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:10064583). Acts as a guanine nucleotide exchange factor (GEF) for CDC42, and thereby stimulates actin nucleation mediated by WASL and the ARP2/3 complex (By similarity). Plays a role in the assembly and maturation of clathrin-coated vesicles (By similarity). Recruits FCHSD2 to clathrin-coated pits (By similarity). Involved in endocytosis of activated EGFR, and probably also other growth factor receptors (PubMed:16914641). 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 (By similarity). Promotes ubiquitination and subsequent degradation of EGFR, and thereby contributes to the down-regulation of EGFR-dependent signaling pathways (PubMed:16914641). In chromaffin cells, required for normal exocytosis of catecholamines (PubMed:18676989). Required for rapid replenishment of release-ready synaptic vesicles at presynaptic active zones (PubMed:23633571). Inhibits ARHGAP31 activity toward RAC1 (By similarity).

Isoform 1

Plays a role in synaptic vesicle endocytosis in brain neurons.

Tissue Specificity

Detected in brain, adrenal gland and heart (PubMed:16914641, PubMed:18676989). Detected in neurons at the calyx of Held (at protein level) (PubMed:23633571). Isoform 1: Primarily detected in brain neurons. Isoform 2: Primarily detected in glia (at protein level) (PubMed:18676989). Widely expressed. Expressed at high levels in brain, heart and skeletal muscle (PubMed:10064583).

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. Colocalizes with RAB13 on cytoplasmic vesicles that are most likely recycling endosomes.
• Isoform 2
• Cytoplasm
• Nucleus envelope
• Shuttles between the cytoplasm and nucleus in an XPO1/CRM1-dependent manner.

Alternative names

Ese1, Itsn, Itsn1, Intersectin-1, EH and SH3 domains protein 1

Database links

swissprot:Q9Z0R4