ITSN1
Domain
SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains, bind to dynamin (By similarity). SH3-1 and SH3-4 bind to ARHGAP31.
The KLERQ domain binds to SNAP-25 and SNAP-23.
In an autoinhibited form the SH3 domain 5 may bind intramolecularly to the DH domain, thus blocking the CDC42-binding site.
Function
Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery (PubMed:11584276, PubMed:29887380). Acts as a 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.
Tissue Specificity
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:11690630, PubMed:21712076, PubMed:9799604).
Cellular localization
- Endomembrane system
- 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
Alternative names
ITSN, SH3D1A, ITSN1, Intersectin-1, SH3 domain-containing protein 1A, SH3P17