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Protein

Numb-like protein

Gene

NUMBL

Organism
Homo sapiens (Human)
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.2 Publications

GO - Biological processi

  1. adherens junction organization Source: Ensembl
  2. axonogenesis Source: Ensembl
  3. cytokine-mediated signaling pathway Source: UniProtKB
  4. lateral ventricle development Source: UniProtKB
  5. nervous system development Source: ProtInc
  6. neuroblast division in subventricular zone Source: UniProtKB
  7. positive regulation of dendrite morphogenesis Source: Ensembl
  8. positive regulation of neurogenesis Source: UniProtKB
  9. protein metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Neurogenesis, Ubl conjugation pathway

Enzyme and pathway databases

SignaLinkiQ9Y6R0.

Names & Taxonomyi

Protein namesi
Recommended name:
Numb-like protein
Alternative name(s):
Numb-related protein
Short name:
Numb-R
Gene namesi
Name:NUMBL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:8061. NUMBL.

Subcellular locationi

  1. Cytoplasm By similarity

  2. Note: Symmetrically distributed throughout the cytoplasm in non dividing neuroblasts of the CNS.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31846.

Polymorphism and mutation databases

BioMutaiNUMBL.
DMDMi14194976.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 609609Numb-like proteinPRO_0000057999Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei279 – 2791Phosphothreonine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Y6R0.
PaxDbiQ9Y6R0.
PRIDEiQ9Y6R0.

PTM databases

PhosphoSiteiQ9Y6R0.

Expressioni

Gene expression databases

BgeeiQ9Y6R0.
CleanExiHS_NUMBL.
ExpressionAtlasiQ9Y6R0. baseline and differential.
GenevestigatoriQ9Y6R0.

Organism-specific databases

HPAiHPA058251.
HPA058380.

Interactioni

Subunit structurei

Interacts (via PTB domain) with MAP3K7IP2 (via C-terminal). Interacts (via C-terminal) with TRAF6 (via TRAF domains). Associates with EPS15 and NOTCH1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RBFOX1Q9NWB12EBI-945925,EBI-945906

Protein-protein interaction databases

BioGridi114677. 24 interactions.
IntActiQ9Y6R0. 18 interactions.
MINTiMINT-1497553.
STRINGi9606.ENSP00000252891.

Structurei

Secondary structure

1
609
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni64 – 663Combined sources
Helixi67 – 748Combined sources
Beta strandi78 – 9114Combined sources
Helixi96 – 10712Combined sources
Beta strandi114 – 1207Combined sources
Beta strandi122 – 1298Combined sources
Turni130 – 1323Combined sources
Beta strandi135 – 1406Combined sources
Helixi141 – 1433Combined sources
Beta strandi144 – 1496Combined sources
Beta strandi156 – 1638Combined sources
Turni164 – 1674Combined sources
Beta strandi168 – 17912Combined sources
Helixi181 – 20121Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3F0WX-ray2.70A60-204[»]
ProteinModelPortaliQ9Y6R0.
SMRiQ9Y6R0. Positions 60-202.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y6R0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini74 – 223150PIDPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi427 – 44620Poly-GlnAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 PID domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG331167.
GeneTreeiENSGT00530000062937.
HOGENOMiHOG000220819.
HOVERGENiHBG006672.
InParanoidiQ9Y6R0.
KOiK06057.
OMAiPEQHLPP.
OrthoDBiEOG7MKW5J.
PhylomeDBiQ9Y6R0.
TreeFamiTF314159.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR016698. Numb/numb-like.
IPR010449. Numb_domain.
IPR011993. PH_like_dom.
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]
PROSITEiPS01179. PID. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Y6R0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRSAAASGG PRRPERHLPP APCGAPGPPE TCRTEPDGAG 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 GRPAEREAPD KKKAEAAAAP
260 270 280 290 300
TVAPGPAQPG HVSPTPATTS PGEKGEAGTP VAAGTTAAAI PRRHAPLEQL
310 320 330 340 350
VRQGSFRGFP ALSQKNSPFK RQLSLRLNEL PSTLQRRTDF QVKGTVPEME
360 370 380 390 400
PPGAGDSDSI NALCTQISSS FASAGAPAPG PPPATTGTSA WGEPSVPPAA
410 420 430 440 450
AFQPGHKRTP SEAERWLEEV SQVAKAQQQQ QQQQQQQQQQ QQQQQQAASV
460 470 480 490 500
APVPTMPPAL QPFPAPVGPF DAAPAQVAVF LPPPHMQPPF VPAYPGLGYP
510 520 530 540 550
PMPRVPVVGI TPSQMVANAF CSAAQLQPQP ATLLGKAGAF PPPAIPSAPG
560 570 580 590 600
SQARPRPNGA PWPPEPAPAP APELDPFEAQ WAALEGKATV EKPSNPFSGD

LQKTFEIEL
Length:609
Mass (Da):64,891
Last modified:November 1, 1999 - v1
Checksum:i69458D161B60F4B4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF015041 mRNA. Translation: AAD01549.1.
BC001794 mRNA. No translation available.
BT009807 mRNA. Translation: AAP88809.1.
CCDSiCCDS12561.1.
RefSeqiNP_001276908.1. NM_001289979.1.
NP_001276909.1. NM_001289980.1.
NP_004747.1. NM_004756.4.
UniGeneiHs.326953.

Genome annotation databases

EnsembliENST00000252891; ENSP00000252891; ENSG00000105245.
GeneIDi9253.
KEGGihsa:9253.
UCSCiuc002oon.3. human.

Polymorphism and mutation databases

BioMutaiNUMBL.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF015041 mRNA. Translation: AAD01549.1.
BC001794 mRNA. No translation available.
BT009807 mRNA. Translation: AAP88809.1.
CCDSiCCDS12561.1.
RefSeqiNP_001276908.1. NM_001289979.1.
NP_001276909.1. NM_001289980.1.
NP_004747.1. NM_004756.4.
UniGeneiHs.326953.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3F0WX-ray2.70A60-204[»]
ProteinModelPortaliQ9Y6R0.
SMRiQ9Y6R0. Positions 60-202.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114677. 24 interactions.
IntActiQ9Y6R0. 18 interactions.
MINTiMINT-1497553.
STRINGi9606.ENSP00000252891.

PTM databases

PhosphoSiteiQ9Y6R0.

Polymorphism and mutation databases

BioMutaiNUMBL.
DMDMi14194976.

Proteomic databases

MaxQBiQ9Y6R0.
PaxDbiQ9Y6R0.
PRIDEiQ9Y6R0.

Protocols and materials databases

DNASUi9253.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252891; ENSP00000252891; ENSG00000105245.
GeneIDi9253.
KEGGihsa:9253.
UCSCiuc002oon.3. human.

Organism-specific databases

CTDi9253.
GeneCardsiGC19M041171.
HGNCiHGNC:8061. NUMBL.
HPAiHPA058251.
HPA058380.
MIMi604018. gene.
neXtProtiNX_Q9Y6R0.
PharmGKBiPA31846.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG331167.
GeneTreeiENSGT00530000062937.
HOGENOMiHOG000220819.
HOVERGENiHBG006672.
InParanoidiQ9Y6R0.
KOiK06057.
OMAiPEQHLPP.
OrthoDBiEOG7MKW5J.
PhylomeDBiQ9Y6R0.
TreeFamiTF314159.

Enzyme and pathway databases

SignaLinkiQ9Y6R0.

Miscellaneous databases

ChiTaRSiNUMBL. human.
EvolutionaryTraceiQ9Y6R0.
GeneWikiiNUMBL.
GenomeRNAii9253.
NextBioi34685.
PROiQ9Y6R0.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y6R0.
CleanExiHS_NUMBL.
ExpressionAtlasiQ9Y6R0. baseline and differential.
GenevestigatoriQ9Y6R0.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR016698. Numb/numb-like.
IPR010449. Numb_domain.
IPR011993. PH_like_dom.
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]
PROSITEiPS01179. PID. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module."
    Salcini A.E., Confalonieri S., Doria M., Santolini E., Tassi E., Minenkova O., Cesareni G., Pelicci P.G., Di Fiore P.P.
    Genes Dev. 11:2239-2249(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "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] OF 9-609.
    Tissue: Eye.
  3. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-609.
  4. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
    Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  5. "NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced NF-kappaB activation."
    Ma Q., Zhou L., Shi H., Huo K.
    Cell. Signal. 20:1044-1051(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MAP3K7IP2, SUBCELLULAR LOCATION.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-279, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. "NUMBL interacts with TRAF6 and promotes the degradation of TRAF6."
    Zhou L., Ma Q., Shi H., Huo K.
    Biochem. Biophys. Res. Commun. 392:409-414(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TRAF6.
  8. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  9. "Human numb-like protein, phosphotyrosine interaction domain."
    Structural genomics consortium (SGC)
    Submitted (FEB-2009) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 60-204.

Entry informationi

Entry nameiNUMBL_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6R0
Secondary accession number(s): Q7Z4J9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: November 1, 1999
Last modified: April 29, 2015
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.