Protein: Intersectin-1 (EH and SH3 domains protein 1) (Q9Z0R4)
Organism: Mus musculus (Mouse)
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 (By similarity). Recruits FCHSD2 to clathrin-coated pits (By similarity). Involved in endocytosis of activated EGFR, and probably also other growth factor receptors. 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. 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:0000269|PubMed:16914641}. Synapse, synaptosome {ECO:0000250|UniProtKB:Q9WVE9}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:Q15811}. Cell membrane {ECO:0000250|UniProtKB:Q15811}. Membrane, clathrin-coated pit {ECO:0000250|UniProtKB:Q15811}. Recycling endosome {ECO:0000250|UniProtKB:Q15811}. Endosome {ECO:0000269|PubMed:16914641}. Cytoplasmic vesicle {ECO:0000269|PubMed:16914641, ECO:0000269|PubMed:23633571}. 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}.
Sequence: MAQFPTPFGGSLDVWAITVEERAKHDQQFLSLKPIAGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQVEFSIAMKLIKLKLQGYQLPSTLPPVMKQQPVAISSAPAFGIGGIASMPPLTAVAPVPMGSIPVVGMSPPLVSSVPPAAVPPLANGAPPVIQPLPAFAHPAATLPKSSSFSRSGPGSQLNTKLQKAQSFDVASAPPAAEWAVPQSSRLKYRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMSGQPLPPVLPPEYIPPSFRRVRSGSGMSVISSSSVDQRLPEEPSSEDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSRLFHPHQEPAKLATQAPWSTTEKGPLTISAQESVKVVYYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEKIPENEVPTPAKPVTDLTSAPAPKLALRETPAPLPVTSSEPSTTPNNWADFSSTWPSSSNEKPETDNWDTWAAQPSLTVPSAGQLRQRSAFTPATATGSSPSPVLGQGEKVEGLQAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQGQKGWFPKSYVKLISGPVRKSTSIDTGPTESPASLKRVASPAAKPAIPGEEFIAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTGTVGDKSGVFPSNYVRLKDSEGSGTAGKTGSLGKKPEIAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLLSPGTSKITPTELPKTAVQPAVCQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKLTTDMDPSQQWCSDLHLLDMLTPTERKRQGYIHELIVTEENYVNDLQLVTEIFQKPLTESELLTEKEVAMIFVNWKELIMCNIKLLKALRVRKKMSGEKMPVKMIGDILSAQLPHMQPYIRFCSCQLNGAALIQQKTDEAPDFKEFVKRLAMDPRCKGMPLSSFILKPMQRVTRYPLIIKNILENTPENHPDHSHLKHALEKAEELCSQVNEGVREKENSDRLEWIQAHVQCEGLSEQLVFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQITKPLGSSGTDKVFSPKSNLQYKMYKTPIFLNEVLVKLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKKKREKAYLVRSQRATGIGRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDFLGRTEIRVADIKKDQGSKGPVTKCLLLHEVPTGEIVVRLDLQLFDEP
InterPro domains: - IPR000219: Dbl homology domain (domain) [1230-1416]
- IPR035892: C2 domain superfamily (homologous_superfamily) [1587-1712]
- IPR001849: Pleckstrin homology domain (domain) [1433-1586]
- IPR000261: EH domain (domain) [14-310]
- IPR036028: SH3-like domain superfamily (homologous_superfamily) [724-1216]
- IPR000008: C2 domain (domain) [1572-1688]
- IPR001452: SH3 domain (domain) [738-1207]
- IPR001331: Guanine-nucleotide dissociation stimulator, CDC24, conserved site (conserved_site) [1364-1389]
- IPR011992: EF-hand domain pair (homologous_superfamily) [7-309]
- IPR002048: EF-hand domain (domain) [53-289]
- IPR035899: Dbl homology (DH) domain superfamily (homologous_superfamily) [1211-1433]
- IPR032140: Intersectin-1, AP2 binding region (domain) [796-910]
- IPR018247: EF-Hand 1, calcium-binding site (binding_site) [66-279]
- IPR051480: Endocytic & GEF Adapter (family) [1000-1710]
- IPR011993: PH-like domain superfamily (homologous_superfamily) [1425-1572]
Interaction partners: - Cell division control protein 42 homolog
- F-BAR domain only protein 1
- Actin nucleation-promoting factor WASL
- Epidermal growth factor receptor substrate 15
- Ephrin type-B receptor 2
- Epsin-1
- Stonin-2
- Synaptojanin-1
- AP-2 complex subunit alpha-2
- Dynamin-1
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:0032502 (developmental process), GO:0009987 (cellular process), GO:0032501 (multicellular organismal process), GO:0048869 (cellular developmental process), GO:0050793 (regulation of developmental process), GO:0048856 (anatomical structure development), GO:0023056 (positive regulation of signaling), GO:0007275 (multicellular organism development), GO:0048870 (cell motility), GO:0048584 (positive regulation of response to stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0023051 (regulation of signaling), GO:0048522 (positive regulation of cellular process), GO:0009967 (positive regulation of signal transduction), GO:0030154 (cell differentiation), GO:0010646 (regulation of cell communication), GO:0048731 (system development), GO:0009966 (regulation of signal transduction), GO:0045595 (regulation of cell differentiation), GO:0010647 (positive regulation of cell communication), GO:0016477 (cell migration), GO:0022008 (neurogenesis), GO:0007399 (nervous system development), GO:0001764 (neuron migration), GO:1902533 (positive regulation of intracellular signal transduction), GO:1902531 (regulation of intracellular signal transduction), GO:0043408 (regulation of MAPK cascade), GO:0043410 (positive regulation of MAPK cascade), GO:0048699 (generation of neurons), GO:0070374 (positive regulation of ERK1 and ERK2 cascade), GO:0070372 (regulation of ERK1 and ERK2 cascade)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0045177 (apical part of cell), GO:0016020 (membrane), GO:0030054 (cell junction), GO:0098793 (presynapse), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0042734 (presynaptic membrane), GO:0098590 (plasma membrane region), GO:0045179 (apical cortex), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0005938 (cell cortex), GO:0099568 (cytoplasmic region), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0016324 (apical plasma membrane), GO:0043228 (non-membrane-bounded organelle), GO:0030863 (cortical cytoskeleton), GO:0043231 (intracellular membrane-bounded organelle), GO:0099738 (cell cortex region), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0005856 (cytoskeleton), GO:0030864 (cortical actin cytoskeleton), GO:0005634 (nucleus), GO:0015629 (actin cytoskeleton)