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MGP000429

UniProt Annotations

Entry Information
Gene NameCbl proto-oncogene B, E3 ubiquitin protein ligase
Protein EntryCBLB_HUMAN
UniProt IDQ13191
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=Long; IsoId=Q13191-1; Sequence=Displayed; Name=Truncated 1; IsoId=Q13191-2; Sequence=VSP_005729; Name=Truncated 2; IsoId=Q13191-3; Sequence=VSP_005730, VSP_005731;
DomainThe N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.
DomainThe RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.
DomainThe UBA domain interacts with poly-ubiquitinated proteins.
FunctionE3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. 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. {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694}.
InteractionQ9ULH1:ASAP1; NbExp=2; IntAct=EBI-744027, EBI-346622; Q9Y5K6:CD2AP; NbExp=11; IntAct=EBI-744027, EBI-298152; P62993:GRB2; NbExp=5; IntAct=EBI-744027, EBI-401755; P16333:NCK1; NbExp=4; IntAct=EBI-744027, EBI-389883; Q96B97:SH3KBP1; NbExp=19; IntAct=EBI-744027, EBI-346595;
MiscellaneousThis protein has one functional calcium-binding site. {ECO:0000250}.
PathwayProtein modification; protein ubiquitination.
PtmAuto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation. {ECO:0000269|PubMed:11375397}.
PtmPhosphorylated 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:18669648, ECO:0000269|PubMed:19549985, ECO:0000269|PubMed:20525694}.
Sequence CautionSequence=BAE45748.1; Type=Erroneous termination; Positions=904; Note=Translated as Arg.; Evidence={ECO:0000305}; Sequence=CAH56175.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
SimilarityContains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain. {ECO:0000255|PROSITE-ProRule:PRU00839}.
SimilarityContains 1 RING-type zinc finger. {ECO:0000255|PROSITE-ProRule:PRU00175}.
SimilarityContains 1 UBA domain. {ECO:0000255|PROSITE- ProRule:PRU00212}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:12177062}. Note=Upon EGF stimulation, associates with endocytic vesicles.
SubunitInteracts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. May interact with CBL. Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts with EGFR (phosphorylated). {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:15273720, ECO:0000269|PubMed:16228008, ECO:0000269|PubMed:17020880, ECO:0000269|PubMed:17679095, ECO:0000269|PubMed:9399639, ECO:0000269|Ref.26}.
Tissue SpecificityExpressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes (at protein level). {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:9399639}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CBLbID193.html";
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