UniProt:Q13191 CBLB

chain
  • chain:1-982
checksum B4E307D31B9F0779
comment
  • FUNCTION 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 (PubMed:20525694, PubMed:40101708). Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways (PubMed:40101708). In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production (By similarity). Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation (PubMed:11087752, PubMed:11526404). In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy (By similarity). Involved in LAG3-mediated inhibition of TCR signaling: following ligand-binding to LAG3, catalyzes 'Lys-63'-linked ubiquitination of LAG3, unleashing the LAG3 C-terminus from the membrane, and initiating a signaling that prevents TCR activation (PubMed:39030301, PubMed:40101708). In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation (By similarity). Slightly promotes SRC ubiquitination (PubMed:14661060). May be involved in EGFR ubiquitination and internalization (PubMed:10086340). 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 (By similarity).CATALYTIC ACTIVITY S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. Interacts with CBL (PubMed:29237719). 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). Interacts with IFT20 (PubMed:29237719).INTERACTION Upon EGF stimulation, associates with endocytic vesicles.ALTERNATIVE PRODUCTS 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 (at protein level).INDUCTION By serum starvation.DOMAIN The 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.DOMAIN The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.DOMAIN The UBA domain interacts with poly-ubiquitinated proteins.PTM Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation.PTM Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS This protein has one functional calcium-binding site.SEQUENCE CAUTION Truncated C-terminus.SEQUENCE CAUTION Probable cloning artifact.
created [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
crossReference
databaseName UniProt
dbId 405572
description
  • recommendedName: E3 ubiquitin-protein ligase CBL-B ecNumber evidence="15 22"2.3.2.27 alternativeName: Casitas B-lineage lymphoma proto-oncogene b alternativeName: RING finger protein 56 alternativeName: fullName evidence="30"RING-type E3 ubiquitin transferase CBL-B alternativeName: SH3-binding protein CBL-B alternativeName: Signal transduction protein CBL-B
displayName UniProt:Q13191 CBLB
geneName
  • CBLB
  • RNF56
  • Nbla00127
identifier Q13191
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • Calcium
  • Cytoplasm
  • Disease variant
  • Metal-binding
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Repeat
  • Transferase
  • Ubl conjugation
  • Ubl conjugation pathway
  • Zinc
  • Zinc-finger
modified [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType Protein
name
  • CBLB
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • CBLB_HUMAN
  • A8K9S7
  • B7WNM4
  • Q13192
  • Q13193
  • Q3LIC0
  • Q63Z43
  • Q8IVC5
sequenceLength 982
species [Species:48887] Homo sapiens
stId uniprot:Q13191
url http://purl.uniprot.org/uniprot/Q13191
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