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Q9Y6R0

- NUMBL_HUMAN

UniProt

Q9Y6R0 - NUMBL_HUMAN

Protein

Numb-like protein

Gene

NUMBL

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    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 - Molecular functioni

    1. protein binding Source: UniProtKB

    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

    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: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:8061. NUMBL.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA31846.

    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

    ArrayExpressiQ9Y6R0.
    BgeeiQ9Y6R0.
    CleanExiHS_NUMBL.
    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. 20 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 – 663
    Helixi67 – 748
    Beta strandi78 – 9114
    Helixi96 – 10712
    Beta strandi114 – 1207
    Beta strandi122 – 1298
    Turni130 – 1323
    Beta strandi135 – 1406
    Helixi141 – 1433
    Beta strandi144 – 1496
    Beta strandi156 – 1638
    Turni164 – 1674
    Beta strandi168 – 17912
    Helixi181 – 20121

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    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

    MSRSAAASGG PRRPERHLPP APCGAPGPPE TCRTEPDGAG TMNKLRQSLR    50
    RRKPAYVPEA SRPHQWQADE DAVRKGTCSF PVRYLGHVEV EESRGMHVCE 100
    DAVKKLKAMG RKSVKSVLWV SADGLRVVDD KTKDLLVDQT IEKVSFCAPD 150
    RNLDKAFSYI CRDGTTRRWI CHCFLALKDS GERLSHAVGC AFAACLERKQ 200
    RREKECGVTA AFDASRTSFA REGSFRLSGG GRPAEREAPD KKKAEAAAAP 250
    TVAPGPAQPG HVSPTPATTS PGEKGEAGTP VAAGTTAAAI PRRHAPLEQL 300
    VRQGSFRGFP ALSQKNSPFK RQLSLRLNEL PSTLQRRTDF QVKGTVPEME 350
    PPGAGDSDSI NALCTQISSS FASAGAPAPG PPPATTGTSA WGEPSVPPAA 400
    AFQPGHKRTP SEAERWLEEV SQVAKAQQQQ QQQQQQQQQQ QQQQQQAASV 450
    APVPTMPPAL QPFPAPVGPF DAAPAQVAVF LPPPHMQPPF VPAYPGLGYP 500
    PMPRVPVVGI TPSQMVANAF CSAAQLQPQP ATLLGKAGAF PPPAIPSAPG 550
    SQARPRPNGA PWPPEPAPAP APELDPFEAQ WAALEGKATV EKPSNPFSGD 600
    LQKTFEIEL 609
    Length:609
    Mass (Da):64,891
    Last modified:November 1, 1999 - v1
    Checksum:i69458D161B60F4B4
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    ENST00000540131; ENSP00000442759; ENSG00000105245.
    ENST00000598779; ENSP00000472400; ENSG00000105245.
    GeneIDi9253.
    KEGGihsa:9253.
    UCSCiuc002oon.3. human.

    Polymorphism databases

    DMDMi14194976.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF015041 mRNA. Translation: AAD01549.1 .
    BC001794 mRNA. No translation available.
    BT009807 mRNA. Translation: AAP88809.1 .
    CCDSi CCDS12561.1.
    RefSeqi NP_001276908.1. NM_001289979.1.
    NP_001276909.1. NM_001289980.1.
    NP_004747.1. NM_004756.4.
    UniGenei Hs.326953.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3F0W X-ray 2.70 A 60-204 [» ]
    ProteinModelPortali Q9Y6R0.
    SMRi Q9Y6R0. Positions 60-202.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114677. 20 interactions.
    IntActi Q9Y6R0. 18 interactions.
    MINTi MINT-1497553.
    STRINGi 9606.ENSP00000252891.

    PTM databases

    PhosphoSitei Q9Y6R0.

    Polymorphism databases

    DMDMi 14194976.

    Proteomic databases

    MaxQBi Q9Y6R0.
    PaxDbi Q9Y6R0.
    PRIDEi Q9Y6R0.

    Protocols and materials databases

    DNASUi 9253.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000252891 ; ENSP00000252891 ; ENSG00000105245 .
    ENST00000540131 ; ENSP00000442759 ; ENSG00000105245 .
    ENST00000598779 ; ENSP00000472400 ; ENSG00000105245 .
    GeneIDi 9253.
    KEGGi hsa:9253.
    UCSCi uc002oon.3. human.

    Organism-specific databases

    CTDi 9253.
    GeneCardsi GC19M041171.
    HGNCi HGNC:8061. NUMBL.
    HPAi HPA058251.
    HPA058380.
    MIMi 604018. gene.
    neXtProti NX_Q9Y6R0.
    PharmGKBi PA31846.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG331167.
    HOGENOMi HOG000220819.
    HOVERGENi HBG006672.
    InParanoidi Q9Y6R0.
    KOi K06057.
    OMAi PEQHLPP.
    OrthoDBi EOG7MKW5J.
    PhylomeDBi Q9Y6R0.
    TreeFami TF314159.

    Enzyme and pathway databases

    SignaLinki Q9Y6R0.

    Miscellaneous databases

    ChiTaRSi NUMBL. human.
    EvolutionaryTracei Q9Y6R0.
    GeneWikii NUMBL.
    GenomeRNAii 9253.
    NextBioi 34685.
    PROi Q9Y6R0.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y6R0.
    Bgeei Q9Y6R0.
    CleanExi HS_NUMBL.
    Genevestigatori Q9Y6R0.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    InterProi IPR016698. Numb/numb-like.
    IPR010449. Numb_domain.
    IPR011993. PH_like_dom.
    IPR006020. PTB/PI_dom.
    [Graphical view ]
    Pfami PF06311. NumbF. 1 hit.
    PF00640. PID. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF017607. Numb/numb-like. 1 hit.
    SMARTi SM00462. PTB. 1 hit.
    [Graphical view ]
    PROSITEi PS01179. PID. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 123 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