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Protein

Numb-like protein

Gene

Numbl

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

Functioni

Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of embryonic neurogenesis. Also required postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. Negative regulator of NF-kappa-B signaling pathway. The inhibition of NF-kappa-B activation is mediated at least in part, by preventing MAP3K7IP2 to interact with polyubiquitin chains of TRAF6 and RIPK1 and by stimulating the 'Lys-48'-linked polyubiquitination and degradation of TRAF6 in cortical neurons.4 Publications

GO - Biological processi

  • adherens junction organization Source: MGI
  • axonogenesis Source: MGI
  • cytokine-mediated signaling pathway Source: UniProtKB
  • forebrain development Source: MGI
  • lateral ventricle development Source: UniProtKB
  • nervous system development Source: MGI
  • neuroblast division in subventricular zone Source: UniProtKB
  • neuroblast proliferation Source: MGI
  • positive regulation of dendrite morphogenesis Source: Ensembl
  • positive regulation of neurogenesis Source: UniProtKB
  • protein metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Neurogenesis, Ubl conjugation pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Numb-like protein
Gene namesi
Name:Numbl
Synonyms:Nbl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:894702. Numbl.

Subcellular locationi

  • Cytoplasm 1 Publication

  • Note: Symmetrically distributed throughout the cytoplasm in non dividing neuroblasts of the CNS.

GO - Cellular componenti

  • cytoplasm Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mutants are viable and fertile. Mice lacking both Numb and Numbl genes die around 9.5 dpc, with severe defects in somite and vasculature formation, neuronal tube closure and axial turning. Conditional double-knockout (cdKO) mutants (Numb and Numbl genes), with expression abrogated in neural progenitor cells from 8.5 dpc (just before the onset of neurogenesis), display a loss of neural progenitor cells formation and an overexpression of neurons as neurogenesis progresses; cdKO mutants become necrotic at 12.5 dpc and die around this stage. Conditional double-knockout (cdKO) mutants (Numb and Numbl genes), with expression abrogated in neural progenitor cells from 10.5 dpc (just after the onset of neurogenesis), display a premature depletion of neural progenitor cells in the dorsal forebrain ventrical zone of the neocortex and in the hippocampal CA fields as neurogenesis progresses; cdKO mutants are viable and fertile, but showed a reduction in the thickness of the neocortex and the hippocampus and an enlargement of the lateral ventricles. Tamoxifene-inducible double-knockout (cdKO) mutants (Numb and Numbl genes), with expression abrogated postnatally in the subventricular zone (SVZ) neuroprogenitors and in ependymal cells, display a loss of SVZ neuroblasts and show a disorganized ependyma lacking both interdigitation junction between neighboring cells and increasing number of separated cells.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 604604Numb-like proteinPRO_0000058000Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei224 – 2241PhosphoserineBy similarity
Modified residuei228 – 2281PhosphoserineBy similarity
Modified residuei263 – 2631PhosphoserineBy similarity
Modified residuei279 – 2791PhosphothreonineBy similarity
Modified residuei411 – 4111PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO08919.
MaxQBiO08919.
PaxDbiO08919.
PeptideAtlasiO08919.
PRIDEiO08919.

PTM databases

iPTMnetiO08919.
PhosphoSiteiO08919.

Expressioni

Tissue specificityi

Preferentially expressed in the nervous system. In the developing neocortex, expressed in postmitotic neurons in the cortical plate but not in progenitors within the ventricular zone.1 Publication

Developmental stagei

Expressed in neural progenitor and neuron cells throughout the developing nervous system. Expressed in somites and throughout the neural tube from 8.5 dpc, onward.3 Publications

Gene expression databases

BgeeiO08919.
CleanExiMM_NUMBL.
GenevisibleiO08919. MM.

Interactioni

Subunit structurei

Interacts (via PTB domain) with MAP3K7IP2 (via C-terminal). Interacts (via C-terminal) with TRAF6 (via TRAF domains) (By similarity). Associates with EPS15 and NOTCH1.By similarity

Protein-protein interaction databases

BioGridi201878. 1 interaction.
IntActiO08919. 1 interaction.
STRINGi10090.ENSMUSP00000078245.

Structurei

3D structure databases

ProteinModelPortaliO08919.
SMRiO08919. Positions 60-202.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini74 – 225152PIDPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi422 – 44120Gln-richAdd
BLAST

Domaini

The PTB domain is necessary for the inhibition of MAP3K7IP2-mediated activation of NF-kappa-B.By similarity

Sequence similaritiesi

Contains 1 PID domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3537. Eukaryota.
ENOG410XT15. LUCA.
GeneTreeiENSGT00530000062937.
HOGENOMiHOG000220819.
HOVERGENiHBG006672.
InParanoidiO08919.
KOiK06057.
OMAiPEQHLPP.
OrthoDBiEOG7MKW5J.
TreeFamiTF314159.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR016698. Numb/numb-like.
IPR010449. Numb_domain.
IPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
[Graphical view]
PfamiPF06311. NumbF. 1 hit.
PF00640. PID. 1 hit.
[Graphical view]
PIRSFiPIRSF017607. Numb/numb-like. 1 hit.
SMARTiSM00462. PTB. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS01179. PID. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O08919-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRSAAASGG PRRPDQHLSP APCGASGPPE TFRTESDGAG TMNKLRQSLR
60 70 80 90 100
RRKPAYVPEA SRPHQWQADE DAVRKGTCSF PVRYLGHVEV EESRGMHVCE
110 120 130 140 150
DAVKKLKAMG RKSVKSVLWV SADGLRVVDD KTKDLLVDQT IEKVSFCAPD
160 170 180 190 200
RNLDKAFSYI CRDGTTRRWI CHCFLALKDS GERLSHAVGC AFAACLERKQ
210 220 230 240 250
RREKECGVTA AFDASRTSFA REGSFRLSGG GRPAEREAGD KKKAEAAAAP
260 270 280 290 300
AVAPGPAQPG HVSPTPATTS PGEKGEAGTP VAAGTTAAAI PRRHAPLEQL
310 320 330 340 350
VRQGSFRGFP ALSQKNSPFK RQLSLRLNEL PSTLQRRTDF QVKGTVPEME
360 370 380 390 400
PPGTGDSDGI NALCTQISSS FASAGAPASG PPPATTGTSA WGEPSVPAAA
410 420 430 440 450
AFQPGHKRTP SEAERWLEEV SQVAKAQQQQ QQQQQQQQQQ QATSVPPMPT
460 470 480 490 500
MAPTLQPFSA PVGPFDTAAA QVAVFLPPTH MQPPFVPAYP GLGYPPMPRV
510 520 530 540 550
PVVGITPSQM VANAFCSAAQ LQPQPATLLG KAGAFPPPAA PSAPGGQARP
560 570 580 590 600
RPNGAPWPPE PAPAPAPELD PFEAQWAALE GKPAVEKPSN PFSGDLQKTF

EIEL
Length:604
Mass (Da):64,130
Last modified:July 27, 2011 - v3
Checksum:i3DD012B7BB30987E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti28 – 281P → A in AAB58697 (PubMed:9169836).Curated
Sequence conflicti244 – 2441Missing in AAB58697 (PubMed:9169836).Curated
Sequence conflicti589 – 5891S → F in AAH68116 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U96441 mRNA. Translation: AAB58697.1.
CH466593 Genomic DNA. Translation: EDL24192.1.
BC068116 mRNA. Translation: AAH68116.1.
BC098097 mRNA. Translation: AAH98097.1.
CCDSiCCDS21016.1.
RefSeqiNP_035080.2. NM_010950.2.
UniGeneiMm.458153.

Genome annotation databases

EnsembliENSMUST00000079258; ENSMUSP00000078245; ENSMUSG00000063160.
GeneIDi18223.
KEGGimmu:18223.
UCSCiuc009fvq.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U96441 mRNA. Translation: AAB58697.1.
CH466593 Genomic DNA. Translation: EDL24192.1.
BC068116 mRNA. Translation: AAH68116.1.
BC098097 mRNA. Translation: AAH98097.1.
CCDSiCCDS21016.1.
RefSeqiNP_035080.2. NM_010950.2.
UniGeneiMm.458153.

3D structure databases

ProteinModelPortaliO08919.
SMRiO08919. Positions 60-202.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201878. 1 interaction.
IntActiO08919. 1 interaction.
STRINGi10090.ENSMUSP00000078245.

PTM databases

iPTMnetiO08919.
PhosphoSiteiO08919.

Proteomic databases

EPDiO08919.
MaxQBiO08919.
PaxDbiO08919.
PeptideAtlasiO08919.
PRIDEiO08919.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000079258; ENSMUSP00000078245; ENSMUSG00000063160.
GeneIDi18223.
KEGGimmu:18223.
UCSCiuc009fvq.1. mouse.

Organism-specific databases

CTDi9253.
MGIiMGI:894702. Numbl.

Phylogenomic databases

eggNOGiKOG3537. Eukaryota.
ENOG410XT15. LUCA.
GeneTreeiENSGT00530000062937.
HOGENOMiHOG000220819.
HOVERGENiHBG006672.
InParanoidiO08919.
KOiK06057.
OMAiPEQHLPP.
OrthoDBiEOG7MKW5J.
TreeFamiTF314159.

Miscellaneous databases

ChiTaRSiNumbl. mouse.
PROiO08919.
SOURCEiSearch...

Gene expression databases

BgeeiO08919.
CleanExiMM_NUMBL.
GenevisibleiO08919. MM.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR016698. Numb/numb-like.
IPR010449. Numb_domain.
IPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
[Graphical view]
PfamiPF06311. NumbF. 1 hit.
PF00640. PID. 1 hit.
[Graphical view]
PIRSFiPIRSF017607. Numb/numb-like. 1 hit.
SMARTiSM00462. PTB. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS01179. PID. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Differential expression of mammalian Numb, Numblike and Notch1 suggests distinct roles during mouse cortical neurogenesis."
    Zhong W., Jiang M.-M., Weinmaster G., Jan L.Y., Jan Y.N.
    Development 124:1887-1897(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Tissue: Embryo.
  2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain.
  4. "Progenitor cell maintenance requires numb and numblike during mouse neurogenesis."
    Petersen P.H., Zou K., Hwang J.K., Jan Y.N., Zhong W.
    Nature 419:929-934(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
  5. "Continuing role for mouse Numb and Numbl in maintaining progenitor cells during cortical neurogenesis."
    Petersen P.H., Zou K., Krauss S., Zhong W.
    Nat. Neurosci. 7:803-811(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
  6. "Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche."
    Kuo C.T., Mirzadeh Z., Soriano-Navarro M., Rasin M., Wang D., Shen J., Sestan N., Garcia-Verdugo J., Alvarez-Buylla A., Jan L.Y., Jan Y.N.
    Cell 127:1253-1264(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. "Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations."
    Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M.
    Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain cortex.
  8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.

Entry informationi

Entry nameiNUMBL_MOUSE
AccessioniPrimary (citable) accession number: O08919
Secondary accession number(s): Q4QQQ2, Q6NVG8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: July 27, 2011
Last modified: July 6, 2016
This is version 129 of the entry and version 3 of the sequence. [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
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.