Protein: Intersectin-1 (SH3 domain-containing protein 1A) (SH3P17) (Q15811)
Organism: Homo sapiens (Human)
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. Plays a role in the assembly and maturation of clathrin-coated vesicles (By similarity). Recruits FCHSD2 to clathrin-coated pits. 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. 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.
Subcellular location: Endomembrane system {ECO:0000269|PubMed:11744688}. Synapse, synaptosome {ECO:0000250|UniProtKB:Q9WVE9}. Cell projection, lamellipodium {ECO:0000269|PubMed:11744688}. Cell membrane {ECO:0000269|PubMed:11744688, ECO:0000269|PubMed:20946875}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:20946875, ECO:0000269|PubMed:29887380}. Recycling endosome {ECO:0000269|PubMed:29030480}. 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 (PubMed:20946875). Colocalizes with RAB13 on cytoplasmic vesicles that are most likely recycling endosomes (PubMed:29030480). {ECO:0000269|PubMed:20946875, ECO:0000269|PubMed:29030480}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:29599122}. Endomembrane system {ECO:0000269|PubMed:21712076}. Nucleus envelope {ECO:0000269|PubMed:29599122}. Note=Shuttles between the cytoplasm and nucleus in an XPO1/CRM1-dependent manner. {ECO:0000269|PubMed:29599122}.; SUBCELLULAR LOCATION: [Isoform 5]: Endomembrane system {ECO:0000269|PubMed:21712076}.
Sequence: MAQFPTPFGGSLDIWAITVEERAKHDQQFHSLKPISGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQVEFSIAMKLIKLKLQGYQLPSALPPVMKQQPVAISSAPAFGMGGIASMPPLTAVAPVPMGSIPVVGMSPTLVSSVPTAAVPPLANGAPPVIQPLPAFAHPAATLPKSSSFSRSGPGSQLNTKLQKAQSFDVASVPPVAEWAVPQSSRLKYRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMSGQPLPPVLPPEYIPPSFRRVRSGSGISVISSTSVDQRLPEEPVLEDEQQQLEKKLPVTFEDKKRENFERGNLELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEDIVVLKAKKKTLEFELEALNDKKHQLEGKLQDIRCRLTTQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILNDQLKQVQQNSLHRDSLVTLKRALEAKELARQHLRDQLDEVEKETRSKLQEIDIFNNQLKELREIHNKQQLQKQKSMEAERLKQKEQERKIIELEKQKEEAQRRAQERDKQWLEHVQQEDEHQRPRKLHEEEKLKREESVKKKDGEEKGKQEAQDKLGRLFHQHQEPAKPAVQAPWSTAEKGPLTISAQENVKVVYYRALYPFESRSHDEITIQPGDIVMVKGEWVDESQTGEPGWLGGELKGKTGWFPANYAEKIPENEVPAPVKPVTDSTSAPAPKLALRETPAPLAVTSSEPSTTPNNWADFSSTWPTSTNEKPETDNWDAWAAQPSLTVPSAGQLRQRSAFTPATATGSSPSPVLGQGEKVEGLQAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKLISGPIRKSTSMDSGSSESPASLKRVASPAAKPVVSGEEFIAMYTYESSEQGDLTFQQGDVILVTKKDGDWWTGTVGDKAGVFPSNYVRLKDSEGSGTAGKTGSLGKKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLLSPGTSKITPTEPPKSTALAAVCQVIGMYDYTAQNDDELAFNKGQIINVLNKEDPDWWKGEVNGQVGLFPSNYVKLTTDMDPSQQWCSDLHLLDMLTPTERKRQGYIHELIVTEENYVNDLQLVTEIFQKPLMESELLTEKEVAMIFVNWKELIMCNIKLLKALRVRKKMSGEKMPVKMIGDILSAQLPHMQPYIRFCSRQLNGAALIQQKTDEAPDFKEFVKRLAMDPRCKGMPLSSFILKPMQRVTRYPLIIKNILENTPENHPDHSHLKHALEKAEELCSQVNEGVREKENSDRLEWIQAHVQCEGLSEQLVFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQITKPLGSSGTDKVFSPKSNLQYKMYKTPIFLNEVLVKLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKKKREKAYLVRSQRATGIGRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDFLGRTEIRVADIKKDQGSKGPVTKCLLLHEVPTGEIVVRLDLQLFDEP
InterPro domains: - IPR000219: Dbl homology domain (domain) [1237-1423]
- IPR035892: C2 domain superfamily (homologous_superfamily) [1594-1719]
- IPR001849: Pleckstrin homology domain (domain) [1440-1593]
- IPR000261: EH domain (domain) [14-310]
- IPR036028: SH3-like domain superfamily (homologous_superfamily) [740-1219]
- IPR000008: C2 domain (domain) [1579-1695]
- IPR001452: SH3 domain (domain) [740-1214]
- IPR001331: Guanine-nucleotide dissociation stimulator, CDC24, conserved site (conserved_site) [1371-1396]
- IPR011992: EF-hand domain pair (homologous_superfamily) [7-309]
- IPR002048: EF-hand domain (domain) [53-289]
- IPR035899: Dbl homology (DH) domain superfamily (homologous_superfamily) [1218-1440]
- IPR032140: Intersectin-1, AP2 binding region (domain) [803-917]
- IPR018247: EF-Hand 1, calcium-binding site (binding_site) [66-279]
- IPR051480: Endocytic & GEF Adapter (family) [975-1717]
- IPR011993: PH-like domain superfamily (homologous_superfamily) [1432-1579]
Interaction partners: - Cell division control protein 42 homolog
- Actin nucleation-promoting factor WASL
- F-BAR domain only protein 1
- Epidermal growth factor receptor substrate 15
- AP-2 complex subunit beta
- Epsin-2
- F-BAR domain only protein 2
- Stonin-2
- Dynamin-1
- Epsin-3
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0050793 (regulation of developmental process), GO:0050794 (regulation of cellular process), GO:0045927 (positive regulation of growth), GO:0051094 (positive regulation of developmental process), GO:0040008 (regulation of growth), GO:0048522 (positive regulation of cellular process), GO:0048639 (positive regulation of developmental growth), GO:0030307 (positive regulation of cell growth), GO:0051128 (regulation of cellular component organization), GO:0048638 (regulation of developmental growth), GO:0001558 (regulation of cell growth), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0022604 (regulation of cell morphogenesis), GO:1903859 (regulation of dendrite extension), GO:1903861 (positive regulation of dendrite extension)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0071944 (cell periphery), GO:0016020 (membrane), GO:0005886 (plasma membrane)