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Q9Y6R0 (NUMBL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Numb-like protein
Alternative name(s):
Numb-related protein
Short name=Numb-R
Gene names
Name:NUMBL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length609 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.7

Subunit structure

Interacts (via PTB domain) with MAP3K7IP2 (via C-terminal). Interacts (via C-terminal) with TRAF6 (via TRAF domains). Associates with EPS15 and NOTCH1. Ref.5 Ref.7

Subcellular location

Cytoplasm By similarity. Note: Symmetrically distributed throughout the cytoplasm in non dividing neuroblasts of the CNS By similarity. Ref.5

Domain

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

Sequence similarities

Contains 1 PID domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RBFOX1Q9NWB12EBI-945925,EBI-945906

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 609609Numb-like protein
PRO_0000057999

Regions

Domain74 – 223150PID
Compositional bias427 – 44620Poly-Gln

Amino acid modifications

Modified residue2791Phosphothreonine Ref.6

Secondary structure

....................... 609
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Y6R0 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 69458D161B60F4B4

FASTA60964,891
        10         20         30         40         50         60 
MSRSAAASGG PRRPERHLPP APCGAPGPPE TCRTEPDGAG TMNKLRQSLR RRKPAYVPEA 

        70         80         90        100        110        120 
SRPHQWQADE DAVRKGTCSF PVRYLGHVEV EESRGMHVCE DAVKKLKAMG RKSVKSVLWV 

       130        140        150        160        170        180 
SADGLRVVDD KTKDLLVDQT IEKVSFCAPD RNLDKAFSYI CRDGTTRRWI CHCFLALKDS 

       190        200        210        220        230        240 
GERLSHAVGC AFAACLERKQ RREKECGVTA AFDASRTSFA REGSFRLSGG GRPAEREAPD 

       250        260        270        280        290        300 
KKKAEAAAAP TVAPGPAQPG HVSPTPATTS PGEKGEAGTP VAAGTTAAAI PRRHAPLEQL 

       310        320        330        340        350        360 
VRQGSFRGFP ALSQKNSPFK RQLSLRLNEL PSTLQRRTDF QVKGTVPEME PPGAGDSDSI 

       370        380        390        400        410        420 
NALCTQISSS FASAGAPAPG PPPATTGTSA WGEPSVPPAA AFQPGHKRTP SEAERWLEEV 

       430        440        450        460        470        480 
SQVAKAQQQQ QQQQQQQQQQ QQQQQQAASV APVPTMPPAL QPFPAPVGPF DAAPAQVAVF 

       490        500        510        520        530        540 
LPPPHMQPPF VPAYPGLGYP PMPRVPVVGI TPSQMVANAF CSAAQLQPQP ATLLGKAGAF 

       550        560        570        580        590        600 
PPPAIPSAPG SQARPRPNGA PWPPEPAPAP APELDPFEAQ WAALEGKATV EKPSNPFSGD 


LQKTFEIEL 

« Hide

References

« Hide 'large scale' references
[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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF015041 mRNA. Translation: AAD01549.1.
BC001794 mRNA. No translation available.
BT009807 mRNA. Translation: AAP88809.1.
RefSeqNP_004747.1. NM_004756.4.
UniGeneHs.326953.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3F0WX-ray2.70A60-204[»]
ProteinModelPortalQ9Y6R0.
SMRQ9Y6R0. Positions 60-202.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114677. 20 interactions.
IntActQ9Y6R0. 18 interactions.
MINTMINT-1497553.
STRING9606.ENSP00000252891.

PTM databases

PhosphoSiteQ9Y6R0.

Polymorphism databases

DMDM14194976.

Proteomic databases

PaxDbQ9Y6R0.
PRIDEQ9Y6R0.

Protocols and materials databases

DNASU9253.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252891; ENSP00000252891; ENSG00000105245.
ENST00000540131; ENSP00000442759; ENSG00000105245.
ENST00000598779; ENSP00000472400; ENSG00000105245.
GeneID9253.
KEGGhsa:9253.
UCSCuc002oon.3. human.

Organism-specific databases

CTD9253.
GeneCardsGC19M041171.
HGNCHGNC:8061. NUMBL.
HPAHPA058251.
HPA058380.
MIM604018. gene.
neXtProtNX_Q9Y6R0.
PharmGKBPA31846.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG331167.
HOGENOMHOG000220819.
HOVERGENHBG006672.
InParanoidQ9Y6R0.
KOK06057.
OMAPEQHLPP.
OrthoDBEOG7MKW5J.
PhylomeDBQ9Y6R0.
TreeFamTF314159.

Enzyme and pathway databases

SignaLinkQ9Y6R0.

Gene expression databases

ArrayExpressQ9Y6R0.
BgeeQ9Y6R0.
CleanExHS_NUMBL.
GenevestigatorQ9Y6R0.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR016698. Numb/numb-like.
IPR010449. Numb_domain.
IPR011993. PH_like_dom.
IPR006020. PTB/PI_dom.
[Graphical view]
PfamPF06311. NumbF. 1 hit.
PF00640. PID. 1 hit.
[Graphical view]
PIRSFPIRSF017607. Numb/numb-like. 1 hit.
SMARTSM00462. PTB. 1 hit.
[Graphical view]
PROSITEPS01179. PID. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNUMBL. human.
EvolutionaryTraceQ9Y6R0.
GeneWikiNUMBL.
GenomeRNAi9253.
NextBio34685.
PROQ9Y6R0.
SOURCESearch...

Entry information

Entry nameNUMBL_HUMAN
AccessionPrimary (citable) accession number: Q9Y6R0
Secondary accession number(s): Q7Z4J9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: November 1, 1999
Last modified: April 16, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM