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)

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

Properties

SIZE: entity length = 665 aa MW = 73 kD COMPARTMENT: cytoplasm MOTIF: src homology 3 [SH3] domain SITE: 1-58 src homology 3 [SH3] domain SITE: 98-157 MOTIF: Ser phosphorylation site {S156} Ser phosphorylation site {S230} Thr phosphorylation site {T254} src homology 3 [SH3] domain SITE: 267-328 proline-rich region SITE: 327-428 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S436} Ser phosphorylation site {S509} Ser phosphorylation site {S511} Ser phosphorylation site {S521} Ser phosphorylation site {S587} coiled coil {602-664}

Database Correlations

OMIM 300374 UniProt Q96B97 PFAM correlations Entrez Gene 30011 Kegg hsa:30011

References

UniProt :accession Q96B97