSPS
210 220 230 240 250
SPMGDILQTP QFQMRRLKKQ LADERSNRDD LELELSESLK LLTEKDAQIA
260 270 280 290 300
MMQQRIDHLA LLNEKQAASS QEPSELEELR GKNESLTVRL HETLKQCQNL
310 320 330 340 350
KTEKSQMDRK ISQLSEENGD LSFKVREFAN HLQQLQGAFN DLIEEHSKAS
360 370 380 390 400
QEWAEKQARL ENELSTALQD KKCLEEKNEI LQGKLSQLED QATRLQESPA
410 420 430 440 450
PEKGEVLGDA LQLDTLKQEA AKLATDNTQL QTRVETLECE RGKQEAQLLA
460 470 480 490 500
ERSRFEDEKQ QLASLIADLQ SSVSNLSQAK EELEQASQAQ GAQLTAQLTS
510 520 530 540 550
MTGLNATLQQ RDQELASLKE QAKKEQAQML QTMQEQEQAA QGLRQQVEQL
560 570 580 590 600
SSSLKLKEQQ LEEAAKEQEA TRQDHAQQLA IVAEAREASL RERDTARQQL
610 620 630 640 650
ETVEKEKDAK LESLQQQLQA ANDARDNAQT SVTQAQQEKA ELSQKIGELH
660 670 680 690 700
ACIEASHQEQ RQVQARVTEL EAQLKAEQQK TTEREKVVQE KAQLQEQLRA
710 720 730 740 750
LEESLKITKG SLEEEKRRAA DALKEQQCRA TEMEAESRSL MEQREREQKE
760 770 780 790 800
LEQEKAGRKG LEARIQQLEE AHQAETEALR HELAEATASQ HRAESECERL
810 820 830 840 850
IREVESRQKR FEARQQEEAR YGAMFQEQLM ALKGEKTGQE VQEEAVEIHS
860 870 880 890 900
EGQPGQQQSQ LAQLHASLAK AIQQVQEKEV RAQKLVDDLS ALQEKMAATN
910 920 930 940 950
KEVACLKTLV LKAGEQQETA SLELLKEPPR AANRASDQLG EQQGRPFSST
960 970 980 990 1000
HAAVKAMERE AEQMGGELER LRAALIKSQG QQQEERGQQE REVARLTQER
1010 1020 1030 1040 1050
GQAQADLAQE KAAKAELEMR LQNTLNEQRV EFAALQEALA HALTEKEGTD
1060 1070 1080 1090 1100
QELAKLRGQE AAQRTELKEL QQTLEQLKIQ LVKKEKEHPA GGASGEDASG
1110 1120 1130 1140 1150
PGTQSETAGK TDAPGPELQA LRAEISKLEQ QCQQQQQQVE GLTHSLKSER
1160 1170 1180 1190 1200
ACRAEQDKAL ETLQGQLEEK ARELGHNQAA SASAQRELQA LRAKAQDHSK
1210 1220 1230 1240 1250
AEEEWKAQVA RGQQEAERKS SLISSLEEEV SILNRQVLEK EGESKELKRL
1260 1270 1280 1290 1300
VVAESEKSQK LEERLRLLQV ETASNSARAA ERSSALREEV QSLREEVEKQ
1310 1320 1330 1340 1350
RVVSENSRQE LASQAERAEE LGQELKAWQE KFFQKEQALS ALQLEHTSTQ
1360 1370 1380 1390 1400
ALVSELLPAK HLCQQLQAEQ AAAEKRFREE LEQSKQAAGG LQAELMRAQR
1410 1420 1430 1440 1450
ELGELGSLRQ KIVEQERAAQ QLRAEKASYA EQLSMLKKAH GLLAEENRGL
1460 1470 1480 1490 1500
GERANLGRQF LEVELDQARE KYVQELAAVR TDAETHLAEM RQEAQSTSRE
1510 1520 1530 1540 1550
LEVMTAKYEG AKVKVLEERQ RFQEERQKLT AQVEELSKKL TEHDQASKVQ
1560 1570 1580 1590 1600
QQKLKAFQAQ RGESQQEVQR LQTQLNELQA QLSQKEQAAE HYKLQMEKAK
1610 1620 1630 1640 1650
THYDAKKQQN QKLQEQLQDL EELQKENKEL RSEAERLGRE LQQAGLKTKE
1660 1670 1680 1690 1700
AEQTCRHLTA QVRSLEAQVA HADQQLRDLG KFQVATDALK SREPQVKPQL
1710 1720 1730 1740 1750
DLSIDSLDLS LEEGTPCSVA SKLPRTQPDG TSVPGEPASP ISQRLPPKVE
1760 1770 1780 1790 1800
SLESLYFTPT PARGQAPLET SLDSLGDAFP DSGRKTRSAR RRTTQIINIT
1810 1820 1830 1840 1850
MTKKLELEEP DSANSSFYST QSAPASQANL RATSSTQSLA RLGSPDDGNS
1860 1870 1880 1890 1900
ALLSLPGYRP TTRSSARRSQ ARMSSGAPQG RNSFYMGTCQ DEPEQLDDWN
1910 1920 1930 1940 1950
RIAELQQRNR VCPPHLKTCY PLESRPTLSL ATITDEEMKT GDPRETLRRA
1960 1970 1980 1990 2000
SMQPAQIAEG VGITTRQQRK RVSSETHQGP GTPESKKATS CFPRPMTPRD
2010 2020 2030 2040 2050
RHEGRKQSST ADTQKKAAPV LKQADRRQSM AFSILNTPKK LGNSLLRRGA
2060 2070 2080 2090
SKKTPAKVSP NPRSGTRRSP RIATTTTGTA TVATTPRAKG KVKH
Length:2,094
Mass (Da):235,630
Last modified:April 5, 2011 - v1
Checksum:i09074ACC3A6A1046
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti539A → V in AAH49791 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC167240 Genomic DNA. No translation available.
BC049791 mRNA. Translation: AAH49791.1.
CCDSiCCDS40046.1.
RefSeqiNP_598708.3. NM_133947.3.
XP_006507240.1. XM_006507177.2.
UniGeneiMm.27259.

Genome annotation databases

EnsembliENSMUST00000084852; ENSMUSP00000081912; ENSMUSG00000066306.
GeneIDi101706.
KEGGimmu:101706.
UCSCiuc009ipz.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiNUMA1_MOUSE
AccessioniPrimary (citable) accession number: E9Q7G0
Secondary accession number(s): Q80Y35
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2017
Last sequence update: April 5, 2011
Last modified: November 22, 2017
This is version 58 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot