ID Q9WVE9; PN Intersectin-1; GN Itsn1; OS 10116; SL Nucleus Position: SL-0178; SL Comments: 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}. [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}. DR UNIPROT: Q9WVE9; DR UNIPROT: D3ZV52; DR UNIPROT: F1M823; DR UNIPROT: Q9WVE1; DR PDB: 3HS9; DR Pfam: PF00168; DR Pfam: PF12763; DR Pfam: PF16617; DR Pfam: PF16652; DR Pfam: PF00621; DR Pfam: PF00018; DR Pfam: PF07653; DR Pfam: PF14604; DR PROSITE: PS50004; DR PROSITE: PS00741; DR PROSITE: PS50010; DR PROSITE: PS00018; DR PROSITE: PS50222; DR PROSITE: PS50031; DR PROSITE: PS50003; DR PROSITE: PS50002; DE 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 (PubMed:20448150). 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 (PubMed:23633571). Inhibits ARHGAP31 activity toward RAC1 (By similarity). {ECO:0000250|UniProtKB:Q15811, ECO:0000250|UniProtKB:Q9Z0R4, ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:23633571}. [Isoform 1]: Plays a role in synaptic vesicle endocytosis in brain neurons. {ECO:0000250|UniProtKB:Q9Z0R4}. DE Reference Proteome: Yes; DE Interaction: P60881; IntAct: EBI-7031678; Score: 0.60 DE Interaction: E9PSY8; IntAct: EBI-10919034; Score: 0.40 DE Interaction: P21575; IntAct: EBI-7031625; Score: 0.56 DE Interaction: O70377; IntAct: EBI-7031784; Score: 0.44 DE Interaction: P14668; IntAct: EBI-8589490; Score: 0.27 DE Interaction: Q3UQN2; IntAct: EBI-6095200; Score: 0.35 DE Interaction: Q5XIE8; IntAct: EBI-26440627; Score: 0.35 GO GO:0070161; GO GO:0097440; GO GO:0044305; GO GO:0005905; GO GO:0005737; GO GO:0043197; GO GO:0030139; GO GO:0098978; GO GO:0097708; GO GO:0030027; GO GO:0043025; GO GO:0005635; GO GO:0005886; GO GO:0098871; GO GO:0098833; GO GO:0055037; GO GO:0045202; GO GO:0043195; GO GO:0005509; GO GO:0005085; GO GO:0019209; GO GO:0060090; GO GO:0070064; GO GO:0007420; GO GO:0150007; GO GO:0006897; GO GO:0016197; GO GO:0006887; GO GO:0043524; GO GO:0051402; GO GO:2001288; GO GO:0060999; GO GO:0060124; GO GO:0051897; GO GO:0008104; GO GO:0015031; GO GO:1905274; GO GO:0007264; GO GO:0048488; TP Membrane Topology: Unknown; Source: UniProt - Sequence Analysis; SQ MAQFPTPFGGSLDIWAITVEERAKHDQQFQSLKPISGFITGDQARNFFFQSGLPQPVLAQIWALADMNKDGRMDQVEFSI SQ AMKLIKLKLQGYQLPPALPPVMKQQPAAISSAPAFGIGGMAGMPPLTAVAPVPMGSIPVVGMSPPLVSSVPQAAVPPLAN SQ GAPPVIQPLPAFAHPAATLPKSSSFSRSGPGSQLNTKLQKAQSFDVASAPAAAEWAVPQSSRLKYRQLFNSHDKTMSGHL SQ TGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMSGQPLPPVLPPEYIPPSFRRVRSGSGMSVI SQ SSSSADQRLPEEPSSEDEQQVEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQ SQ ERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLTQRNKDQEGIVVLKARRKTLEFE SQ LEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLH SQ RDSLLTLKRALEAKELARQQLREQLDEVEKETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSIEAERLKQKEQERKSLE SQ LEKQKEEGQRRVQERDKQWQEHVQQEEQQRPRKPHEEDKLKREDSVKKKEAEERAKPEVQDKQSRLFHPHQEPAKPAQAP SQ WPTTEKGPLTISAQESAKVVYYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEKIPENE SQ IPTPAKPVTDLTSAPAPKLALRETPAPLPVTSSEPSTTPNNWADFSSTWPSSTNEKPETDNWDTWAAQPSLTVPSAGQLR SQ QRSAFTPATATGSSPSPVLGQGEKVEGLQAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL SQ ISGPVRKSTSIDTGPTEAPSSLKRVASPAAKPAIPGEEFVAMYTYESSEHGDLTFQQGDVIVVTKKDGDWWTGTVGETSG SQ VFPSNYVRLKDSEGSGTAGKTGSLGKKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWF SQ PANYVKLLSPGTSKITPTELPKTAVQPAVCQVIGMYDYTAQNDDELAFSKGQIINVLSKEDPDWWKGEVSGQVGLFPSNY SQ VKLTTDMDPSQQWCSDLHLLDMLTPTERKRQGYIHELIVTEENYVNDLQLVTEIFQKPLTESELLTEKEVAMIFVNWKEL SQ IMCNIKLLKALRVRKKMSGEKMPVKMIGDILSAQLPHMQPYIRFCSCQLNGAALIQQKTDEAPDFKEFVKRLAMDPRCKG SQ MPLSSFILKPMQRVTRYPLIIKNILENTPENHPDHSHLKHALEKAEELCSQVNEGVREKENSDRLEWIQAHVQCEGLSEQ SQ LVFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQITKPLGSSSTDKVFSPKSNLQYKMYKTPIFLNEVLVK SQ LPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKKKREKAYLVRSQRATGIGRLMVNVVEGIEL SQ KPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDFLGRTEIRVADIKKD SQ QGSKGPVTKCLLLHEVPTGEIVVRLDLQLFDEP //