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Numb-like protein

 NUMBL_RAT               Reviewed;         614 AA.
A1L1I3;
23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
06-FEB-2007, sequence version 1.
23-MAY-2018, entry version 75.
RecName: Full=Numb-like protein;
Name=Numbl; Synonyms=Nbl;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Brown Norway;
Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Heart;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
INTERACTION WITH NUMBL.
PubMed=18299187; DOI=10.1016/j.cellsig.2008.01.015;
Ma Q., Zhou L., Shi H., Huo K.;
"NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced
NF-kappaB activation.";
Cell. Signal. 20:1044-1051(2008).
[4]
INTERACTION WITH NUMBL.
PubMed=20079715; DOI=10.1016/j.bbrc.2010.01.037;
Zhou L., Ma Q., Shi H., Huo K.;
"NUMBL interacts with TRAF6 and promotes the degradation of TRAF6.";
Biochem. Biophys. Res. Commun. 392:409-414(2010).
[5]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22673903; DOI=10.1038/ncomms1871;
Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
Lundby C., Olsen J.V.;
"Quantitative maps of protein phosphorylation sites across 14
different rat organs and tissues.";
Nat. Commun. 3:876-876(2012).
-!- 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 (By similarity).
{ECO:0000250}.
-!- SUBUNIT: Associates with EPS15 and NOTCH1 (By similarity).
Interacts (via PTB domain) with MAP3K7IP2 (via C-terminal).
Interacts (via C-terminal) with TRAF6 (via TRAF domains).
{ECO:0000250, ECO:0000269|PubMed:18299187,
ECO:0000269|PubMed:20079715}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Note=Symmetrically
distributed throughout the cytoplasm in non dividing neuroblasts
of the CNS. {ECO:0000250}.
-!- DOMAIN: The PTB domain is necessary for the inhibition of
MAP3K7IP2-mediated activation of NF-kappa-B. {ECO:0000250}.
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EMBL; CH473979; EDM07964.1; -; Genomic_DNA.
EMBL; BC129073; AAI29074.1; -; mRNA.
RefSeq; XP_006228629.1; XM_006228567.3.
UniGene; Rn.15133; -.
ProteinModelPortal; A1L1I3; -.
SMR; A1L1I3; -.
BioGrid; 253944; 2.
STRING; 10116.ENSRNOP00000054039; -.
iPTMnet; A1L1I3; -.
PaxDb; A1L1I3; -.
PeptideAtlas; A1L1I3; -.
PRIDE; A1L1I3; -.
Ensembl; ENSRNOT00000057213; ENSRNOP00000054039; ENSRNOG00000020867.
GeneID; 292732; -.
UCSC; RGD:1307579; rat.
CTD; 9253; -.
RGD; 1307579; Numbl.
eggNOG; KOG3537; Eukaryota.
eggNOG; ENOG410XT15; LUCA.
GeneTree; ENSGT00530000062937; -.
HOVERGEN; HBG006672; -.
InParanoid; A1L1I3; -.
PhylomeDB; A1L1I3; -.
TreeFam; TF314159; -.
PRO; PR:A1L1I3; -.
Proteomes; UP000002494; Chromosome 1.
Bgee; ENSRNOG00000020867; -.
ExpressionAtlas; A1L1I3; baseline and differential.
Genevisible; A1L1I3; RN.
GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
GO; GO:0021670; P:lateral ventricle development; ISS:UniProtKB.
GO; GO:0021849; P:neuroblast division in subventricular zone; ISS:UniProtKB.
GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IMP:RGD.
GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB.
GO; GO:0019538; P:protein metabolic process; ISS:UniProtKB.
Gene3D; 2.30.29.30; -; 1.
InterPro; IPR016698; Numb/numb-like.
InterPro; IPR010449; Numb_domain.
InterPro; IPR011993; PH-like_dom_sf.
InterPro; IPR006020; PTB/PI_dom.
Pfam; PF06311; NumbF; 1.
Pfam; PF00640; PID; 1.
PIRSF; PIRSF017607; Numb/numb-like; 1.
SMART; SM00462; PTB; 1.
PROSITE; PS01179; PID; 1.
1: Evidence at protein level;
Complete proteome; Cytoplasm; Developmental protein; Neurogenesis;
Phosphoprotein; Reference proteome; Ubl conjugation pathway.
CHAIN 1 614 Numb-like protein.
/FTId=PRO_0000393007.
DOMAIN 74 223 PID. {ECO:0000255|PROSITE-
ProRule:PRU00148}.
COMPBIAS 422 451 Gln-rich.
COMPBIAS 456 581 Pro-rich.
MOD_RES 224 224 Phosphoserine.
{ECO:0000250|UniProtKB:Q9Y6R0}.
MOD_RES 228 228 Phosphoserine.
{ECO:0000250|UniProtKB:Q9Y6R0}.
MOD_RES 263 263 Phosphoserine.
{ECO:0000250|UniProtKB:Q9Y6R0}.
MOD_RES 279 279 Phosphothreonine.
{ECO:0000250|UniProtKB:Q9Y6R0}.
MOD_RES 411 411 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
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


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