E3 ubiquitin-protein ligase CBL-B; Casitas B-lineage lymphoma proto-oncogene b; RING finger protein 56; SH3-binding protein CBL-B; signal transduction protein CBL-B (CBLB, RNF56, Nbla00127)

Function

• E3 ubiquitin-protein ligase, ubiquitin conjugation 3rd step
• negatively regulates
  • TCR (T-cell receptor)
  • BCR (B-cell receptor)
  • FCER1 (high affinity Ig epsilon receptor)
  • inhibits VAV1 activation upon TCR engagement in naive T-cells
    • necessitates CD28 costimulation for proliferation & IL-2 production
  • promotes PIK3R1 ubiquitination
  • promotes anergy in activated T-cells
    • inhibits PLCG1 activation
    • inhibits Ca+2 mobilization
  • ubiquitinates SYK in B-cells, promotes proteasomal degradation
  • EGFR ubiquitination & internalization
  • auto-ubiquitinated upon:
    • EGF-mediated cell activation
    • T-cell costimulation by CD28
  • phosphorylated on Tyr upon TCR or BCR activation, & upon various types of cell stimulation
  • interactions:
    • SH3 domain-containing proteins
      • LCK, CRK, SORBS1m, LCP2, ZAP70, CBL, VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1, SH3KBP1
    • poly-ubiquitinated proteins

Structure

• UBA domain interacts with poly-ubiquitinated proteins

Compartment

• cytoplasm
• associates with endocytic vesicles with EGF stimulation

Alternative splicing

named isoforms=4

Expression

• expressed in placenta, heart, lung, kidney, spleen, ovary, testis, fetal brain, liver, hematopoietic cell lines
• not expressed in adult brain, liver, pancreas, salivary gland, or skeletal muscle

More general terms

• E3 ubiquitin ligase
• ring finger protein
• phosphoprotein
• Ca+2 binding protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=868
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:868
• OMIM: https://mirror.omim.org/entry/604491
• UniProt: http://www.uniprot.org/uniprot/Q13191.html