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Protein

Protein numb homolog

Gene

Numb

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 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

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processNeurogenesis

Enzyme and pathway databases

ReactomeiR-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:107423 Numb

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

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 Expressed in 302 organ(s), highest expression level in urothelium
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201877, 28 interactors
CORUMiQ9QZS3
IntActiQ9QZS3, 21 interactors
MINTiQ9QZS3
STRINGi10090.ENSMUSP00000119303

Structurei

Secondary structure

1653
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9QZS3
SMRiQ9QZS3
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9QZS3

Family & Domainsi

Domains and Repeats

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

Phylogenomic databases

eggNOGiKOG3537 Eukaryota
ENOG410XT15 LUCA
GeneTreeiENSGT00530000062937
HOGENOMiHOG000220819
HOVERGENiHBG006672
InParanoidiQ9QZS3
KOiK06057
OMAiHSGTEWG
OrthoDBiEOG091G0FJH
PhylomeDBiQ9QZS3
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

Sequences (4+)i

Sequence statusi: Complete.

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

This entry has 4 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q05BE7Q05BE7_MOUSE
Numb protein
Numb
322Annotation score:
D3Z1E8D3Z1E8_MOUSE
Protein numb homolog
Numb
163Annotation score:
D3Z549D3Z549_MOUSE
Protein numb homolog
Numb
113Annotation score:
D3Z7I6D3Z7I6_MOUSE
Protein numb homolog
Numb
148Annotation score:
F8WJ71F8WJ71_MOUSE
Protein numb homolog
Numb
76Annotation score:
D3Z7J1D3Z7J1_MOUSE
Protein numb homolog
Numb
65Annotation score:
A0A1Y7VJJ7A0A1Y7VJJ7_MOUSE
Protein numb homolog
Numb
36Annotation score:

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

Similar proteinsi

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[»]
5YQGX-ray2.10E/F271-301[»]
ProteinModelPortaliQ9QZS3
SMRiQ9QZS3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201877, 28 interactors
CORUMiQ9QZS3
IntActiQ9QZS3, 21 interactors
MINTiQ9QZS3
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
OMAiHSGTEWG
OrthoDBiEOG091G0FJH
PhylomeDBiQ9QZS3
TreeFamiTF314159

Enzyme and pathway databases

ReactomeiR-MMU-437239 Recycling pathway of L1
R-MMU-5610780 Degradation of GLI1 by the proteasome
R-MMU-5632684 Hedgehog 'on' state

Miscellaneous databases

EvolutionaryTraceiQ9QZS3
PROiPR:Q9QZS3
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021224 Expressed in 302 organ(s), highest expression level in urothelium
CleanExiMM_NUMB
ExpressionAtlasiQ9QZS3 baseline and differential
GenevisibleiQ9QZS3 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 nameiNUMB_MOUSE
AccessioniPrimary (citable) accession number: Q9QZS3
Secondary accession number(s): P70422
, Q8CIB1, Q9DC57, Q9QZR1, Q9QZS4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 168 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

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
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Main funding by: National Institutes of Health

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