NUMBL_RAT
ID NUMBL_RAT Reviewed; 614 AA.
AC A1L1I3;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Numb-like protein;
GN Name=Numbl; Synonyms=Nbl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 INTERACTION WITH NUMBL.
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 [4]
RP INTERACTION WITH NUMBL.
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Associates with EPS15 and NOTCH1 (By similarity). Interacts
CC (via PTB domain) with MAP3K7IP2 (via C-terminal). Interacts (via C-
CC terminal) with TRAF6 (via TRAF domains). {ECO:0000250,
CC ECO:0000269|PubMed:18299187, ECO:0000269|PubMed:20079715}.
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. {ECO:0000250}.
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DR EMBL; CH473979; EDM07964.1; -; Genomic_DNA.
DR EMBL; BC129073; AAI29074.1; -; mRNA.
DR RefSeq; XP_006228629.1; XM_006228567.3.
DR AlphaFoldDB; A1L1I3; -.
DR SMR; A1L1I3; -.
DR BioGRID; 253944; 3.
DR IntAct; A1L1I3; 1.
DR MINT; A1L1I3; -.
DR STRING; 10116.ENSRNOP00000054039; -.
DR iPTMnet; A1L1I3; -.
DR jPOST; A1L1I3; -.
DR PaxDb; A1L1I3; -.
DR PeptideAtlas; A1L1I3; -.
DR PRIDE; A1L1I3; -.
DR Ensembl; ENSRNOT00000057213; ENSRNOP00000054039; ENSRNOG00000020867.
DR GeneID; 292732; -.
DR UCSC; RGD:1307579; rat.
DR CTD; 9253; -.
DR RGD; 1307579; Numbl.
DR eggNOG; KOG3537; Eukaryota.
DR GeneTree; ENSGT00940000160957; -.
DR HOGENOM; CLU_031797_1_1_1; -.
DR InParanoid; A1L1I3; -.
DR PhylomeDB; A1L1I3; -.
DR TreeFam; TF314159; -.
DR PRO; PR:A1L1I3; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000020867; Expressed in frontal cortex and 18 other tissues.
DR ExpressionAtlas; A1L1I3; baseline and differential.
DR Genevisible; A1L1I3; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0034332; P:adherens junction organization; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; ISO:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0021670; P:lateral ventricle development; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0021849; P:neuroblast division in subventricular zone; ISS:UniProtKB.
DR GO; GO:0007405; P:neuroblast proliferation; ISO:RGD.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IMP:RGD.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0019538; P:protein metabolic process; ISS: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 Cytoplasm; Developmental protein; Neurogenesis; Phosphoprotein;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..614
FT /note="Numb-like protein"
FT /id="PRO_0000393007"
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 371..420
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 448..468
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 539..614
FT /note="Disordered"
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 547..578
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R0"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R0"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R0"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R0"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 614 AA; 65513 MW; 7703FA9E4925C238 CRC64;
MSRSAAASGG PRRPDQHLPP APCGASGPPE TFRTESDGAG TMNKLRQSLR RRKPAYVPEA
SRPHQWQADE DAVRKGTCSF PVRYLGHVEV EESRGMHVCE DAVKKLKAMG RKSVKSVLWV
SADGLRVVDD KTKDLLVDQT IEKVSFCAPD RNLDKAFSYI CRDGTTRRWI CHCFLALKDS
GERLSHAVGC AFAACLERKQ RREKECGVTA AFDASRTSFA REGSFRLSGG GRPAEREAGD
KKKAEAAAAP AVAPGPAQPG HVSPTPATTS PGEKGEAGTP VAAGTTAAAI PRRHAPLEQL
VRQGSFRGFP ALSQKNSPFK RQLSLRLNEL PSTLQRRTDF QVKGTVPEME PPGTGDSDGI
SALCTQISSS FASAGAPVPG PPSATTGTSA WGEPSVPAAT AFQPGHKRTP SEAERWLEEV
SQVAKAQQQQ QQQQQQQQQQ QQQQQQQQQQ QATSVPPMPT MAPTLQPFST PVGPFDTAAA
QVAVFLPPTH MQPPFVPAYP GLGYPPMPRV PVVGITPSQM VANAFCSAAQ LQPQPATLLG
KAGAFPPPTA PSAPGGQARP RPNGAPWPPE PAPAPAPELD PFEAQWAALE GKPAVEKPSN
PFSGDLQKTF EIEL
