General Information of Drug Therapeutic Target (DTT) (ID: TTGT3RQ)

DTT Name E3 ubiquitin protein ligase CBLB (CBLB)
Synonyms
Signal transduction protein CBLB; Signal transduction protein CBL-B; SH3binding protein CBLB; SH3-binding protein CBL-B; RNF56; RING-type E3 ubiquitin transferase CBL-B; RING finger protein 56; Nbla00127; E3 ubiquitinprotein ligase CBLB; E3 ubiquitin-protein ligase CBL-B; Casitas Blineage lymphoma protooncogene b; Casitas B-lineage lymphoma proto-oncogene b
Gene Name CBLB
DTT Type
Literature-reported target
[1]
BioChemical Class
Acyltransferase
UniProt ID
CBLB_HUMAN
TTD ID
T04393
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.3.2.27
Sequence
MANSMNGRNPGGRGGNPRKGRILGIIDAIQDAVGPPKQAAADRRTVEKTWKLMDKVVRLC
QNPKLQLKNSPPYILDILPDTYQHLRLILSKYDDNQKLAQLSENEYFKIYIDSLMKKSKR
AIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHMLAEIKAIFPNGQFQGDNFRITKADAAE
FWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLF
QPWGSILRNWNFLAVTHPGYMAFLTYDEVKARLQKYSTKPGSYIFRLSCTRLGQWAIGYV
TGDGNILQTIPHNKPLFQALIDGSREGFYLYPDGRSYNPDLTGLCEPTPHDHIKVTQEQY
ELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTAWQESDGQGCPFCRCEIKGTEP
IIVDPFDPRDEGSRCCSIIDPFGMPMLDLDDDDDREESLMMNRLANVRKCTDRQNSPVTS
PGSSPLAQRRKPQPDPLQIPHLSLPPVPPRLDLIQKGIVRSPCGSPTGSPKSSPCMVRKQ
DKPLPAPPPPLRDPPPPPPERPPPIPPDNRLSRHIHHVESVPSRDPPMPLEAWCPRDVFG
TNQLVGCRLLGEGSPKPGITASSNVNGRHSRVGSDPVLMRKHRRHDLPLEGAKVFSNGHL
GSEEYDVPPRLSPPPPVTTLLPSIKCTGPLANSLSEKTRDPVEEDDDEYKIPSSHPVSLN
SQPSHCHNVKPPVRSCDNGHCMLNGTHGPSSEKKSNIPDLSIYLKGDVFDSASDPVPLPP
ARPPTRDNPKHGSSLNRTPSDYDLLIPPLGEDAFDALPPSLPPPPPPARHSLIEHSKPPG
SSSRPSSGQDLFLLPSDPFVDLASGQVPLPPARRLPGENVKTNRTSQDYDQLPSCSDGSQ
APARPPKPRPRRTAPEIHHRKPHGPEAALENVDAKIAKLMGEGYAFEEVKRALEIAQNNV
EVARSILREFAFPPPVSPRLNL
Function
Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. 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. 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.
KEGG Pathway
ErbB signaling pathway (hsa04012 )
Ubiquitin mediated proteolysis (hsa04120 )
Endocytosis (hsa04144 )
C-type lectin receptor signaling pathway (hsa04625 )
T cell receptor signaling pathway (hsa04660 )
Insulin signaling pathway (hsa04910 )
Measles (hsa05162 )
Reactome Pathway
Antigen processing (R-HSA-983168 )

References

1 Targeting CBLB as a potential therapeutic approach for disseminated candidiasis. Nat Med. 2016 Aug;22(8):906-14.