InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CBLB

Summary

InnateDB Protein

IDBP-48444.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CBLB

Protein Name

Cas-Br-M (murine) ecotropic retroviral transforming sequence b

Synonyms

Cbl-b; RNF56;

Species

Homo sapiens

Ensembl Protein

ENSP00000264122

InnateDB Gene

IDBG-48442 (CBLB)

Protein Structure

UniProt Annotation

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. 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:0000269PubMed:10022120, ECO:0000269PubMed:10086340, ECO:0000269PubMed:11087752, ECO:0000269PubMed:11526404, ECO:0000269PubMed:14661060, ECO:0000269PubMed:20525694}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:12177062}. Note=Upon EGF stimulation, associates with endocytic vesicles.

Disease Associations

Tissue Specificity

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). {ECO:0000269PubMed:10022120, ECO:0000269PubMed:9399639}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 79 experimentally validated interaction(s) in this database.
They are also associated with 20 interaction(s) predicted by orthology.

Experimentally validated
Total	79 [view]
Protein-Protein	79 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	20 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001784	phosphotyrosine binding
GO:0004842	ubiquitin-protein transferase activity
GO:0004871	signal transducer activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0046872	metal ion binding

Biological Process

GO:0002669	positive regulation of T cell anergy
GO:0006607	NLS-bearing protein import into nucleus
GO:0006955	immune response
GO:0007165	signal transduction
GO:0007166	cell surface receptor signaling pathway
GO:0016567	protein ubiquitination
GO:0035556	intracellular signal transduction
GO:0042110	T cell activation
GO:0045732	positive regulation of protein catabolic process
GO:0046642	negative regulation of alpha-beta T cell proliferation
GO:0050860	negative regulation of T cell receptor signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000449 Ubiquitin-associated domain/translation elongation factor EF-Ts, N-terminal
IPR000980 SH2 domain
IPR001841 Zinc finger, RING-type
IPR003153 Adaptor protein Cbl, N-terminal helical
IPR009060 UBA-like
IPR014741 Adaptor protein Cbl, EF hand-like
IPR014742 Adaptor protein Cbl, SH2-like
IPR015940 Ubiquitin-associated/translation elongation factor EF1B, N-terminal, eukaryote
IPR018957 Zinc finger, C3HC4 RING-type

PFAM