ITSN1 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
Chromosomal Location of Human Ortholog: 16|16 C4
Cellular Component:  apical dendrite; calyx of Held; cell junction; cell projection; clathrin-coated pit; cytoplasm; cytoplasmic vesicle; dendritic spine; endocytic vesicle; endosome; glutamatergic synapse; intracellular vesicle; lamellipodium; membrane; neuron projection; neuronal cell body; nuclear envelope; nucleus; plasma membrane; postsynaptic actin cytoskeleton; presynaptic endocytic zone; synapse
Molecular Function:  calcium ion binding; guanyl-nucleotide exchange factor activity; kinase activator activity; metal ion binding; molecular adaptor activity; proline-rich region binding; protein binding; Rho guanyl-nucleotide exchange factor activity
Biological Process:  cellular protein localization; endocytosis; exocytosis; intracellular signal transduction; 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 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
Reference #:  Q9Z0R4 (UniProtKB)
Alt. Names/Synonyms: AA517634; AA545208; AI316805; AI839402; AI848451; EH and SH3 domains protein 1; Eh domain, SH3 domain regulator of endocytosis 1; EHSH; Ehsh1; Ese; Ese1; intersectin (SH3 domain protein 1A); intersectin 1 (SH3 domain protein 1A); intersectin short form 2 variant 2; Intersectin-1; intersectin-L; Itsn; Itsn1; OTTMUSP00000023652; Sh3p; Sh3p17
Gene Symbols: Itsn1
Molecular weight: 194,297 Da
Basal Isoelectric point: 8.05  Predict pI for various phosphorylation states
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Protein Structure Not Found.

Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene