UniProt functional annotation for Q8R550



	UniProt functional annotation for Q8R550

UniProt code: Q8R550.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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 (By similarity). Has an essential role in the stimulation of B cell activation (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q96B97}.

Subunit: Can self-associate and form homotetramers. Interacts with CD2, F-actin capping protein, PIK3R3, GRB2, EGFR, MET, BLNK, MAP3K4, PDCD6IP, SPRY2, ARHGAP17, ARHGAP27, CRK, BCAR1, SOS1, ASAP1, ARAP3, HIP1R, SYNJ2, INPP5D and STAP1 (By similarity). Interacts with CBL (PubMed:21830225). Interacts with CBLB, but does not interact with CBLC. Two molecules of SH3KBP1 seem to bind through their respective SH3 1 domain to one molecule of CBLB. The interaction with CBL or CBLB and EGFR is increased upon EGF stimulation. The interaction with CBL is attenuated by PDCD6IP. Interacts through its proline-rich region with the SH3 domain of endophilins SH3GL1, SH3GL2 and SH3GL3. The SH3KBP1- endophilin complex seems to associate with a complex containing the phosphorylated receptor (EGFR or MET) and phosphorylated CBL. Probably associates with ASAP1 and phosphorylated EGFR. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3. Interacts with focal adhesion kinases PTK2/FAK1 AND PTK2B/PYK2, probably as a dimer. Interacts with DAB2 and probably associates with chathrin through its interaction with DAB2. Part of a complex consisting of SH3KBP1, DAB2, and clathrin heavy chain. DAB2 and clathrin dissociate from SH3KBP1 following growth factor treatment, enabling interaction with CBL. Interacts with DDN and probably associates with MAGI2 through its interaction with DDN. Interacts with the SH3 domains of SRC tyrosine- protein kinases SRC, LCK, LYN, FGR, FYN and HCK. Interacts with TRADD, BIRC2, TRAF1, TRAF2 and TNFR1, and the association with a TNFR1- associated complex upon stimulation with TNF-alpha seems to be mediated by SRC. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3 (By similarity). Interacts (via SH3 domains) with SHKBP1 (via PXXXPR motifs) (PubMed:11152963, PubMed:21830225). Interacts with ATX2 (PubMed:18602463). Interaction with CBL is abolished in the presence of SHKBP1 (PubMed:21830225). Interacts (via SH3 domains) with ZFP36 (via extreme C-terminal region). Interacts with MAP3K4; this interaction enhances the association with ZFP36 (By similarity). {ECO:0000250|UniProtKB:Q96B97, ECO:0000269|PubMed:11152963, ECO:0000269|PubMed:18602463, ECO:0000269|PubMed:21830225}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q96B97}. Cytoplasm, cytoskeleton {ECO:0000250}. Cytoplasmic vesicle membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cell junction, synapse, synaptosome {ECO:0000250}. Cell junction, focal adhesion {ECO:0000250}. Note=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 (By similarity). Translocation to EGFR containing vesicles upon EGF stimulation is inhibited in the presence of SH3KBP1 (PubMed:21830225). Colocalizes with ZFP36 in the cytoplasm (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q96B97, ECO:0000269|PubMed:21830225}.

Ptm: Monoubiquitinated by CBL and CBLB after EGF stimulation; probably on its C-terminus. {ECO:0000250}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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 (By similarity). Has an essential role in the stimulation of B cell activation (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:Q96B97}.


Subunit:		Can self-associate and form homotetramers. Interacts with CD2, F-actin capping protein, PIK3R3, GRB2, EGFR, MET, BLNK, MAP3K4, PDCD6IP, SPRY2, ARHGAP17, ARHGAP27, CRK, BCAR1, SOS1, ASAP1, ARAP3, HIP1R, SYNJ2, INPP5D and STAP1 (By similarity). Interacts with CBL (PubMed:21830225). Interacts with CBLB, but does not interact with CBLC. Two molecules of SH3KBP1 seem to bind through their respective SH3 1 domain to one molecule of CBLB. The interaction with CBL or CBLB and EGFR is increased upon EGF stimulation. The interaction with CBL is attenuated by PDCD6IP. Interacts through its proline-rich region with the SH3 domain of endophilins SH3GL1, SH3GL2 and SH3GL3. The SH3KBP1- endophilin complex seems to associate with a complex containing the phosphorylated receptor (EGFR or MET) and phosphorylated CBL. Probably associates with ASAP1 and phosphorylated EGFR. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3. Interacts with focal adhesion kinases PTK2/FAK1 AND PTK2B/PYK2, probably as a dimer. Interacts with DAB2 and probably associates with chathrin through its interaction with DAB2. Part of a complex consisting of SH3KBP1, DAB2, and clathrin heavy chain. DAB2 and clathrin dissociate from SH3KBP1 following growth factor treatment, enabling interaction with CBL. Interacts with DDN and probably associates with MAGI2 through its interaction with DDN. Interacts with the SH3 domains of SRC tyrosine- protein kinases SRC, LCK, LYN, FGR, FYN and HCK. Interacts with TRADD, BIRC2, TRAF1, TRAF2 and TNFR1, and the association with a TNFR1- associated complex upon stimulation with TNF-alpha seems to be mediated by SRC. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3 (By similarity). Interacts (via SH3 domains) with SHKBP1 (via PXXXPR motifs) (PubMed:11152963, PubMed:21830225). Interacts with ATX2 (PubMed:18602463). Interaction with CBL is abolished in the presence of SHKBP1 (PubMed:21830225). Interacts (via SH3 domains) with ZFP36 (via extreme C-terminal region). Interacts with MAP3K4; this interaction enhances the association with ZFP36 (By similarity). {ECO:0000250\|UniProtKB:Q96B97, ECO:0000269\|PubMed:11152963, ECO:0000269\|PubMed:18602463, ECO:0000269\|PubMed:21830225}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:Q96B97}. Cytoplasm, cytoskeleton {ECO:0000250}. Cytoplasmic vesicle membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cell junction, synapse, synaptosome {ECO:0000250}. Cell junction, focal adhesion {ECO:0000250}. Note=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 (By similarity). Translocation to EGFR containing vesicles upon EGF stimulation is inhibited in the presence of SH3KBP1 (PubMed:21830225). Colocalizes with ZFP36 in the cytoplasm (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:Q96B97, ECO:0000269\|PubMed:21830225}.
Ptm:		Monoubiquitinated by CBL and CBLB after EGF stimulation; probably on its C-terminus. {ECO:0000250}.