Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery. Acts as guanine nucleotide exchange factor (GEF) for CDC42, and thereby stimulates actin nucleation mediated by WASL and the ARP2/3 complex. Plays a role in the assembly and maturation of clathrin-coated vesicles. Recruits FCHSD2 to clathrin-coated pits. Involved in endocytosis of activated EGFR, and probably also other growth factor receptors. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Promotes ubiquitination and subsequent degradation of EGFR, and thereby contributes to the down-regulation of EGFR-dependent signaling pathways. In chromaffin cells, required for normal exocytosis of catecholamines. Required for rapid replenishment of release-ready synaptic vesicles at presynaptic active zones. Inhibits ARHGAP31 activity toward RAC1. Isoform 1: Plays a role in synaptic vesicle endocytosis in brain neurons. Isoform 1 is expressed almost exclusively in the brain. Isoform 2 is detected in brain, spleen, lung, liver, heart, skeletal muscle and kidney. Isoform 5 is primarily expressed in brain, spleen, lung and kidney (at protein level) (PubMed:21712076). Isoform 1 and isoform 2 are detected in brain (PubMed:10482960). Isoform 2 is ubiquitous in adult and fetal tissues with high expression in skeletal muscle, heart, spleen, ovary, testis and all fetal tissues tested and low expression in thymus, blood, lung, liver and pancreas. Isoform 1 is expressed almost exclusively in the brain, in all brain regions. Not expressed in the spinal cord (PubMed:9799604, PubMed:21712076, PubMed:11690630). 13 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Adaptor/scaffold; Calcium-binding; GEF; GEF, Rac/Rho
Molecular Function: calcium ion binding; kinase activator activity; molecular adaptor activity; proline-rich region binding; protein binding; Rho guanyl-nucleotide exchange factor activity
Biological Process: brain development; cellular protein localization; exocytosis; negative regulation of neuron apoptotic process; positive regulation of caveolin-mediated endocytosis; positive regulation of dendritic spine development; positive regulation of growth hormone secretion; positive regulation of kinase activity; positive regulation of protein kinase B signaling; protein transport; regulation of modification of postsynaptic actin cytoskeleton; regulation of Rho protein signal transduction; small GTPase mediated signal transduction; synaptic vesicle endocytosis