NUMBL_MOUSE
ID NUMBL_MOUSE Reviewed; 604 AA.
AC O08919; Q4QQQ2; Q6NVG8;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Numb-like protein;
GN Name=Numbl; Synonyms=Nbl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=9169836; DOI=10.1242/dev.124.10.1887;
RA Zhong W., Jiang M.-M., Weinmaster G., Jan L.Y., Jan Y.N.;
RT "Differential expression of mammalian Numb, Numblike and Notch1 suggests
RT distinct roles during mouse cortical neurogenesis.";
RL Development 124:1887-1897(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=12410312; DOI=10.1038/nature01124;
RA Petersen P.H., Zou K., Hwang J.K., Jan Y.N., Zhong W.;
RT "Progenitor cell maintenance requires numb and numblike during mouse
RT neurogenesis.";
RL Nature 419:929-934(2002).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=15273690; DOI=10.1038/nn1289;
RA Petersen P.H., Zou K., Krauss S., Zhong W.;
RT "Continuing role for mouse Numb and Numbl in maintaining progenitor cells
RT during cortical neurogenesis.";
RL Nat. Neurosci. 7:803-811(2004).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17174898; DOI=10.1016/j.cell.2006.10.041;
RA Kuo C.T., Mirzadeh Z., Soriano-Navarro M., Rasin M., Wang D., Shen J.,
RA Sestan N., Garcia-Verdugo J., Alvarez-Buylla A., Jan L.Y., Jan Y.N.;
RT "Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity
RT in the subventricular neurogenic niche.";
RL Cell 127:1253-1264(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Plays a role in the process of neurogenesis. Required
CC throughout embryonic neurogenesis to maintain neural progenitor cells,
CC also called radial glial cells (RGCs), by allowing their daughter cells
CC to choose progenitor over neuronal cell fate. Not required for the
CC proliferation of neural progenitor cells before the onset of embryonic
CC neurogenesis. Also required postnatally in the subventricular zone
CC (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal
CC wall integrity. Negative regulator of NF-kappa-B signaling pathway. The
CC inhibition of NF-kappa-B activation is mediated at least in part, by
CC preventing MAP3K7IP2 to interact with polyubiquitin chains of TRAF6 and
CC RIPK1 and by stimulating the 'Lys-48'-linked polyubiquitination and
CC degradation of TRAF6 in cortical neurons. {ECO:0000269|PubMed:12410312,
CC ECO:0000269|PubMed:15273690, ECO:0000269|PubMed:17174898,
CC ECO:0000269|PubMed:9169836}.
CC -!- SUBUNIT: Interacts (via PTB domain) with MAP3K7IP2 (via C-terminal).
CC Interacts (via C-terminal) with TRAF6 (via TRAF domains) (By
CC similarity). Associates with EPS15 and NOTCH1. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9169836}.
CC Note=Symmetrically distributed throughout the cytoplasm in non dividing
CC neuroblasts of the CNS.
CC -!- TISSUE SPECIFICITY: Preferentially expressed in the nervous system. In
CC the developing neocortex, expressed in postmitotic neurons in the
CC cortical plate but not in progenitors within the ventricular zone.
CC {ECO:0000269|PubMed:9169836}.
CC -!- DEVELOPMENTAL STAGE: Expressed in neural progenitor and neuron cells
CC throughout the developing nervous system. Expressed in somites and
CC throughout the neural tube from 8.5 dpc, onward.
CC {ECO:0000269|PubMed:12410312, ECO:0000269|PubMed:15273690,
CC ECO:0000269|PubMed:9169836}.
CC -!- DOMAIN: The PTB domain is necessary for the inhibition of MAP3K7IP2-
CC mediated activation of NF-kappa-B. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mutants are viable and
CC fertile. Mice lacking both Numb and Numbl genes die around 9.5 dpc,
CC with severe defects in somite and vasculature formation, neuronal tube
CC closure and axial turning. Conditional double-knockout (cdKO) mutants
CC (Numb and Numbl genes), with expression abrogated in neural progenitor
CC cells from 8.5 dpc (just before the onset of neurogenesis), display a
CC loss of neural progenitor cells formation and an overexpression of
CC neurons as neurogenesis progresses; cdKO mutants become necrotic at
CC 12.5 dpc and die around this stage. Conditional double-knockout (cdKO)
CC mutants (Numb and Numbl genes), with expression abrogated in neural
CC progenitor cells from 10.5 dpc (just after the onset of neurogenesis),
CC display a premature depletion of neural progenitor cells in the dorsal
CC forebrain ventrical zone of the neocortex and in the hippocampal CA
CC fields as neurogenesis progresses; cdKO mutants are viable and fertile,
CC but showed a reduction in the thickness of the neocortex and the
CC hippocampus and an enlargement of the lateral ventricles. Tamoxifen-
CC inducible double-knockout (cdKO) mutants (Numb and Numbl genes), with
CC expression abrogated postnatally in the subventricular zone (SVZ)
CC neuroprogenitors and in ependymal cells, display a loss of SVZ
CC neuroblasts and show a disorganized ependyma lacking both
CC interdigitation junction between neighboring cells and increasing
CC number of separated cells. {ECO:0000269|PubMed:12410312,
CC ECO:0000269|PubMed:15273690, ECO:0000269|PubMed:17174898}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U96441; AAB58697.1; -; mRNA.
DR EMBL; CH466593; EDL24192.1; -; Genomic_DNA.
DR EMBL; BC068116; AAH68116.1; -; mRNA.
DR EMBL; BC098097; AAH98097.1; -; mRNA.
DR CCDS; CCDS21016.1; -.
DR RefSeq; NP_035080.2; NM_010950.2.
DR AlphaFoldDB; O08919; -.
DR SMR; O08919; -.
DR BioGRID; 201878; 5.
DR IntAct; O08919; 3.
DR STRING; 10090.ENSMUSP00000078245; -.
DR iPTMnet; O08919; -.
DR PhosphoSitePlus; O08919; -.
DR EPD; O08919; -.
DR jPOST; O08919; -.
DR MaxQB; O08919; -.
DR PaxDb; O08919; -.
DR PeptideAtlas; O08919; -.
DR PRIDE; O08919; -.
DR ProteomicsDB; 295465; -.
DR Antibodypedia; 30612; 272 antibodies from 32 providers.
DR DNASU; 18223; -.
DR Ensembl; ENSMUST00000079258; ENSMUSP00000078245; ENSMUSG00000063160.
DR GeneID; 18223; -.
DR KEGG; mmu:18223; -.
DR UCSC; uc009fvq.1; mouse.
DR CTD; 9253; -.
DR MGI; MGI:894702; Numbl.
DR VEuPathDB; HostDB:ENSMUSG00000063160; -.
DR eggNOG; KOG3537; Eukaryota.
DR GeneTree; ENSGT00940000160957; -.
DR HOGENOM; CLU_031797_1_1_1; -.
DR InParanoid; O08919; -.
DR OMA; YPPMPQV; -.
DR OrthoDB; 1110016at2759; -.
DR PhylomeDB; O08919; -.
DR TreeFam; TF314159; -.
DR BioGRID-ORCS; 18223; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Numbl; mouse.
DR PRO; PR:O08919; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O08919; protein.
DR Bgee; ENSMUSG00000063160; Expressed in dentate gyrus of hippocampal formation granule cell and 193 other tissues.
DR Genevisible; O08919; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0034332; P:adherens junction organization; IGI:MGI.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0021670; P:lateral ventricle development; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0021849; P:neuroblast division in subventricular zone; IMP:UniProtKB.
DR GO; GO:0007405; P:neuroblast proliferation; IGI:MGI.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; ISO:MGI.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:0019538; P:protein metabolic process; ISS:UniProtKB.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR016698; Numb/numb-like.
DR InterPro; IPR010449; Numb_domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR PANTHER; PTHR47368; PTHR47368; 1.
DR Pfam; PF06311; NumbF; 1.
DR Pfam; PF00640; PID; 1.
DR PIRSF; PIRSF017607; Numb/numb-like; 1.
DR SMART; SM00462; PTB; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Developmental protein; Neurogenesis; Phosphoprotein;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..604
FT /note="Numb-like protein"
FT /id="PRO_0000058000"
FT DOMAIN 74..225
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 223..283
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..457
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 531..604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..68
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 422..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 537..568
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R0"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R0"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R0"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R0"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 28
FT /note="P -> A (in Ref. 1; AAB58697)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="Missing (in Ref. 1; AAB58697)"
FT /evidence="ECO:0000305"
FT CONFLICT 589
FT /note="S -> F (in Ref. 3; AAH68116)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 604 AA; 64130 MW; 3DD012B7BB30987E CRC64;
MSRSAAASGG PRRPDQHLSP APCGASGPPE TFRTESDGAG TMNKLRQSLR RRKPAYVPEA
SRPHQWQADE DAVRKGTCSF PVRYLGHVEV EESRGMHVCE DAVKKLKAMG RKSVKSVLWV
SADGLRVVDD KTKDLLVDQT IEKVSFCAPD RNLDKAFSYI CRDGTTRRWI CHCFLALKDS
GERLSHAVGC AFAACLERKQ RREKECGVTA AFDASRTSFA REGSFRLSGG GRPAEREAGD
KKKAEAAAAP AVAPGPAQPG HVSPTPATTS PGEKGEAGTP VAAGTTAAAI PRRHAPLEQL
VRQGSFRGFP ALSQKNSPFK RQLSLRLNEL PSTLQRRTDF QVKGTVPEME PPGTGDSDGI
NALCTQISSS FASAGAPASG PPPATTGTSA WGEPSVPAAA AFQPGHKRTP SEAERWLEEV
SQVAKAQQQQ QQQQQQQQQQ QATSVPPMPT MAPTLQPFSA PVGPFDTAAA QVAVFLPPTH
MQPPFVPAYP GLGYPPMPRV PVVGITPSQM VANAFCSAAQ LQPQPATLLG KAGAFPPPAA
PSAPGGQARP RPNGAPWPPE PAPAPAPELD PFEAQWAALE GKPAVEKPSN PFSGDLQKTF
EIEL
