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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.
05-JUN-2019, entry version 81.
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.
SMR; A1L1I3; -.
BioGrid; 253944; 3.
STRING; 10116.ENSRNOP00000054039; -.
iPTMnet; A1L1I3; -.
jPOST; 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; ENSGT00940000160957; -.
InParanoid; A1L1I3; -.
OrthoDB; 1110016at2759; -.
PhylomeDB; A1L1I3; -.
TreeFam; TF314159; -.
PRO; PR:A1L1I3; -.
Proteomes; UP000002494; Chromosome 1.
Bgee; ENSRNOG00000020867; Expressed in 9 organ(s), highest expression level in brain.
ExpressionAtlas; A1L1I3; baseline and differential.
Genevisible; A1L1I3; RN.
GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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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WP1650: Fluorobenzoate degradation
WP2218: sGC
WP1887: Post-translational modification: synthesis of GPI-anchored proteins
WP1165: G Protein Signaling Pathways
WP1693: Purine metabolism
WP912: Notch Signaling Pathway
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WP1032: NLR proteins
WP1659: Glycine, serine and threonine metabolism
WP232: G Protein Signaling Pathways
WP1963: The effect of Glucocorticoids on target gene expression
WP1357: Notch Signaling Pathway
WP265: Delta-Notch Signaling Pathway
WP288: NLR proteins
WP1438: Influenza A virus infection
WP1892: Protein folding
WP1239: Cytoplasmic Ribosomal Proteins
WP1665: Limonene and pinene degradation
WP1360: NLR proteins
WP1675: Nitrogen metabolism
WP346: Protein Modifications
WP477: Cytoplasmic Ribosomal Proteins
WP1531: Vitamin D synthesis
WP199: Delta-Notch Signaling Pathway
WP73: G Protein Signaling Pathways

Related Genes :

Bibliography :
[28974699] NUMBL Interacts with TAK1, TRAF6 and NEMO to Negatively Regulate NF-κB Signaling During Osteoclastogenesis.
[27613838] Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like properties and resistance to chemotherapy.
[26069237] Regulation of vascular endothelial growth factor receptor function in angiogenesis by numb and numb-like.
[25535389] Osteopetrosis in TAK1-deficient mice owing to defective NF-κB and NOTCH signaling.
[24335256] Numb family proteins are essential for cardiac morphogenesis and progenitor differentiation.
[23440423] Regulation of lung cancer metastasis by Klf4-Numb-like signaling.
[21150807] Expression of Numb and Numb-like in the development of mammalian auditory sensory epithelium.
[19944684] The multiple functions of Numb.
[17589506] Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors.
[16865239] NUMB is a break of WNT-Notch signaling cycle.