ITSN1

The protein encoded by this gene is a cytoplasmic membrane-associated protein that indirectly coordinates endocytic membrane traffic with the actin assembly machinery. In addition, the encoded protein may regulate the formation of clathrin-coated vesicles and could be involved in synaptic vesicle recycling. This protein has been shown to interact with dynamin, CDC42, SNAP23, SNAP25, SPIN90, EPS15, EPN1, EPN2, and STN2. Multiple transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been characterized so far. [provided by RefSeq]

Full Name

intersectin 1 (SH3 domain protein)

Function

Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery (PubMed:11584276, PubMed:29887380).
Acts as guanine nucleotide exchange factor (GEF) for CDC42, and thereby stimulates actin nucleation mediated by WASL and the ARP2/3 complex (PubMed:11584276).
Plays a role in the assembly and maturation of clathrin-coated vesicles (By similarity).
Recruits FCHSD2 to clathrin-coated pits (PubMed:29887380).
Involved in endocytosis of activated EGFR, and probably also other growth factor receptors (By similarity).
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 (PubMed:22648170).
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 (By similarity).
Inhibits ARHGAP31 activity toward RAC1 (PubMed:11744688).
Isoform 1
Plays a role in synaptic vesicle endocytosis in brain neurons.

Biological Process

Cellular protein localizationManual Assertion Based On ExperimentIMP:UniProtKB
Clathrin-dependent synaptic vesicle endocytosisManual Assertion Based On ExperimentIBA:GO_Central
EndocytosisManual Assertion Based On ExperimentIBA:GO_Central
Endosomal transportManual Assertion Based On ExperimentIBA:GO_Central
ExocytosisIEA:UniProtKB-KW
Intracellular signal transductionIEA:InterPro
Protein transportIEA:UniProtKB-KW
Regulation of small GTPase mediated signal transductionTAS:Reactome

Cellular Location

Endomembrane system; Cell junction, synapse, synaptosome; Cell projection, lamellipodium; Cell membrane; Membrane, clathrin-coated pit; Recycling endosome; Endosome; Cytoplasmic vesicle. Colocalizes with SGIP1 at the plasma membrane in structures corresponding most probably to clathrin-coated pits (PubMed:20946875).
Colocalizes with RAB13 on cytoplasmic vesicles that are most likely recycling endosomes (PubMed:29030480).
Isoform 2: Cytoplasm; Endomembrane system; Nucleus envelope. Shuttles between the cytoplasm and nucleus in an XPO1/CRM1-dependent manner.
Isoform 5: Endomembrane system