CBLB
entrez
868
canonical
uniprot
Q13191
canonical
ensembl
ENSG00000114423
resolver
ensp
ENSP00000377598
resolver
ensp
ENSP00000494383
resolver
ensp
ENSP00000496761
resolver
ensp
ENSP00000526837
resolver
ensp
ENSP00000526839
resolver
ensp
ENSP00000526840
resolver
ensp
ENSP00000526844
resolver
ensp
ENSP00000526845
resolver
ensp
ENSP00000712162
resolver
genesymbol
CBLB
resolver
genesymbol_syn
RNF56
resolver
hgnc
HGNC:1542
resolver
uniprot
A8K9S7
resolver
uniprot
B3KSS7
resolver
uniprot
B4DYP3
resolver
uniprot
B7WNM4
resolver
uniprot
B7ZAG1
resolver
uniprot
Q13192
resolver
uniprot
Q13193
resolver
uniprot
Q3LIC0
resolver
uniprot
Q63Z43
resolver
uniprot
Q8IVC5
resolver
uniprot_entry
B3KSS7_HUMAN
resolver
uniprot_entry
B4DYP3_HUMAN
resolver
uniprot_entry
B7ZAG1_HUMAN
resolver
uniprot_entry
CBLB_HUMAN
resolver
uniprot_sec
A8K9S7
resolver
uniprot_sec
B7WNM4
resolver
uniprot_sec
Q13192
resolver
uniprot_sec
Q13193
resolver
uniprot_sec
Q3LIC0
resolver
uniprot_sec
Q63Z43
resolver
uniprot_sec
Q8IVC5
resolver
amino_acid_sequence
MANSMNGRNPGGRGGNPRKGRILGIIDAIQDAVGPPKQAAADRRTVEKTWKLMDKVVRLCQNPKLQLKNSPPYILDILPDTYQHLRLILSKYDDNQKLAQLSENEYFKIYIDSLMKKSKRAIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHMLAEIKAIFPNGQFQGDNFRITKADAAEFWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWGSILRNWNFLAVTHPGYMAFLTYDEVKARLQKYSTKPGSYIFRLSCTRLGQWAIGYVTGDGNILQTIPHNKPLFQALIDGSREGFYLYPDGRSYNPDLTGLCEPTPHDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTAWQESDGQGCPFCRCEIKGTEPIIVDPFDPRDEGSRCCSIIDPFGMPMLDLDDDDDREESLMMNRLANVRKCTDRQNSPVTSPGSSPLAQRRKPQPDPLQIPHLSLPPVPPRLDLIQKGIVRSPCGSPTGSPKSSPCMVRKQDKPLPAPPPPLRDPPPPPPERPPPIPPDNRLSRHIHHVESVPSRDPPMPLEAWCPRDVFGTNQLVGCRLLGEGSPKPGITASSNVNGRHSRVGSDPVLMRKHRRHDLPLEGAKVFSNGHLGSEEYDVPPRLSPPPPVTTLLPSIKCTGPLANSLSEKTRDPVEEDDDEYKIPSSHPVSLNSQPSHCHNVKPPVRSCDNGHCMLNGTHGPSSEKKSNIPDLSIYLKGDVFDSASDPVPLPPARPPTRDNPKHGSSLNRTPSDYDLLIPPLGEDAFDALPPSLPPPPPPARHSLIEHSKPPGSSSRPSSGQDLFLLPSDPFVDLASGQVPLPPARRLPGENVKTNRTSQDYDQLPSCSDGSQAPARPPKPRPRRTAPEIHHRKPHGPEAALENVDAKIAKLMGEGYAFEEVKRALEIAQNNVEVARSILREFAFPPPVSPRLNL
uniprot
proteins
disease_involvement
DISEASE: Autoimmune disease, multisystem, infantile-onset, 3 (ADMIO3) [MIM:620430]: An autosomal recessive disorder characterized by autoimmune manifestations apparent in the first months or years of life. Clinical features may include hypothyroidism, type 1 diabetes mellitus, systemic inflammatory manifestations such as fever and hepatomegaly, and autoimmune cytopenias. {ECO:0000269|PubMed:36006710}. 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 which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome (PubMed:20525694, PubMed:40101708). Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways (PubMed:40101708). In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production (By similarity). Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation (PubMed:11087752, PubMed:11526404). In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy (By similarity). 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:39030301, PubMed:40101708). In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation (By similarity). Slightly promotes SRC ubiquitination (PubMed:14661060). May be involved in EGFR ubiquitination and internalization (PubMed:10086340). May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, 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:Q3TTA7, ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:39030301, ECO:0000269|PubMed:40101708}.
uniprot
proteins
mass_dalton
109450
uniprot
proteins
mutagenesis
MUTAGEN 298; /note="G->E: Inhibits interaction with SYK. No effect on E3 activity."; /evidence="ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:11087752"; MUTAGEN 363; /note="Y->E: Decreases affinity for E2 ubiquitin-conjugating enzymes."; /evidence="ECO:0000269|PubMed:20525694"; MUTAGEN 373; /note="C->A: Abolishes E3 activity but does not affect binding to substrates."; /evidence="ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11375397"; MUTAGEN 665; /note="Y->F: Slightly inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-709."; /evidence="ECO:0000269|PubMed:10022120"; MUTAGEN 709; /note="Y->F: Inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-665."; /evidence="ECO:0000269|PubMed:10022120"; MUTAGEN 904; /note="R->A: No effect on interaction with CD2AP. Reduced interaction with SH3KBP1. Strongly reduced interaction with SH3KBP1; when associated with A-911."; /evidence="ECO:0000269|PubMed:16228008, ECO:0000269|PubMed:17020880"; MUTAGEN 907; /note="K->A: No effect on interaction with SH3KBP1. Reduced interaction with CD2AP. Strongly reduced interaction with CD2AP; when associated with A-911."; /evidence="ECO:0000269|PubMed:17020880"; MUTAGEN 911; /note="R->A: Reduced interaction with CD2AP and with SH3KBP1. Strongly reduced interaction with CD2AP; when associated with A-907. Strongly reduced interaction with SH3KBP1; when associated with A-904."; /evidence="ECO:0000269|PubMed:16228008, ECO:0000269|PubMed:17020880"; MUTAGEN 937; /note="A->E: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation."; /evidence="ECO:0000269|PubMed:17679095"; MUTAGEN 940; /note="M->A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation."; /evidence="ECO:0000269|PubMed:17679095"; MUTAGEN 943..944; /note="GY->AQ: Abolishes interaction with ubiquitinated proteins."; /evidence="ECO:0000269|PubMed:15273720"; MUTAGEN 946; /note="F->A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation."; /evidence="ECO:0000269|PubMed:17679095"; MUTAGEN 966; /note="I->E: Interferes with dimerization. Reduced E3 ubiquitin-protein ligase activity. Reduced levels of tyrosine phosphorylation."; /evidence="ECO:0000269|PubMed:17679095"; MUTAGEN 967; /note="L->A: No effect on interaction with ubiquitinated proteins."; /evidence="ECO:0000269|PubMed:15273720
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:40101708}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation. {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:19549985, ECO:0000269|PubMed:20525694}.; PTM: Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation. {ECO:0000269|PubMed:11375397}.
uniprot
proteins
pubmed
10022120
uniprot
proteins
pubmed
10086340
uniprot
proteins
pubmed
11087752
uniprot
proteins
pubmed
11375397
uniprot
proteins
pubmed
11526404
uniprot
proteins
pubmed
12177062
uniprot
proteins
pubmed
12880961
uniprot
proteins
pubmed
14661060
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15273720
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16228008
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
17020880
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17679095
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19549985
uniprot
proteins
pubmed
20525694
uniprot
proteins
pubmed
29237719
uniprot
proteins
pubmed
36006710
uniprot
proteins
pubmed
39030301
uniprot
proteins
pubmed
40101708
uniprot
proteins
pubmed
7784085
uniprot
proteins
pubmed
9399639
uniprot
proteins
sequence_length
982
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12177062}. Note=Upon EGF stimulation, associates with endocytic vesicles.
uniprot
proteins