NUMBL_HUMAN
ID NUMBL_HUMAN Reviewed; 609 AA.
AC Q9Y6R0; Q7Z4J9;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Numb-like protein;
DE AltName: Full=Numb-related protein;
DE Short=Numb-R;
GN Name=NUMBL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9303539; DOI=10.1101/gad.11.17.2239;
RA Salcini A.E., Confalonieri S., Doria M., Santolini E., Tassi E.,
RA Minenkova O., Cesareni G., Pelicci P.G., Di Fiore P.P.;
RT "Binding specificity and in vivo targets of the EH domain, a novel protein-
RT protein interaction module.";
RL Genes Dev. 11:2239-2249(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-609.
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-609.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [5]
RP FUNCTION, INTERACTION WITH MAP3K7IP2, AND SUBCELLULAR LOCATION.
RX PubMed=18299187; DOI=10.1016/j.cellsig.2008.01.015;
RA Ma Q., Zhou L., Shi H., Huo K.;
RT "NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced NF-
RT kappaB activation.";
RL Cell. Signal. 20:1044-1051(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-279, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP FUNCTION, AND INTERACTION WITH TRAF6.
RX PubMed=20079715; DOI=10.1016/j.bbrc.2010.01.037;
RA Zhou L., Ma Q., Shi H., Huo K.;
RT "NUMBL interacts with TRAF6 and promotes the degradation of TRAF6.";
RL Biochem. Biophys. Res. Commun. 392:409-414(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-224; SER-228 AND SER-263, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 60-204.
RG Structural genomics consortium (SGC);
RT "Human numb-like protein, phosphotyrosine interaction domain.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Plays a role in the process of neurogenesis. Required
CC throughout embryonic neurogenesis to maintain neural progenitor cells,
CC also called radial glial cells (RGCs), by allowing their daughter cells
CC to choose progenitor over neuronal cell fate. Not required for the
CC proliferation of neural progenitor cells before the onset of embryonic
CC neurogenesis. Also required postnatally in the subventricular zone
CC (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal
CC wall integrity. Negative regulator of NF-kappa-B signaling pathway. The
CC inhibition of NF-kappa-B activation is mediated at least in part, by
CC preventing MAP3K7IP2 to interact with polyubiquitin chains of TRAF6 and
CC RIPK1 and by stimulating the 'Lys-48'-linked polyubiquitination and
CC degradation of TRAF6 in cortical neurons. {ECO:0000269|PubMed:18299187,
CC ECO:0000269|PubMed:20079715}.
CC -!- SUBUNIT: Interacts (via PTB domain) with MAP3K7IP2 (via C-terminal).
CC Interacts (via C-terminal) with TRAF6 (via TRAF domains). Associates
CC with EPS15 and NOTCH1. {ECO:0000269|PubMed:18299187,
CC ECO:0000269|PubMed:20079715}.
CC -!- INTERACTION:
CC Q9Y6R0; Q00535: CDK5; NbExp=3; IntAct=EBI-945925, EBI-1041567;
CC Q9Y6R0; O94985-2: CLSTN1; NbExp=3; IntAct=EBI-945925, EBI-16041593;
CC Q9Y6R0; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-945925, EBI-9090282;
CC Q9Y6R0; Q9NWB1: RBFOX1; NbExp=2; IntAct=EBI-945925, EBI-945906;
CC Q9Y6R0; Q6PJ21: SPSB3; NbExp=5; IntAct=EBI-945925, EBI-3937206;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Note=Symmetrically
CC distributed throughout the cytoplasm in non dividing neuroblasts of the
CC CNS. {ECO:0000250}.
CC -!- DOMAIN: The PTB domain is necessary for the inhibition of MAP3K7IP2-
CC mediated activation of NF-kappa-B.
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DR EMBL; AF015041; AAD01549.1; -; mRNA.
DR EMBL; BC001794; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BT009807; AAP88809.1; -; mRNA.
DR CCDS; CCDS12561.1; -.
DR RefSeq; NP_001276908.1; NM_001289979.1.
DR RefSeq; NP_001276909.1; NM_001289980.2.
DR RefSeq; NP_004747.1; NM_004756.4.
DR PDB; 3F0W; X-ray; 2.70 A; A=60-204.
DR PDBsum; 3F0W; -.
DR AlphaFoldDB; Q9Y6R0; -.
DR SMR; Q9Y6R0; -.
DR BioGRID; 114677; 95.
DR ELM; Q9Y6R0; -.
DR IntAct; Q9Y6R0; 40.
DR MINT; Q9Y6R0; -.
DR STRING; 9606.ENSP00000252891; -.
DR GlyGen; Q9Y6R0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y6R0; -.
DR MetOSite; Q9Y6R0; -.
DR PhosphoSitePlus; Q9Y6R0; -.
DR BioMuta; NUMBL; -.
DR DMDM; 14194976; -.
DR EPD; Q9Y6R0; -.
DR jPOST; Q9Y6R0; -.
DR MassIVE; Q9Y6R0; -.
DR MaxQB; Q9Y6R0; -.
DR PaxDb; Q9Y6R0; -.
DR PeptideAtlas; Q9Y6R0; -.
DR PRIDE; Q9Y6R0; -.
DR ProteomicsDB; 86771; -.
DR Antibodypedia; 30612; 272 antibodies from 32 providers.
DR DNASU; 9253; -.
DR Ensembl; ENST00000252891.8; ENSP00000252891.3; ENSG00000105245.9.
DR GeneID; 9253; -.
DR KEGG; hsa:9253; -.
DR MANE-Select; ENST00000252891.8; ENSP00000252891.3; NM_004756.5; NP_004747.1.
DR UCSC; uc002oon.5; human.
DR CTD; 9253; -.
DR DisGeNET; 9253; -.
DR GeneCards; NUMBL; -.
DR HGNC; HGNC:8061; NUMBL.
DR HPA; ENSG00000105245; Low tissue specificity.
DR MIM; 604018; gene.
DR neXtProt; NX_Q9Y6R0; -.
DR OpenTargets; ENSG00000105245; -.
DR PharmGKB; PA31846; -.
DR VEuPathDB; HostDB:ENSG00000105245; -.
DR eggNOG; KOG3537; Eukaryota.
DR GeneTree; ENSGT00940000160957; -.
DR InParanoid; Q9Y6R0; -.
DR OMA; YPPMPQV; -.
DR OrthoDB; 1110016at2759; -.
DR PhylomeDB; Q9Y6R0; -.
DR TreeFam; TF314159; -.
DR PathwayCommons; Q9Y6R0; -.
DR SignaLink; Q9Y6R0; -.
DR BioGRID-ORCS; 9253; 104 hits in 1079 CRISPR screens.
DR ChiTaRS; NUMBL; human.
DR EvolutionaryTrace; Q9Y6R0; -.
DR GeneWiki; NUMBL; -.
DR GenomeRNAi; 9253; -.
DR Pharos; Q9Y6R0; Tbio.
DR PRO; PR:Q9Y6R0; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9Y6R0; protein.
DR Bgee; ENSG00000105245; Expressed in pancreatic ductal cell and 184 other tissues.
DR ExpressionAtlas; Q9Y6R0; baseline and differential.
DR Genevisible; Q9Y6R0; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0034332; P:adherens junction organization; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0021670; P:lateral ventricle development; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0021849; P:neuroblast division in subventricular zone; ISS:UniProtKB.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0019538; P:protein metabolic process; IDA:UniProtKB.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR016698; Numb/numb-like.
DR InterPro; IPR010449; Numb_domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR PANTHER; PTHR47368; PTHR47368; 1.
DR Pfam; PF06311; NumbF; 1.
DR Pfam; PF00640; PID; 1.
DR PIRSF; PIRSF017607; Numb/numb-like; 1.
DR SMART; SM00462; PTB; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Developmental protein; Neurogenesis;
KW Phosphoprotein; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..609
FT /note="Numb-like protein"
FT /id="PRO_0000057999"
FT DOMAIN 74..223
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 223..283
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 434..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 537..609
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..29
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..68
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 434..451
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..573
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08919"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:3F0W"
FT HELIX 67..74
FT /evidence="ECO:0007829|PDB:3F0W"
FT STRAND 78..91
FT /evidence="ECO:0007829|PDB:3F0W"
FT HELIX 96..107
FT /evidence="ECO:0007829|PDB:3F0W"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:3F0W"
FT STRAND 122..129
FT /evidence="ECO:0007829|PDB:3F0W"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:3F0W"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:3F0W"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:3F0W"
FT STRAND 144..149
FT /evidence="ECO:0007829|PDB:3F0W"
FT STRAND 156..163
FT /evidence="ECO:0007829|PDB:3F0W"
FT TURN 164..167
FT /evidence="ECO:0007829|PDB:3F0W"
FT STRAND 168..179
FT /evidence="ECO:0007829|PDB:3F0W"
FT HELIX 181..201
FT /evidence="ECO:0007829|PDB:3F0W"
SQ SEQUENCE 609 AA; 64891 MW; 69458D161B60F4B4 CRC64;
MSRSAAASGG PRRPERHLPP APCGAPGPPE TCRTEPDGAG TMNKLRQSLR RRKPAYVPEA
SRPHQWQADE DAVRKGTCSF PVRYLGHVEV EESRGMHVCE DAVKKLKAMG RKSVKSVLWV
SADGLRVVDD KTKDLLVDQT IEKVSFCAPD RNLDKAFSYI CRDGTTRRWI CHCFLALKDS
GERLSHAVGC AFAACLERKQ RREKECGVTA AFDASRTSFA REGSFRLSGG GRPAEREAPD
KKKAEAAAAP TVAPGPAQPG HVSPTPATTS PGEKGEAGTP VAAGTTAAAI PRRHAPLEQL
VRQGSFRGFP ALSQKNSPFK RQLSLRLNEL PSTLQRRTDF QVKGTVPEME PPGAGDSDSI
NALCTQISSS FASAGAPAPG PPPATTGTSA WGEPSVPPAA AFQPGHKRTP SEAERWLEEV
SQVAKAQQQQ QQQQQQQQQQ QQQQQQAASV APVPTMPPAL QPFPAPVGPF DAAPAQVAVF
LPPPHMQPPF VPAYPGLGYP PMPRVPVVGI TPSQMVANAF CSAAQLQPQP ATLLGKAGAF
PPPAIPSAPG SQARPRPNGA PWPPEPAPAP APELDPFEAQ WAALEGKATV EKPSNPFSGD
LQKTFEIEL
