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Protein

Numb-like protein

Gene

Numbl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionDevelopmental protein
Biological processNeurogenesis, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:894702 Numbl

Subcellular locationi

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)DescriptionActionsGraphical viewLength
ChainiPRO_00000580001 – 604Numb-like proteinAdd BLAST604

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei224PhosphoserineBy similarity1
Modified residuei228PhosphoserineBy similarity1
Modified residuei263PhosphoserineBy similarity1
Modified residuei279PhosphothreonineBy similarity1
Modified residuei411PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO08919
MaxQBiO08919
PaxDbiO08919
PeptideAtlasiO08919
PRIDEiO08919

PTM databases

iPTMnetiO08919
PhosphoSitePlusiO08919

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

BgeeiENSMUSG00000063160 Expressed in 212 organ(s), highest expression level in retina
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, 4 interactors
IntActiO08919, 4 interactors
STRINGi10090.ENSMUSP00000078245

Structurei

3D structure databases

ProteinModelPortaliO08919
SMRiO08919
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini74 – 225PIDPROSITE-ProRule annotationAdd BLAST152

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi422 – 441Gln-richAdd BLAST20

Domaini

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

Phylogenomic databases

eggNOGiKOG3537 Eukaryota
ENOG410XT15 LUCA
GeneTreeiENSGT00530000062937
HOGENOMiHOG000220819
HOVERGENiHBG006672
InParanoidiO08919
KOiK06057
OMAiCNFAVRY
OrthoDBiEOG091G0FJH
TreeFamiTF314159

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR016698 Numb/numb-like
IPR010449 Numb_domain
IPR011993 PH-like_dom_sf
IPR006020 PTB/PI_dom
PfamiView protein in Pfam
PF06311 NumbF, 1 hit
PF00640 PID, 1 hit
PIRSFiPIRSF017607 Numb/numb-like, 1 hit
SMARTiView protein in SMART
SM00462 PTB, 1 hit
PROSITEiView protein in PROSITE
PS01179 PID, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti28P → A in AAB58697 (PubMed:9169836).Curated1
Sequence conflicti244Missing in AAB58697 (PubMed:9169836).Curated1
Sequence conflicti589S → F in AAH68116 (PubMed:15489334).Curated1

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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201878, 4 interactors
IntActiO08919, 4 interactors
STRINGi10090.ENSMUSP00000078245

PTM databases

iPTMnetiO08919
PhosphoSitePlusiO08919

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
OMAiCNFAVRY
OrthoDBiEOG091G0FJH
TreeFamiTF314159

Miscellaneous databases

ChiTaRSiNumbl mouse
PROiPR:O08919
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000063160 Expressed in 212 organ(s), highest expression level in retina
CleanExiMM_NUMBL
GenevisibleiO08919 MM

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR016698 Numb/numb-like
IPR010449 Numb_domain
IPR011993 PH-like_dom_sf
IPR006020 PTB/PI_dom
PfamiView protein in Pfam
PF06311 NumbF, 1 hit
PF00640 PID, 1 hit
PIRSFiPIRSF017607 Numb/numb-like, 1 hit
SMARTiView protein in SMART
SM00462 PTB, 1 hit
PROSITEiView protein in PROSITE
PS01179 PID, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNUMBL_MOUSE
AccessioniPrimary (citable) accession number: O08919
Secondary accession number(s): Q4QQQ2, Q6NVG8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 143 of the entry and version 3 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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