Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage Cell Signaling Technology
Home | Login
About PhosphoSiteUsing PhosphoSiteprivacy & cookiesCuration ProcessContact
logos LINCs Logo Mt Sinai Logo NIH Logo NCI Logo
Search / Browse Functions
Protein Page:

Cbl-b 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. 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. May also be involved in EGFR ubiquitination and internalization. Interacts 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. Expressed 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. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Adaptor/scaffold; Calcium-binding; EC 6.3.2.-; Ligase; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of Human Ortholog: 3q13.11
Cellular Component: cytosol; lipid raft; nucleoplasm; plasma membrane
Molecular Function: protein binding; receptor tyrosine kinase binding; SH3 domain binding; zinc ion binding
Biological Process: epidermal growth factor receptor signaling pathway; negative regulation of epidermal growth factor receptor activity; NLS-bearing substrate import into nucleus; proteolysis; signal transduction
Reference #:  Q13191 (UniProtKB)
Alt. Names/Synonyms: Cas-Br-M (murine) ecotropic retroviral transforming sequence b; Cas-Br-M (murine) ectropic retroviral transforming sequence b; Casitas B-lineage lymphoma proto-oncogene b; Cbl-b; CBLB; DKFZp686J10223; DKFZp779A0729; DKFZp779F1443; E3 ubiquitin-protein ligase CBL-B; FLJ36865; FLJ41152; Nbla00127; RING finger protein 56; RNF56; SH3-binding protein CBL-B; Signal transduction protein CBL-B
Gene Symbols: CBLB
Molecular weight: 109,450 Da
Basal Isoelectric point: 8.15  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  Insulin Receptor Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below


Protein Structure Not Found.
Download PyMol Script
Download ChimeraX Script

STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Scansite  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene