CBLB (gene)

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Protein CBLB PDB 2ooa.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases CBLB, Cbl-b, RNF56, Nbla00127, Cbl proto-oncogene B
External IDs MGI: 2146430 HomoloGene: 15856 GeneCards: CBLB
RNA expression pattern
PBB GE CBLB 209682 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC) Chr 3: 105.66 – 105.87 Mb Chr 16: 52.03 – 52.21 Mb
PubMed search [1] [2]
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CBL-B is an E3 ubiquitin-protein ligase that in humans is encoded by the CBLB gene.[3][4] CBLB is a member of the CBL gene family.


CBL-B functions as a negative regulator of T-cell activation.[5] CBL-B expression in T cells causes ligand-induced T cell receptor down-modulation, controlling the activation degree of T cells during antigen presentation.[6][7]

Clinical significance[edit]

Mutation of the CBLB gene has been associated with autoimmune conditions such as type 1 diabetes.[8][9]


CBLB has been shown to interact with:


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Keane MM, Rivero-Lezcano OM, Mitchell JA, Robbins KC, Lipkowitz S (July 1995). "Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene". Oncogene. 10 (12): 2367–77. PMID 7784085. 
  4. ^ "Entrez Gene: CBLB Cas-Br-M (murine) ecotropic retroviral transforming sequence b". 
  5. ^ Wallner S, Gruber T, Baier G, Wolf D (2012). "Releasing the brake: targeting Cbl-b to enhance lymphocyte effector functions". Clin. Dev. Immunol. 2012: 692639. PMC 3328896Freely accessible. PMID 22550535. doi:10.1155/2012/692639. 
  6. ^ Naramura M, Jang IK, Kole H, Huang F, Haines D, Gu H (August 2002). "Pc-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation.". Nature Immunology. 3 (12): 1192–9. PMID 12415267. doi:10.1038/ni855. 
  7. ^ Karwacz K, Bricogne C, MacDonald D, Arce F, Bennett CL, Collins M, Escors D (August 2011). "PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells". EMBO Molecular Medicine. 3 (10): 581–92. PMC 3191120Freely accessible. PMID 21739608. doi:10.1002/emmm.201100165. 
  8. ^ Hoyne GF, Flening E, Yabas M, Teh C, Altin JA, Randall K, Thien CB, Langdon WY, Goodnow CC (February 2011). "Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to type 1 diabetes". J. Immunol. 186 (4): 2024–32. PMID 21248249. doi:10.4049/jimmunol.1002296. 
  9. ^ Yokoi N, Fujiwara Y, Wang HY, Kitao M, Hayashi C, Someya T, Kanamori M, Oiso Y, Tajima N, Yamada Y, Seino Y, Ikegami H, Seino S (March 2008). "Identification and functional analysis of CBLB mutations in type 1 diabetes". Biochem. Biophys. Res. Commun. 368 (1): 37–42. PMID 18201552. doi:10.1016/j.bbrc.2008.01.032. 
  10. ^ a b c Elly C, Witte S, Zhang Z, Rosnet O, Lipkowitz S, Altman A, Liu YC (February 1999). "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation". Oncogene. 18 (5): 1147–56. PMID 10022120. doi:10.1038/sj.onc.1202411. 
  11. ^ Schulze WX, Deng L, Mann M (2005). "Phosphotyrosine interactome of the ErbB-receptor kinase family". Mol. Syst. Biol. 1: 2005.0008. PMC 1681463Freely accessible. PMID 16729043. doi:10.1038/msb4100012. 
  12. ^ Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S (March 1999). "cbl-b inhibits epidermal growth factor receptor signaling". Oncogene. 18 (10): 1855–66. PMID 10086340. doi:10.1038/sj.onc.1202499. 
  13. ^ a b Lavagna-Sévenier C, Marchetto S, Birnbaum D, Rosnet O (June 1998). "The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor signal transduction in pro-B cells". J. Biol. Chem. 273 (24): 14962–7. PMID 9614102. doi:10.1074/jbc.273.24.14962. 
  14. ^ Magnifico A, Ettenberg S, Yang C, Mariano J, Tiwari S, Fang S, Lipkowitz S, Weissman AM (October 2003). "WW domain HECT E3s target Cbl RING finger E3s for proteasomal degradation". J. Biol. Chem. 278 (44): 43169–77. PMID 12907674. doi:10.1074/jbc.M308009200. 
  15. ^ Szymkiewicz I, Kowanetz K, Soubeyran P, Dinarina A, Lipkowitz S, Dikic I (October 2002). "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases". J. Biol. Chem. 277 (42): 39666–72. PMID 12177062. doi:10.1074/jbc.M205535200. 

External links[edit]

Further reading[edit]