CBL
entrez
867
canonical
uniprot
P22681
canonical
ensembl
ENSG00000110395
resolver
ensp
ENSP00000264033
resolver
enst
ENST00000264033
resolver
genesymbol
CBL
resolver
genesymbol_syn
CBL2
resolver
genesymbol_syn
RNF55
resolver
hgnc
HGNC:1541
resolver
uniprot
A3KMP8
resolver
uniprot_entry
CBL_HUMAN
resolver
uniprot_sec
A3KMP8
resolver
amino_acid_sequence
MAGNVKKSSGAGGGSGSGGSGSGGLIGLMKDAFQPHHHHHHHLSPHPPGTVDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTILSRYEGKMETLGENEYFRVFMENLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQGDTFRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGRNQNPDLTGLCEPTPQDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPFDPRGSGSLLRQGAEGAPSPNYDDDDDERADDTLFMMKELAGAKVERPPSPFSMAPQASLPPVPPRLDLLPQRVCVPSSASALGTASKAASGSLHKDKPLPVPPTLRDLPPPPPPDRPYSVGAESRPQRRPLPCTPGDCPSRDKLPPVPSSRLGDSWLPRPIPKVPVSAPSSSDPWTGRELTNRHSLPFSLPSQMEPRPDVPRLGSTFSLDTSMSMNSSPLVGPECDHPKIKPSSSANAIYSLAARPLPVPKLPPGEQCEGEEDTEYMTPSSRPLRPLDTSQSSRACDCDQQIDSCTYEAMYNIQSQAPSITESSTFGEGNLAAAHANTGPEESENEDDGYDVPKPPVPAVLARRTLSDISNASSSFGWLSLDGDPTTNVTEGSQVPERPPKPFPRRINSERKAGSCQQGSGPAASAATASPQLSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFVSISSPAHVAT
uniprot
proteins
disease_involvement
DISEASE: Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:613563]: A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia. {ECO:0000269|PubMed:20619386, ECO:0000269|PubMed:25178484}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors (PubMed:10514377, PubMed:11896602, PubMed:14661060, PubMed:14739300, PubMed:15190072, PubMed:17509076, PubMed:18374639, PubMed:19689429, PubMed:21596750, PubMed:28381567, PubMed:40101708). Accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome (PubMed:10514377, PubMed:14661060, PubMed:14739300, PubMed:17094949, PubMed:17509076, PubMed:17974561). Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and mediates their ubiquitination to terminate signaling (PubMed:15190072, PubMed:18374639, PubMed:21596750). Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation (PubMed:11896602). Ubiquitinates EGFR and SPRY2 (PubMed:17094949, PubMed:17974561). Involved in LAG3-mediated inhibition of TCR signaling: following ligand-binding to LAG3, catalyzes 'Lys-63'-linked ubiquitination of LAG3, unleashing the LAG3 C-terminus from the membrane, and initiating a signaling that prevents TCR activation (PubMed:40101708). Ubiquitinates NECTIN1 following association between NECTIN1 and herpes simplex virus 1/HHV-1 envelope glycoprotein D, leading to NECTIN1 removal from cell surface (PubMed:28381567). Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis (PubMed:15190072, PubMed:18374639). Essential for osteoclastic bone resorption (PubMed:14739300). The 'Tyr-731' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14739300). In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity). {ECO:0000250|UniProtKB:P22682, ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:17094949, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19689429, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:28381567, ECO:0000269|PubMed:40101708}.
uniprot
proteins
mass_dalton
99633
uniprot
proteins
mutagenesis
MUTAGEN 80; /note="S->D: Abolishes interaction with ZAP70."; /evidence="ECO:0000269|PubMed:10078535"; MUTAGEN 82; /note="P->A: Abolishes interaction with ZAP70."; /evidence="ECO:0000269|PubMed:10078535"; MUTAGEN 229; /note="D->Q: Abolishes interaction with ZAP70."; /evidence="ECO:0000269|PubMed:10078535"; MUTAGEN 240; /note="E->S: Abolishes interaction with ZAP70."; /evidence="ECO:0000269|PubMed:10078535"; MUTAGEN 294; /note="R->K: Abolishes interaction with ZAP70."; /evidence="ECO:0000269|PubMed:10078535"; MUTAGEN 306; /note="G->E: Abolishes interaction with ZAP70 and EPHB1, but does not affect interaction with SLA. Reduces ubiquitination and therefore proteasomal degradation of SPRED2."; /evidence="ECO:0000269|PubMed:10078535, ECO:0000269|PubMed:10449770, ECO:0000269|PubMed:17094949"; MUTAGEN 371; /note="Y->F: Strongly reduces tyrosine phosphorylation by INSR; when associated with F-700 and F-774."; /evidence="ECO:0000269|PubMed:11997497"; MUTAGEN 381; /note="C->A: Loss of ubiquitin ligase activity."; /evidence="ECO:0000269|PubMed:11896602"; MUTAGEN 674; /note="Y->F: Does not affect interaction with TNS4 following EGF stimulation."; /evidence="ECO:0000269|PubMed:23774213"; MUTAGEN 700; /note="Y->F: Does not affect interaction with TNS4 following EGF stimulation. Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-774."; /evidence="ECO:0000269|PubMed:11997497, ECO:0000269|PubMed:23774213"; MUTAGEN 731; /note="Y->F: No effect on tyrosine phosphorylation by INSR. Loss of phosphorylation by SRC. Inhibition of bone resorption. Abolishes interaction with PIK3R1. Does not affect interaction with TNS4 following EGF stimulation."; /evidence="ECO:0000269|PubMed:11997497, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:23774213"; MUTAGEN 774; /note="Y->F: Loss of interaction with TNS4 following EGF stimulation. Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-700."; /evidence="ECO:0000269|PubMed:11997497, ECO:0000269|PubMed:23774213
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:28381567, ECO:0000269|PubMed:40101708}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues by ALK, EGFR, SYK, FYN and ZAP70 (By similarity). Phosphorylated on tyrosine residues in response to FLT1 and KIT signaling. Phosphorylated on tyrosine residues by INSR and FGR. Phosphorylated on several tyrosine residues by constitutively activated FGFR3. Not phosphorylated at Tyr-731 by FGFR3. Phosphorylated on tyrosine residues by activated CSF1R, PDGFRA and PDGFRB. Phosphorylated on tyrosine residues by HCK. {ECO:0000250, ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:11850825, ECO:0000269|PubMed:11997497, ECO:0000269|PubMed:12435267, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:20494825, ECO:0000269|PubMed:20622007, ECO:0000269|PubMed:26848865, ECO:0000269|PubMed:7657591, ECO:0000269|PubMed:9535867}.; PTM: Ubiquitinated, leading to its degradation via the proteasome (PubMed:11896602, PubMed:20094046). Ubiquitination is negatively regulated by IFT20 (PubMed:29237719). {ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:20094046, ECO:0000269|PubMed:29237719}.
uniprot
proteins
pubmed
10078535
uniprot
proteins
pubmed
10092522
uniprot
proteins
pubmed
10374881
uniprot
proteins
pubmed
10449770
uniprot
proteins
pubmed
10514377
uniprot
proteins
pubmed
10966114
uniprot
proteins
pubmed
11067845
uniprot
proteins
pubmed
11696592
uniprot
proteins
pubmed
11850825
uniprot
proteins
pubmed
11896602
uniprot
proteins
pubmed
11997497
uniprot
proteins
pubmed
12435267
uniprot
proteins
pubmed
12486104
uniprot
proteins
pubmed
12504111
uniprot
proteins
pubmed
12522270
uniprot
proteins
pubmed
14661060
uniprot
proteins
pubmed
14739300
uniprot
proteins
pubmed
15144186
uniprot
proteins
pubmed
15190072
uniprot
proteins
pubmed
15226403
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15526160
uniprot
proteins
pubmed
15556646
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
15958209
uniprot
proteins
pubmed
16129412
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17094949
uniprot
proteins
pubmed
17509076
uniprot
proteins
pubmed
17620338
uniprot
proteins
pubmed
17974561
uniprot
proteins
pubmed
18034775
uniprot
proteins
pubmed
18235045
uniprot
proteins
pubmed
18374639
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19689429
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19836242
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20094046
uniprot
proteins
pubmed
2030914
uniprot
proteins
pubmed
20494825
uniprot
proteins
pubmed
20619386
uniprot
proteins
pubmed
20622007
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21596750
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23376399
uniprot
proteins
pubmed
23774213
uniprot
proteins
pubmed
25000980
uniprot
proteins
pubmed
25178484
uniprot
proteins
pubmed
26848865
uniprot
proteins
pubmed
28381567
uniprot
proteins
pubmed
29237719
uniprot
proteins
pubmed
30118682
uniprot
proteins
pubmed
40101708
uniprot
proteins
pubmed
7657591
uniprot
proteins
pubmed
8083187
uniprot
proteins
pubmed
9407100
uniprot
proteins
pubmed
9535867
uniprot
proteins
pubmed
9989826
uniprot
proteins
sequence_length
906
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Cell membrane {ECO:0000269|PubMed:40101708}. Cell projection, cilium {ECO:0000269|PubMed:29237719}. Golgi apparatus {ECO:0000269|PubMed:29237719}. Note=Colocalizes with FGFR2 in lipid rafts at the cell membrane.
uniprot
proteins