Protein: Intersectin-1 (EH domain and SH3 domain regulator of endocytosis 1) (Q9WVE9)
Organism: Rattus norvegicus (Rat)
Function: 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 (By similarity). Plays a role in the assembly and maturation of clathrin-coated vesicles. Recruits FCHSD2 to clathrin-coated pits (By similarity). 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 (By similarity). 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 (By similarity). Required for rapid replenishment of release-ready synaptic vesicles at presynaptic active zones. Inhibits ARHGAP31 activity toward RAC1 (By similarity).
Subcellular location: Endomembrane system {ECO:0000250|UniProtKB:Q15811}. Synapse, synaptosome {ECO:0000269|PubMed:10373452, ECO:0000269|PubMed:26797119}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:Q15811}. Cell membrane {ECO:0000250|UniProtKB:Q15811}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:11584276, ECO:0000269|PubMed:20448150}. Recycling endosome {ECO:0000250|UniProtKB:Q15811}. Endosome {ECO:0000250|UniProtKB:Q9Z0R4}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q9Z0R4}. Note=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. {ECO:0000250|UniProtKB:Q15811}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000250|UniProtKB:Q15811}. Nucleus envelope {ECO:0000250|UniProtKB:Q15811}. Note=Shuttles between the cytoplasm and nucleus in an XPO1/CRM1-dependent manner. {ECO:0000250|UniProtKB:Q15811}.
Interaction partners:
- Cell division control protein 42 homolog
- Epidermal growth factor receptor pathway substrate 15
- AP-2 complex subunit alpha-2
- Epsin-1
- FCH and mu domain containing endocytic adaptor 1
- Actin nucleation-promoting factor WASL
- Epsin-2
- AP-2 complex subunit beta
- Stonin-2
- Dynamin-1
Sequence:
MAQFPTPFGGSLDIWAITVEERAKHDQQFQSLKPISGFITGDQARNFFFQSGLPQPVLAQIWALADMNKDGRMDQVEFSIAMKLIKLKLQGYQLPPALPPVMKQQPAAISSAPAFGIGGMAGMPPLTAVAPVPMGSIPVVGMSPPLVSSVPQAAVPPLANGAPPVIQPLPAFAHPAATLPKSSSFSRSGPGSQLNTKLQKAQSFDVASAPAAAEWAVPQSSRLKYRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMSGQPLPPVLPPEYIPPSFRRVRSGSGMSVISSSSADQRLPEEPSSEDEQQVEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLTQRNKDQEGIVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDEVEKETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSIEAERLKQKEQERKSLELEKQKEEGQRRVQERDKQWQEHVQQEEQQRPRKPHEEDKLKREDSVKKKEAEERAKPEVQDKQSRLFHPHQEPAKPAQAPWPTTEKGPLTISAQESAKVVYYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEKIPENEIPTPAKPVTDLTSAPAPKLALRETPAPLPVTSSEPSTTPNNWADFSSTWPSSTNEKPETDNWDTWAAQPSLTVPSAGQLRQRSAFTPATATGSSPSPVLGQGEKVEGLQAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQGQKGWFPKSYVKLISGPVRKSTSIDTGPTEAPSSLKRVASPAAKPAIPGEEFVAMYTYESSEHGDLTFQQGDVIVVTKKDGDWWTGTVGETSGVFPSNYVRLKDSEGSGTAGKTGSLGKKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLLSPGTSKITPTELPKTAVQPAVCQVIGMYDYTAQNDDELAFSKGQIINVLSKEDPDWWKGEVSGQVGLFPSNYVKLTTDMDPSQQWCSDLHLLDMLTPTERKRQGYIHELIVTEENYVNDLQLVTEIFQKPLTESELLTEKEVAMIFVNWKELIMCNIKLLKALRVRKKMSGEKMPVKMIGDILSAQLPHMQPYIRFCSCQLNGAALIQQKTDEAPDFKEFVKRLAMDPRCKGMPLSSFILKPMQRVTRYPLIIKNILENTPENHPDHSHLKHALEKAEELCSQVNEGVREKENSDRLEWIQAHVQCEGLSEQLVFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQITKPLGSSSTDKVFSPKSNLQYKMYKTPIFLNEVLVKLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKKKREKAYLVRSQRATGIGRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDFLGRTEIRVADIKKDQGSKGPVTKCLLLHEVPTGEIVVRLDLQLFDEP