SH3 domain-containing kinase-binding protein 1; CD2-binding protein 3; CD2BP3; Cbl-interacting protein of 85 kDa; Human Src family kinase-binding protein 1; HSB-1 (SH3KBP1 CIN85)
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Function
- adapter protein
- role in regulating diverse signal transduction pathways
- role in regulation of endocytosis & lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR & MET through an association with CBL & endophilins
- association with CBL, & thus the receptor internalization, may be inhibited by an interaction with PDCD6IP &/or SPRY2
- role in regulation of ligand-dependent endocytosis of the IgE receptor
- attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (putative)
- may be involved in regulation of cell adhesion
- promotes interaction between TTK2B & PDCD6IP
- may play role in regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4
- role in modulation of TNF-mediated apoptosis
- role in regulation of cell morphology & cytoskeletal organization
- required in control of cell shape & migration
- monoubiquitinated by CBL & CBLB after EGF stimulation probably on its C-terminus
- can self-associate & form homotetramers
- interacts with CD2, F-actin capping protein, PIK3R3, GRB2, EGFR, MET, BLNK, MAP3K4, PDCD6IP, SPRY2, ARHGAP17, ARHGAP27, MAGI2, CRK, BCAR1, SOS1, ASAP1, ARAP3, HIP1R, SYNJ2, INPP5D & STAP1
- interacts with CBL & CBLB
- does not interact with CBLC
- 2 SH3KBP1 seem to bind through their respective SH3 1 domain to 1 CBLB
- interaction with CBL or CBLB & EGFR is increased upon EGF stimulation
- interaction with CBL is attenuated by PDCD6IP
- interacts through its proline-rich region with the SH3 domain of endophilins SH3GL1, SH3GL2 & SH3GL3
- the SH3KBP1-endophilin complex seems to associate with a complex containing the phosphorylated receptor (EGFR or MET) & phosphorylated CBL
- probably associates with ASAP1 & phosphorylated EGFR
- probably part of a complex consisting of at least SH3KBP1, ASAP1 & ARAP3
- interacts with focal adhesion kinases PTK2/FAK1 & PTK2B/PYK2, probably as a dimer
- interacts with DAB2 & probably associates with chathrin through its interaction with DAB2
- part of a complex consisting of SH3KBP1, DAB2, & clathrin heavy chain
- DAB2 & clathrin dissociate from SH3KBP1 following growth factor treatment, enabling interaction with CBL
- interacts with DDN & probably associates with MAGI2 through its interaction with DDN.
- interacts with the SH3 domains of SRC tyrosine-protein kinases SRC, LCK, LYN, FGR, FYN & HCK
- interacts with TRADD, BIRC2, TRAF1, TRAF2 & TNFR1
- association with a TNFR1-associated complex upon stimulation with TNF-alpha seems to be mediated by SRC
- probably interacts with SH3KBP1
- interacts with CD2 cytoplasmic tail
- does not interact with F-actin
Structure
- the SH3 domains mediate interaction with SHKBP1
- contains 3 SH3 domains
Compartment
- cytoplasm, cytoskeleton, cytoplasmic vesicle
- peripheral membrane protein
- cell junction, focal adhesion (putative)
- synapse, synaptosome
- localized in endocytic vesicles containing clustered receptors
- colocalizes with ASAP1 in vesicular structures
- colocalized with actin microfilaments & focal adhesions
- colocalized with MAGI2 in synaptosomes
Alternative splicing
named isoforms=2
Expression
- ubiquitously expressed
- expressed in some cancer cell lines