ID ITSN1_MOUSE Reviewed; 1714 AA. AC Q9Z0R4; F8VQE5; Q9R143; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2012, sequence version 2. DT 27-MAR-2024, entry version 210. DE RecName: Full=Intersectin-1 {ECO:0000305}; DE AltName: Full=EH and SH3 domains protein 1 {ECO:0000303|PubMed:10064583}; GN Name=Itsn1 {ECO:0000312|MGI:MGI:1338069}; GN Synonyms=Ese1 {ECO:0000303|PubMed:10064583}, Itsn; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH EPS15 RP AND DNM1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=10064583; DOI=10.1093/emboj/18.5.1159; RA Sengar A.S., Wang W., Bishay J., Cohen S., Egan S.E.; RT "The EH and SH3 domain Ese proteins regulate endocytosis by linking to RT dynamin and Eps15."; RL EMBO J. 18:1159-1171(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 966-1714, AND NUCLEOTIDE SEQUENCE RP [MRNA] OF 545-599 (ISOFORMS 1 AND 2). RC STRAIN=129/Ola; TISSUE=Spleen; RA Skripkina I.Y., Tsyba L.O., Anoprienko O.V., Slavov D., Tassone F., RA Rynditch A.V., Gardiner K.; RT "Mouse homologues of human chromosome 21 genes."; RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP INTERACTION WITH ARHGAP31. RX PubMed=11744688; DOI=10.1074/jbc.m105516200; RA Jenna S., Hussain N.K., Danek E.I., Triki I., Wasiak S., McPherson P.S., RA Lamarche-Vane N.; RT "The activity of the GTPase-activating protein CdGAP is regulated by the RT endocytic protein intersectin."; RL J. Biol. Chem. 277:6366-6373(2002). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic brain; RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200; RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; RT "Phosphoproteomic analysis of the developing mouse brain."; RL Mol. Cell. Proteomics 3:1093-1101(2004). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1130, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200; RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.; RT "Comprehensive identification of phosphorylation sites in postsynaptic RT density preparations."; RL Mol. Cell. Proteomics 5:914-922(2006). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CBL, AND TISSUE RP SPECIFICITY. RX PubMed=16914641; DOI=10.1124/mol.106.028274; RA Martin N.P., Mohney R.P., Dunn S., Das M., Scappini E., O'Bryan J.P.; RT "Intersectin regulates epidermal growth factor receptor endocytosis, RT ubiquitylation, and signaling."; RL Mol. Pharmacol. 70:1643-1653(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-334; SER-895; SER-897 AND RP THR-977, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [9] RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND ALTERNATIVE RP SPLICING. RX PubMed=18676989; DOI=10.1093/hmg/ddn224; RA Yu Y., Chu P.Y., Bowser D.N., Keating D.J., Dubach D., Harper I., RA Tkalcevic J., Finkelstein D.I., Pritchard M.A.; RT "Mice deficient for the chromosome 21 ortholog Itsn1 exhibit vesicle- RT trafficking abnormalities."; RL Hum. Mol. Genet. 17:3281-3290(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18630941; DOI=10.1021/pr800223m; RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.; RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity RT chromatography adsorbent for phosphoproteome analysis."; RL J. Proteome Res. 7:3957-3967(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203; SER-318; SER-334; RP SER-335; THR-890; SER-895; SER-897; SER-1130; THR-1137 AND SER-1638, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [13] RP INTERACTION WITH FCHO2. RX PubMed=20448150; DOI=10.1126/science.1188462; RA Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y., Mittal R., RA McMahon H.T.; RT "FCHo proteins are nucleators of clathrin-mediated endocytosis."; RL Science 328:1281-1284(2010). RN [14] RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND DISRUPTION RP PHENOTYPE. RX PubMed=23633571; DOI=10.1073/pnas.1219234110; RA Sakaba T., Kononenko N.L., Bacetic J., Pechstein A., Schmoranzer J., RA Yao L., Barth H., Shupliakov O., Kobler O., Aktories K., Haucke V.; RT "Fast neurotransmitter release regulated by the endocytic scaffold RT intersectin."; RL Proc. Natl. Acad. Sci. U.S.A. 110:8266-8271(2013). RN [15] RP INTERACTION WITH PRRT2. RX PubMed=26797119; DOI=10.1074/jbc.m115.683888; RA Rossi P., Sterlini B., Castroflorio E., Marte A., Onofri F., Valtorta F., RA Maragliano L., Corradi A., Benfenati F.; RT "A Novel Topology of Proline-rich Transmembrane Protein 2 (PRRT2): hints RT for an intracellular function at the synapse."; RL J. Biol. Chem. 291:6111-6123(2016). RN [16] RP INTERACTION WITH KPNA1. RX PubMed=29599122; DOI=10.1042/bcj20170897; RA Alvisi G., Paolini L., Contarini A., Zambarda C., Di Antonio V., RA Colosini A., Mercandelli N., Timmoneri M., Palu G., Caimi L., Ricotta D., RA Radeghieri A.; RT "Intersectin goes nuclear: secret life of an endocytic protein."; RL Biochem. J. 475:1455-1472(2018). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1151-1431, AND SH3 DOMAIN. RX PubMed=20585582; DOI=10.1371/journal.pone.0011291; RA Ahmad K.F., Lim W.A.; RT "The minimal autoinhibited unit of the guanine nucleotide exchange factor RT intersectin."; RL PLoS ONE 5:E11291-E11291(2010). CC -!- FUNCTION: Adapter protein that provides a link between the endocytic CC membrane traffic and the actin assembly machinery (PubMed:10064583). CC Acts as a guanine nucleotide exchange factor (GEF) for CDC42, and CC thereby stimulates actin nucleation mediated by WASL and the ARP2/3 CC complex (By similarity). Plays a role in the assembly and maturation of CC clathrin-coated vesicles (By similarity). Recruits FCHSD2 to clathrin- CC coated pits (By similarity). Involved in endocytosis of activated EGFR, CC and probably also other growth factor receptors (PubMed:16914641). CC Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin CC receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but CC not TFR may involve association with DAB2 (By similarity). Promotes CC ubiquitination and subsequent degradation of EGFR, and thereby CC contributes to the down-regulation of EGFR-dependent signaling pathways CC (PubMed:16914641). In chromaffin cells, required for normal exocytosis CC of catecholamines (PubMed:18676989). Required for rapid replenishment CC of release-ready synaptic vesicles at presynaptic active zones CC (PubMed:23633571). Inhibits ARHGAP31 activity toward RAC1 (By CC similarity). {ECO:0000250|UniProtKB:Q15811, CC ECO:0000250|UniProtKB:Q9WVE9, ECO:0000269|PubMed:10064583, CC ECO:0000269|PubMed:16914641, ECO:0000269|PubMed:18676989, CC ECO:0000269|PubMed:23633571}. CC -!- FUNCTION: [Isoform 1]: Plays a role in synaptic vesicle endocytosis in CC brain neurons. {ECO:0000269|PubMed:18676989}. CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00041}; CC -!- SUBUNIT: Interacts (via DH domain) with CDC42. Interacts (via SH3 CC domain 1) with WASL (By similarity). Interacts with dynamin, SNAP25 and CC SNAP23 (By similarity). Interacts with clathrin-associated proteins and CC other components of the endocytic machinery, such as SPIN90, EPS15, CC EPN1, EPN2, STON2, FCHO1, FCHO2 and DAB2 (PubMed:10064583, CC PubMed:20448150). Interacts (via SH3 domains) with REPS1 and SGIP1. CC Interacts with ARHGAP31 (PubMed:11744688). Interacts with ADAM15 (By CC similarity). Interacts with PRRT2 (PubMed:26797119). Interacts (via SH3 CC domain 4) with FCHSD2 (via SH3 domain 2). Interacts (via SH3 domain 1) CC with DENND2B (By similarity). Interacts (via SH3 domains) with CBL CC (PubMed:16914641). Isoform 2: Interacts with CBL and DNM1. Isoform 2: CC Interacts with LMNA (By similarity). Isoform 2: Interacts with importin CC subunit KPNA1; this is likely to mediate its import into the nucleus CC (PubMed:29599122). Interacts with DNM2 (By similarity). CC {ECO:0000250|UniProtKB:Q15811, ECO:0000250|UniProtKB:Q9WVE9, CC ECO:0000269|PubMed:10064583, ECO:0000269|PubMed:11744688, CC ECO:0000269|PubMed:16914641, ECO:0000269|PubMed:20448150, CC ECO:0000269|PubMed:26797119, ECO:0000269|PubMed:29599122}. CC -!- INTERACTION: CC Q9Z0R4; A6X8Z5: Arhgap31; NbExp=3; IntAct=EBI-645386, EBI-4325995; CC Q9Z0R4; Q8K382: Dennd1a; NbExp=3; IntAct=EBI-645386, EBI-7186684; CC Q9Z0R4-2; Q6P549: Inppl1; NbExp=2; IntAct=EBI-8052786, EBI-2642932; CC -!- SUBCELLULAR LOCATION: Endomembrane system CC {ECO:0000269|PubMed:16914641}. Synapse, synaptosome CC {ECO:0000250|UniProtKB:Q9WVE9}. Cell projection, lamellipodium CC {ECO:0000250|UniProtKB:Q15811}. Cell membrane CC {ECO:0000250|UniProtKB:Q15811}. Membrane, clathrin-coated pit CC {ECO:0000250|UniProtKB:Q15811}. Recycling endosome CC {ECO:0000250|UniProtKB:Q15811}. Endosome {ECO:0000269|PubMed:16914641}. CC Cytoplasmic vesicle {ECO:0000269|PubMed:16914641, CC ECO:0000269|PubMed:23633571}. Note=Colocalizes with SGIP1 at the plasma CC membrane in structures corresponding most probably to clathrin-coated CC pits. Colocalizes with RAB13 on cytoplasmic vesicles that are most CC likely recycling endosomes. {ECO:0000250|UniProtKB:Q15811}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000250|UniProtKB:Q15811}. Nucleus envelope CC {ECO:0000250|UniProtKB:Q15811}. Note=Shuttles between the cytoplasm and CC nucleus in an XPO1/CRM1-dependent manner. CC {ECO:0000250|UniProtKB:Q15811}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Additional isoforms seem to exist.; CC Name=1; Synonyms=Ese1L; CC IsoId=Q9Z0R4-1; Sequence=Displayed; CC Name=2; Synonyms=ITSN-s {ECO:0000250|UniProtKB:Q15811}; CC IsoId=Q9Z0R4-2; Sequence=VSP_004296; CC -!- TISSUE SPECIFICITY: Detected in brain, adrenal gland and heart CC (PubMed:16914641, PubMed:18676989). Detected in neurons at the calyx of CC Held (at protein level) (PubMed:23633571). Isoform 1: Primarily CC detected in brain neurons. Isoform 2: Primarily detected in glia (at CC protein level) (PubMed:18676989). Widely expressed. Expressed at high CC levels in brain, heart and skeletal muscle (PubMed:10064583). CC {ECO:0000269|PubMed:10064583, ECO:0000269|PubMed:16914641, CC ECO:0000269|PubMed:18676989, ECO:0000269|PubMed:23633571}. CC -!- DOMAIN: SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains, bind CC to dynamin (By similarity). SH3-1 and SH3-4 bind to ARHGAP31. CC {ECO:0000250}. CC -!- DOMAIN: The KLERQ domain binds to SNAP-25 and SNAP-23. {ECO:0000250}. CC -!- DOMAIN: In an autoinhibited form the SH3 domain 5 may bind CC intramolecularly to the DH domain, thus blocking the CDC42-binding CC site. {ECO:0000269|PubMed:20585582}. CC -!- DISRUPTION PHENOTYPE: No visible phenotype, except that about 13% of CC the pups do not thrive. Mice are born at the expected Mendelian rate CC (PubMed:18676989). Mutant mice display no obvious defects in synaptic CC responses to single stimuli at the calyx of Held. Repetitive CC stimulation gives rise to decreased synaptic responses, due to CC perturbation of the replenishment of release-ready synaptic vesicles CC (PubMed:23633571). {ECO:0000269|PubMed:18676989, CC ECO:0000269|PubMed:23633571}. CC -!- MISCELLANEOUS: Overexpression results in the inhibition of the CC transferrin uptake and the blockage of the clathrin-mediated CC endocytosis. {ECO:0000269|PubMed:10064583}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF132481; AAD19749.1; -; mRNA. DR EMBL; AF132478; AAD19746.1; -; mRNA. DR EMBL; AC126053; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC131691; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC134837; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF169621; AAD48848.1; -; mRNA. DR EMBL; AF356517; AAK40228.1; -; Genomic_DNA. DR CCDS; CCDS37402.1; -. [Q9Z0R4-1] DR CCDS; CCDS49913.1; -. [Q9Z0R4-2] DR RefSeq; NP_001103745.1; NM_001110275.1. [Q9Z0R4-2] DR RefSeq; NP_034717.2; NM_010587.2. [Q9Z0R4-1] DR PDB; 3HS8; X-ray; 1.90 A; P=840-851. DR PDB; 3JV3; X-ray; 2.40 A; A/B=1151-1431. DR PDBsum; 3HS8; -. DR PDBsum; 3JV3; -. DR AlphaFoldDB; Q9Z0R4; -. DR SMR; Q9Z0R4; -. DR BioGRID; 200851; 15. DR IntAct; Q9Z0R4; 18. DR MINT; Q9Z0R4; -. DR STRING; 10090.ENSMUSP00000109635; -. DR GlyGen; Q9Z0R4; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q9Z0R4; -. DR PhosphoSitePlus; Q9Z0R4; -. DR SwissPalm; Q9Z0R4; -. DR EPD; Q9Z0R4; -. DR jPOST; Q9Z0R4; -. DR MaxQB; Q9Z0R4; -. DR PaxDb; 10090-ENSMUSP00000109635; -. DR PeptideAtlas; Q9Z0R4; -. DR ProteomicsDB; 269017; -. [Q9Z0R4-1] DR ProteomicsDB; 269018; -. [Q9Z0R4-2] DR Pumba; Q9Z0R4; -. DR Antibodypedia; 7532; 106 antibodies from 19 providers. DR DNASU; 16443; -. DR Ensembl; ENSMUST00000056482.14; ENSMUSP00000056011.8; ENSMUSG00000022957.21. [Q9Z0R4-2] DR Ensembl; ENSMUST00000114002.9; ENSMUSP00000109635.3; ENSMUSG00000022957.21. [Q9Z0R4-1] DR GeneID; 16443; -. DR KEGG; mmu:16443; -. DR UCSC; uc007zyi.2; mouse. [Q9Z0R4-1] DR AGR; MGI:1338069; -. DR CTD; 6453; -. DR MGI; MGI:1338069; Itsn1. DR VEuPathDB; HostDB:ENSMUSG00000022957; -. DR eggNOG; KOG1029; Eukaryota. DR eggNOG; KOG4305; Eukaryota. DR GeneTree; ENSGT00940000157065; -. DR HOGENOM; CLU_002819_2_0_1; -. DR InParanoid; Q9Z0R4; -. DR OMA; XCSDLHL; -. DR OrthoDB; 2910300at2759; -. DR TreeFam; TF324293; -. DR Reactome; R-MMU-193648; NRAGE signals death through JNK. DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling. DR Reactome; R-MMU-416482; G alpha (12/13) signalling events. DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis. DR Reactome; R-MMU-9013148; CDC42 GTPase cycle. DR Reactome; R-MMU-9013406; RHOQ GTPase cycle. DR Reactome; R-MMU-9013408; RHOG GTPase cycle. DR BioGRID-ORCS; 16443; 1 hit in 78 CRISPR screens. DR ChiTaRS; Itsn1; mouse. DR EvolutionaryTrace; Q9Z0R4; -. DR PRO; PR:Q9Z0R4; -. DR Proteomes; UP000000589; Chromosome 16. DR RNAct; Q9Z0R4; Protein. DR Bgee; ENSMUSG00000022957; Expressed in floor plate of midbrain and 277 other cell types or tissues. DR ExpressionAtlas; Q9Z0R4; baseline and differential. DR GO; GO:0097440; C:apical dendrite; ISO:MGI. DR GO; GO:0044305; C:calyx of Held; IDA:SynGO. DR GO; GO:0005905; C:clathrin-coated pit; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043197; C:dendritic spine; ISO:MGI. DR GO; GO:0030139; C:endocytic vesicle; IDA:MGI. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0097708; C:intracellular vesicle; ISO:MGI. DR GO; GO:0030027; C:lamellipodium; IDA:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0098871; C:postsynaptic actin cytoskeleton; ISO:MGI. DR GO; GO:0098833; C:presynaptic endocytic zone; IDA:SynGO. DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central. DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:InterPro. DR GO; GO:0019209; F:kinase activator activity; IDA:MGI. DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI. DR GO; GO:0070064; F:proline-rich region binding; ISO:MGI. DR GO; GO:0150007; P:clathrin-dependent synaptic vesicle endocytosis; IBA:GO_Central. DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central. DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI. DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI. DR GO; GO:2001288; P:positive regulation of caveolin-mediated endocytosis; ISO:MGI. DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISO:MGI. DR GO; GO:0060124; P:positive regulation of growth hormone secretion; ISO:MGI. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:MGI. DR GO; GO:0008104; P:protein localization; ISO:MGI. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:1905274; P:regulation of modification of postsynaptic actin cytoskeleton; ISO:MGI. DR GO; GO:0099175; P:regulation of postsynapse organization; ISO:MGI. DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:MGI. DR GO; GO:0048488; P:synaptic vesicle endocytosis; IDA:SynGO. DR CDD; cd08375; C2_Intersectin; 1. DR CDD; cd00052; EH; 2. DR CDD; cd13264; PH_ITSN; 1. DR CDD; cd00160; RhoGEF; 1. DR CDD; cd11987; SH3_Intersectin1_1; 1. DR CDD; cd11989; SH3_Intersectin1_2; 1. DR CDD; cd11991; SH3_Intersectin1_3; 1. DR CDD; cd11993; SH3_Intersectin1_4; 1. DR CDD; cd11995; SH3_Intersectin1_5; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.20.900.10; Dbl homology (DH) domain; 1. DR Gene3D; 1.10.238.10; EF-hand; 2. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 2.30.30.40; SH3 Domains; 5. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR035899; DBL_dom_sf. DR InterPro; IPR000219; DH-domain. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR000261; EH_dom. DR InterPro; IPR001331; GDS_CDC24_CS. DR InterPro; IPR032140; INTAP. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR46006:SF9; INTERSECTIN-2 ISOFORM X1; 1. DR PANTHER; PTHR46006; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR AT 64C, ISOFORM A; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF12763; EF-hand_4; 2. DR Pfam; PF16617; INTAP; 1. DR Pfam; PF16652; PH_13; 1. DR Pfam; PF00621; RhoGEF; 1. DR Pfam; PF00018; SH3_1; 3. DR Pfam; PF07653; SH3_2; 1. DR Pfam; PF14604; SH3_9; 1. DR PRINTS; PR00452; SH3DOMAIN. DR SMART; SM00239; C2; 1. DR SMART; SM00054; EFh; 2. DR SMART; SM00027; EH; 2. DR SMART; SM00233; PH; 1. DR SMART; SM00325; RhoGEF; 1. DR SMART; SM00326; SH3; 5. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF48065; DBL homology domain (DH-domain); 1. DR SUPFAM; SSF47473; EF-hand; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF50044; SH3-domain; 5. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS00741; DH_1; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS00018; EF_HAND_1; 2. DR PROSITE; PS50222; EF_HAND_2; 2. DR PROSITE; PS50031; EH; 2. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50002; SH3; 5. DR Genevisible; Q9Z0R4; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cell membrane; KW Cell projection; Coated pit; Coiled coil; Cytoplasm; Cytoplasmic vesicle; KW Endocytosis; Endosome; Exocytosis; Membrane; Metal-binding; Nucleus; KW Phosphoprotein; Protein transport; Reference proteome; Repeat; SH3 domain; KW Synapse; Synaptosome; Transport. FT CHAIN 1..1714 FT /note="Intersectin-1" FT /id="PRO_0000080958" FT DOMAIN 21..109 FT /note="EH 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00077" FT DOMAIN 53..88 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 221..310 FT /note="EH 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00077" FT DOMAIN 254..289 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 738..799 FT /note="SH3 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 906..964 FT /note="SH3 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 995..1053 FT /note="SH3 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 1067..1131 FT /note="SH3 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 1148..1207 FT /note="SH3 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 1230..1416 FT /note="DH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062" FT DOMAIN 1455..1564 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 1572..1688 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 310..356 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 326..702 FT /note="KLERQ" FT REGION 614..706 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 827..863 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1067..1131 FT /note="Required for interaction with FCHSD2" FT /evidence="ECO:0000250|UniProtKB:Q15811" FT COILED 354..658 FT /evidence="ECO:0000255" FT MOTIF 1097..1120 FT /note="Bipartite nuclear localization signal; in isoform 2" FT /evidence="ECO:0000250|UniProtKB:Q15811" FT COMPBIAS 314..329 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 330..356 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 625..706 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 830..863 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 66 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 68 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 70 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 72 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 77 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 267 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 269 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 271 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 273 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 278 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 1660 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1663 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1666 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT MOD_RES 203 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15345747, FT ECO:0007744|PubMed:21183079" FT MOD_RES 318 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 334 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 335 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 685 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9WVE9" FT MOD_RES 890 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 894 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15811" FT MOD_RES 895 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 897 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 971 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9WVE9" FT MOD_RES 977 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17242355" FT MOD_RES 979 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15811" FT MOD_RES 988 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15811" FT MOD_RES 1130 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16452087, FT ECO:0007744|PubMed:21183079" FT MOD_RES 1137 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1638 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT VAR_SEQ 1214..1714 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_004296" FT CONFLICT 179 FT /note="L -> W (in Ref. 1; AAD19749/AAD19746)" FT /evidence="ECO:0000305" FT CONFLICT 402 FT /note="R -> A (in Ref. 1; AAD19749/AAD19746)" FT /evidence="ECO:0000305" FT STRAND 1151..1157 FT /evidence="ECO:0007829|PDB:3JV3" FT STRAND 1174..1179 FT /evidence="ECO:0007829|PDB:3JV3" FT STRAND 1185..1190 FT /evidence="ECO:0007829|PDB:3JV3" FT STRAND 1193..1198 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1199..1201 FT /evidence="ECO:0007829|PDB:3JV3" FT STRAND 1202..1204 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1205..1207 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1210..1214 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1221..1223 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1226..1255 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1258..1261 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1268..1275 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1278..1299 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1309..1315 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1316..1320 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1321..1342 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1344..1353 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1357..1359 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1364..1367 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1370..1386 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1396..1422 FT /evidence="ECO:0007829|PDB:3JV3" FT HELIX 1423..1425 FT /evidence="ECO:0007829|PDB:3JV3" SQ SEQUENCE 1714 AA; 194297 MW; BCF5038160E8208E CRC64; MAQFPTPFGG SLDVWAITVE ERAKHDQQFL SLKPIAGFIT GDQARNFFFQ SGLPQPVLAQ IWALADMNND GRMDQVEFSI AMKLIKLKLQ GYQLPSTLPP VMKQQPVAIS SAPAFGIGGI ASMPPLTAVA PVPMGSIPVV GMSPPLVSSV PPAAVPPLAN GAPPVIQPLP AFAHPAATLP KSSSFSRSGP GSQLNTKLQK AQSFDVASAP PAAEWAVPQS SRLKYRQLFN SHDKTMSGHL TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP PEYIPPSFRR VRSGSGMSVI SSSSVDQRLP EEPSSEDEQQ PEKKLPVTFE DKKRENFERG SVELEKRRQA LLEQQRKEQE RLAQLERAEQ ERKERERQEQ ERKRQLELEK QLEKQRELER QREEERRKEI ERREAAKREL ERQRQLEWER NRRQELLNQR NKEQEGTVVL KARRKTLEFE LEALNDKKHQ LEGKLQDIRC RLATQRQEIE STNKSRELRI AEITHLQQQL QESQQMLGRL IPEKQILSDQ LKQVQQNSLH RDSLLTLKRA LEAKELARQQ LREQLDEVER ETRSKLQEID VFNNQLKELR EIHSKQQLQK QRSLEAARLK QKEQERKSLE LEKQKEDAQR RVQERDKQWL EHVQQEEQPR PRKPHEEDRL KREDSVRKKE AEERAKPEMQ DKQSRLFHPH QEPAKLATQA PWSTTEKGPL TISAQESVKV VYYRALYPFE SRSHDEITIQ PGDIVMVDES QTGEPGWLGG ELKGKTGWFP ANYAEKIPEN EVPTPAKPVT DLTSAPAPKL ALRETPAPLP VTSSEPSTTP NNWADFSSTW PSSSNEKPET DNWDTWAAQP SLTVPSAGQL RQRSAFTPAT ATGSSPSPVL GQGEKVEGLQ AQALYPWRAK KDNHLNFNKS DVITVLEQQD MWWFGEVQGQ KGWFPKSYVK LISGPVRKST SIDTGPTESP ASLKRVASPA AKPAIPGEEF IAMYTYESSE QGDLTFQQGD VIVVTKKDGD WWTGTVGDKS GVFPSNYVRL KDSEGSGTAG KTGSLGKKPE IAQVIASYAA TGPEQLTLAP GQLILIRKKN PGGWWEGELQ ARGKKRQIGW FPANYVKLLS PGTSKITPTE LPKTAVQPAV CQVIGMYDYT AQNDDELAFS KGQIINVLNK EDPDWWKGEV SGQVGLFPSN YVKLTTDMDP SQQWCSDLHL LDMLTPTERK RQGYIHELIV TEENYVNDLQ LVTEIFQKPL TESELLTEKE VAMIFVNWKE LIMCNIKLLK ALRVRKKMSG EKMPVKMIGD ILSAQLPHMQ PYIRFCSCQL NGAALIQQKT DEAPDFKEFV KRLAMDPRCK GMPLSSFILK PMQRVTRYPL IIKNILENTP ENHPDHSHLK HALEKAEELC SQVNEGVREK ENSDRLEWIQ AHVQCEGLSE QLVFNSVTNC LGPRKFLHSG KLYKAKSNKE LYGFLFNDFL LLTQITKPLG SSGTDKVFSP KSNLQYKMYK TPIFLNEVLV KLPTDPSGDE PIFHISHIDR VYTLRAESIN ERTAWVQKIK AASELYIETE KKKREKAYLV RSQRATGIGR LMVNVVEGIE LKPCRSHGKS NPYCEVTMGS QCHITKTIQD TLNPKWNSNC QFFIRDLEQE VLCITVFERD QFSPDDFLGR TEIRVADIKK DQGSKGPVTK CLLLHEVPTG EIVVRLDLQL FDEP //