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: 21q22.11
Cellular Component:  clathrin-coated pit; cytoplasm; cytosol; intracellular vesicle; lamellipodium; neuron projection; nuclear envelope; plasma membrane; presynaptic membrane; recycling endosome
Molecular Function:  calcium ion binding; guanyl-nucleotide exchange factor activity; molecular adaptor activity; proline-rich region binding; protein binding
Biological Process:  clathrin-dependent synaptic vesicle endocytosis; endosomal transport; exocytosis; intracellular signal transduction; protein localization; protein transport; regulation of small GTPase mediated signal transduction
Reference #:  Q15811 (UniProtKB)
Alt. Names/Synonyms: human intersectin-SH3 domain-containing protein SH3P17; intersectin 1; intersectin 1 (SH3 domain protein); intersectin 1 short form variant 11; intersectin 1 short form variant 3; intersectin 1 short form variant, 11; intersectin short variant 12; Intersectin-1; ITSN; ITSN1; MGC134948; MGC134949; SH3 domain protein-1A; SH3 domain-containing protein 1A; SH3D1A; SH3P17; Src homology 3 domain-containing protein
Gene Symbols: ITSN1
Molecular weight: 195,422 Da
Basal Isoelectric point: 7.76  Predict pI for various phosphorylation states
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  InnateDB  |  Ensembl Protein