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Protein

Protein numb homolog

Gene

Numb

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 neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. May also mediate local repair of brain ventricular wall damage.4 Publications

GO - Molecular functioni

  • alpha-catenin binding Source: MGI
  • beta-catenin binding Source: MGI
  • cadherin binding Source: MGI
  • cadherin binding involved in cell-cell adhesion Source: MGI

GO - Biological processi

  • adherens junction organization Source: MGI
  • axonogenesis Source: MGI
  • forebrain development Source: MGI
  • lateral ventricle development Source: UniProtKB
  • lung epithelial cell differentiation Source: MGI
  • negative regulation of Notch signaling pathway Source: MGI
  • negative regulation of protein localization to plasma membrane Source: MGI
  • nervous system development Source: MGI
  • neuroblast division in subventricular zone Source: UniProtKB
  • neuroblast proliferation Source: MGI
  • Notch signaling pathway Source: Reactome
  • positive regulation of cell migration Source: MGI
  • positive regulation of neurogenesis Source: UniProtKB
  • positive regulation of polarized epithelial cell differentiation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Neurogenesis

Enzyme and pathway databases

ReactomeiR-MMU-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-MMU-437239. Recycling pathway of L1.
R-MMU-5610780. Degradation of GLI1 by the proteasome.
R-MMU-5632684. Hedgehog 'on' state.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein numb homolog
Short name:
m-Nb
Short name:
m-Numb
Gene namesi
Name:Numb
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:107423. Numb.

Subcellular locationi

GO - Cellular componenti

  • apical part of cell Source: MGI
  • basolateral plasma membrane Source: MGI
  • cell-cell adherens junction Source: MGI
  • clathrin-coated vesicle Source: MGI
  • cytoplasm Source: MGI
  • cytoplasmic, membrane-bounded vesicle Source: BHF-UCL
  • early endosome Source: MGI
  • extrinsic component of plasma membrane Source: MGI
  • focal adhesion Source: MGI
  • nucleus Source: MGI
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

Mutant animals exhibit severe defects in cranial neuronal tube closure and die around 11.5 dpc, but neurogenesis abnormalities are limited. 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 mutants, with expression abrogated in neural progenitor cells from 8.5 dpc are viable, fertile and exhibit no obvious phenotypes. 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 neuronal 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 a 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.4 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000580021 – 653Protein numb homologAdd BLAST653

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei194PhosphoserineBy similarity1
Modified residuei243PhosphothreonineCombined sources1
Modified residuei244PhosphoserineCombined sources1
Modified residuei276Phosphoserine; by CaMK1By similarity1
Modified residuei295Phosphoserine; by CaMK1By similarity1
Modified residuei427PhosphoserineBy similarity1
Modified residuei438PhosphothreonineBy similarity1
Modified residuei440PhosphoserineCombined sources1
Modified residuei636PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on Ser-276 and Ser-295 by CaMK1.By similarity
Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation (By similarity) Isoform 1 and isoform 2 are ubiquitinated by LNX leading to their subsequent proteasomal degradation.By similarity1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9QZS3.
PeptideAtlasiQ9QZS3.
PRIDEiQ9QZS3.

PTM databases

iPTMnetiQ9QZS3.
PhosphoSitePlusiQ9QZS3.

Expressioni

Tissue specificityi

Expressed in subventricular zone (SVZ) neuroprogenitors and ependymal cells.1 Publication

Developmental stagei

Expressed in neural progenitors 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

BgeeiENSMUSG00000021224.
CleanExiMM_NUMB.
ExpressionAtlasiQ9QZS3. baseline and differential.
GenevisibleiQ9QZS3. MM.

Interactioni

Subunit structurei

May interact with DUOXA1 (By similarity). Interacts with TFAP2B (By similarity). Interacts with CDH1, EPS15, LNX and NOTCH1. Interacts with RALBP1 in a complex also containing EPN1 and TFAP2A during interphase and mitosis.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EPS15P425663EBI-3896014,EBI-396684From a different organism.
GLI1P081514EBI-3896014,EBI-308084From a different organism.
ITCHQ96J022EBI-3896014,EBI-1564678From a different organism.
REPS1Q96D713EBI-9547433,EBI-1171195From a different organism.

GO - Molecular functioni

  • alpha-catenin binding Source: MGI
  • beta-catenin binding Source: MGI
  • cadherin binding Source: MGI
  • cadherin binding involved in cell-cell adhesion Source: MGI

Protein-protein interaction databases

BioGridi201877. 28 interactors.
IntActiQ9QZS3. 21 interactors.
MINTiMINT-237633.
STRINGi10090.ENSMUSP00000119303.

Structurei

Secondary structure

1653
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi26 – 31Combined sources6
Turni32 – 35Combined sources4
Beta strandi38 – 48Combined sources11
Beta strandi50 – 52Combined sources3
Helixi55 – 68Combined sources14
Beta strandi84 – 91Combined sources8
Beta strandi94 – 98Combined sources5
Turni100 – 102Combined sources3
Beta strandi105 – 107Combined sources3
Turni111 – 113Combined sources3
Beta strandi116 – 118Combined sources3
Beta strandi121 – 132Combined sources12
Beta strandi134 – 149Combined sources16
Helixi151 – 169Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WJ1NMR-A19-172[»]
ProteinModelPortaliQ9QZS3.
SMRiQ9QZS3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9QZS3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 193PIDPROSITE-ProRule annotationAdd BLAST161

Sequence similaritiesi

Contains 1 PID domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3537. Eukaryota.
ENOG410XT15. LUCA.
GeneTreeiENSGT00530000062937.
HOGENOMiHOG000220819.
HOVERGENiHBG006672.
InParanoidiQ9QZS3.
KOiK06057.
OMAiRKTDFPM.
OrthoDBiEOG091G0FJH.
PhylomeDBiQ9QZS3.
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]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9QZS3-1) [UniParc]FASTAAdd to basket
Also known as: p72, 72 kDa

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNKLRQSFRR KKDVYVPEAS RPHQWQTDEE GVRTGKCSFP VKYLGHVEVD
60 70 80 90 100
ESRGMHICED AVKRLKAERK FFKGFFGKTG KKAVKAVLWV SADGLRVVDE
110 120 130 140 150
KTKDLIVDQT IEKVSFCAPD RNFDRAFSYI CRDGTTRRWI CHCFMAVKDT
160 170 180 190 200
GERLSHAVGC AFAACLERKQ KREKECGVTA TFDASRTTFT REGSFRVTTA
210 220 230 240 250
TEQAEREEIM KQLQDAKKAE TDKTVVGPSV APGNTAPSPS SPTSPTPDGT
260 270 280 290 300
ASSEMNNPHA IPRRHAPIEQ LARQGSFRGF PALSQKMSPF KRQLSLRINE
310 320 330 340 350
LPSTMQRKTD FPIKNTVPEV EGEAESISSL CSQITSAFST PSEDPFSSAP
360 370 380 390 400
MTKPVTLVAP QSPVLQANGT DSASHVLTAK PANTALAHVA MPVRETNPWA
410 420 430 440 450
HVPDAANKEI AAIHPGTEWG QSSGAASPGL FQAGHRRTPS EADRWLEEVS
460 470 480 490 500
KSVRAQQPQV SAAPLQPVLQ PPPPAAIAPP APPFQGHAFL TSQPVPVGVV
510 520 530 540 550
PPLQPAFVPT QSYPVANGMP YPASNVPVVG ITPSQMVANV FGTAGHPQTT
560 570 580 590 600
HPHQSPSLAK QQTFPQYETS SATTSPFFKP PAQHLNGSAA FNGVDNGGLA
610 620 630 640 650
SGNRHAEVPP GTCPVDPFEA QWAALESKSK QRTNPSPTNP FSSDLQKTFE

IEL
Length:653
Mass (Da):70,813
Last modified:May 1, 2000 - v1
Checksum:i6A2B69AA54B9A928
GO
Isoform 2 (identifier: Q9QZS3-2) [UniParc]FASTAAdd to basket
Also known as: p66, 66 kDa

The sequence of this isoform differs from the canonical sequence as follows:
     367-415: Missing.

Show »
Length:604
Mass (Da):65,766
Checksum:i709C36BE4DEF6AE0
GO
Isoform 3 (identifier: Q9QZS3-3) [UniParc]FASTAAdd to basket
Also known as: p71, 71 kDa

The sequence of this isoform differs from the canonical sequence as follows:
     68-78: Missing.

Show »
Length:642
Mass (Da):69,440
Checksum:i2419437F0400E691
GO
Isoform 4 (identifier: Q9QZS3-4) [UniParc]FASTAAdd to basket
Also known as: p65, 65 kDa

The sequence of this isoform differs from the canonical sequence as follows:
     68-78: Missing.
     367-415: Missing.

Show »
Length:593
Mass (Da):64,394
Checksum:i6DFF734800C4D49C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti225V → A in AAH33459 (PubMed:15489334).Curated1
Sequence conflicti362S → C in BAB23367 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00435068 – 78Missing in isoform 3 and isoform 4. 4 PublicationsAdd BLAST11
Alternative sequenceiVSP_004351367 – 415Missing in isoform 2 and isoform 4. 4 PublicationsAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169191 mRNA. Translation: AAD47834.1.
AF169192 mRNA. Translation: AAD47835.1.
AF170709 mRNA. Translation: AAD47836.1.
AK004553 mRNA. Translation: BAB23367.1.
BC033459 mRNA. Translation: AAH33459.1.
U70674 mRNA. Translation: AAB09586.1.
CCDSiCCDS26032.1. [Q9QZS3-2]
CCDS49108.1. [Q9QZS3-1]
CCDS70400.1. [Q9QZS3-4]
CCDS70401.1. [Q9QZS3-3]
RefSeqiNP_001129547.1. NM_001136075.2. [Q9QZS3-1]
NP_001258984.1. NM_001272055.1. [Q9QZS3-3]
NP_001258985.1. NM_001272056.1. [Q9QZS3-4]
NP_035079.1. NM_010949.2. [Q9QZS3-2]
XP_006515639.1. XM_006515576.1. [Q9QZS3-1]
XP_006515640.1. XM_006515577.2. [Q9QZS3-1]
XP_006515641.1. XM_006515578.1. [Q9QZS3-3]
XP_011242314.1. XM_011244012.2. [Q9QZS3-1]
UniGeneiMm.4390.

Genome annotation databases

EnsembliENSMUST00000021647; ENSMUSP00000021647; ENSMUSG00000021224. [Q9QZS3-2]
ENSMUST00000117217; ENSMUSP00000113591; ENSMUSG00000021224. [Q9QZS3-4]
ENSMUST00000129335; ENSMUSP00000119303; ENSMUSG00000021224. [Q9QZS3-1]
ENSMUST00000154043; ENSMUSP00000117899; ENSMUSG00000021224. [Q9QZS3-3]
GeneIDi18222.
KEGGimmu:18222.
UCSCiuc007odu.2. mouse. [Q9QZS3-2]
uc007odv.2. mouse. [Q9QZS3-1]
uc007odw.2. mouse. [Q9QZS3-3]
uc007ody.2. mouse. [Q9QZS3-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169191 mRNA. Translation: AAD47834.1.
AF169192 mRNA. Translation: AAD47835.1.
AF170709 mRNA. Translation: AAD47836.1.
AK004553 mRNA. Translation: BAB23367.1.
BC033459 mRNA. Translation: AAH33459.1.
U70674 mRNA. Translation: AAB09586.1.
CCDSiCCDS26032.1. [Q9QZS3-2]
CCDS49108.1. [Q9QZS3-1]
CCDS70400.1. [Q9QZS3-4]
CCDS70401.1. [Q9QZS3-3]
RefSeqiNP_001129547.1. NM_001136075.2. [Q9QZS3-1]
NP_001258984.1. NM_001272055.1. [Q9QZS3-3]
NP_001258985.1. NM_001272056.1. [Q9QZS3-4]
NP_035079.1. NM_010949.2. [Q9QZS3-2]
XP_006515639.1. XM_006515576.1. [Q9QZS3-1]
XP_006515640.1. XM_006515577.2. [Q9QZS3-1]
XP_006515641.1. XM_006515578.1. [Q9QZS3-3]
XP_011242314.1. XM_011244012.2. [Q9QZS3-1]
UniGeneiMm.4390.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WJ1NMR-A19-172[»]
ProteinModelPortaliQ9QZS3.
SMRiQ9QZS3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201877. 28 interactors.
IntActiQ9QZS3. 21 interactors.
MINTiMINT-237633.
STRINGi10090.ENSMUSP00000119303.

PTM databases

iPTMnetiQ9QZS3.
PhosphoSitePlusiQ9QZS3.

Proteomic databases

PaxDbiQ9QZS3.
PeptideAtlasiQ9QZS3.
PRIDEiQ9QZS3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021647; ENSMUSP00000021647; ENSMUSG00000021224. [Q9QZS3-2]
ENSMUST00000117217; ENSMUSP00000113591; ENSMUSG00000021224. [Q9QZS3-4]
ENSMUST00000129335; ENSMUSP00000119303; ENSMUSG00000021224. [Q9QZS3-1]
ENSMUST00000154043; ENSMUSP00000117899; ENSMUSG00000021224. [Q9QZS3-3]
GeneIDi18222.
KEGGimmu:18222.
UCSCiuc007odu.2. mouse. [Q9QZS3-2]
uc007odv.2. mouse. [Q9QZS3-1]
uc007odw.2. mouse. [Q9QZS3-3]
uc007ody.2. mouse. [Q9QZS3-4]

Organism-specific databases

CTDi8650.
MGIiMGI:107423. Numb.

Phylogenomic databases

eggNOGiKOG3537. Eukaryota.
ENOG410XT15. LUCA.
GeneTreeiENSGT00530000062937.
HOGENOMiHOG000220819.
HOVERGENiHBG006672.
InParanoidiQ9QZS3.
KOiK06057.
OMAiRKTDFPM.
OrthoDBiEOG091G0FJH.
PhylomeDBiQ9QZS3.
TreeFamiTF314159.

Enzyme and pathway databases

ReactomeiR-MMU-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-MMU-437239. Recycling pathway of L1.
R-MMU-5610780. Degradation of GLI1 by the proteasome.
R-MMU-5632684. Hedgehog 'on' state.

Miscellaneous databases

EvolutionaryTraceiQ9QZS3.
PROiQ9QZS3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021224.
CleanExiMM_NUMB.
ExpressionAtlasiQ9QZS3. baseline and differential.
GenevisibleiQ9QZS3. 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...

Entry informationi

Entry nameiNUMB_MOUSE
AccessioniPrimary (citable) accession number: Q9QZS3
Secondary accession number(s): P70422
, Q8CIB1, Q9DC57, Q9QZR1, Q9QZS4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.