SH3KBP1
Function
Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation (PubMed:29636373).
Involvement in disease
Immunodeficiency 61
IMD61
An X-linked recessive primary immunologic disorder characterized by recurrent infections due to impaired antibody production. Affected individuals have normal numbers of circulating B and T cells, but B cells have an intrinsic defect in antibody production. Disease severity is variable and onset is in early childhood.
None
The disease may be caused by variants affecting the gene represented in this entry.
Post-translational modifications
Monoubiquitinated by CBL and CBLB after EGF stimulation; probably on its C-terminus.
Tissue Specificity
Ubiquitously expressed. Also expressed in some cancer cell lines.
Cellular localization
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Cytoplasmic vesicle membrane
- Peripheral membrane protein
- Synapse
- Synaptosome
- Cell junction
- Focal adhesion
- Localized in endocytic vesicles containing clustered receptors. Colocalizes with ASAP1 in vesicular structures. Colocalized with actin microfilaments and focal adhesions (By similarity). Colocalized with MAGI2 in synaptosomes. Translocation to EGFR containing vesicles upon EGF stimulation is inhibited in the presence of SH3KBP1 (By similarity). Colocalizes with ZFP36 in the cytoplasm (PubMed:20221403).
Alternative names
CIN85, SH3KBP1, SH3 domain-containing kinase-binding protein 1, CD2-binding protein 3, Cbl-interacting protein of 85 kDa, Human Src family kinase-binding protein 1, CD2BP3, HSB-1