ITSN1_MOUSE
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 03-AUG-2022, entry version 201.
DE RecName: Full=Intersectin-1;
DE AltName: Full=EH and SH3 domains protein 1 {ECO:0000303|PubMed:10064583};
GN Name=Itsn1; 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, Pancreas,
RC 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 guanine nucleotide exchange factor (GEF) for CDC42, and thereby
CC stimulates actin nucleation mediated by WASL and the ARP2/3 complex (By
CC similarity). Plays a role in the assembly and maturation of clathrin-
CC coated vesicles (By similarity). Recruits FCHSD2 to clathrin-coated
CC pits (By similarity). Involved in endocytosis of activated EGFR, and
CC probably also other growth factor receptors (PubMed:16914641). Involved
CC in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor
CC (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may
CC involve association with DAB2 (By similarity). Promotes ubiquitination
CC and subsequent degradation of EGFR, and thereby contributes to the
CC down-regulation of EGFR-dependent signaling pathways (PubMed:16914641).
CC In chromaffin cells, required for normal exocytosis of catecholamines
CC (PubMed:18676989). Required for rapid replenishment of release-ready
CC synaptic vesicles at presynaptic active zones (PubMed:23633571).
CC Inhibits ARHGAP31 activity toward RAC1 (By similarity).
CC {ECO:0000250|UniProtKB:Q15811, ECO:0000250|UniProtKB:Q9WVE9,
CC ECO:0000269|PubMed:10064583, ECO:0000269|PubMed:16914641,
CC ECO:0000269|PubMed:18676989, 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;
CC Evidence={ECO:0000255|PROSITE-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). {ECO:0000250|UniProtKB:Q15811,
CC ECO:0000250|UniProtKB:Q9WVE9, ECO:0000269|PubMed:10064583,
CC ECO:0000269|PubMed:11744688, ECO:0000269|PubMed:16914641,
CC ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:26797119,
CC 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}.
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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; 14.
DR IntAct; Q9Z0R4; 16.
DR MINT; Q9Z0R4; -.
DR STRING; 10090.ENSMUSP00000109635; -.
DR iPTMnet; Q9Z0R4; -.
DR PhosphoSitePlus; Q9Z0R4; -.
DR EPD; Q9Z0R4; -.
DR jPOST; Q9Z0R4; -.
DR MaxQB; Q9Z0R4; -.
DR PaxDb; Q9Z0R4; -.
DR PeptideAtlas; Q9Z0R4; -.
DR PRIDE; Q9Z0R4; -.
DR ProteomicsDB; 269017; -. [Q9Z0R4-1]
DR ProteomicsDB; 269018; -. [Q9Z0R4-2]
DR Antibodypedia; 7532; 89 antibodies from 18 providers.
DR DNASU; 16443; -.
DR Ensembl; ENSMUST00000056482; ENSMUSP00000056011; ENSMUSG00000022957. [Q9Z0R4-2]
DR Ensembl; ENSMUST00000114002; ENSMUSP00000109635; ENSMUSG00000022957. [Q9Z0R4-1]
DR GeneID; 16443; -.
DR KEGG; mmu:16443; -.
DR UCSC; uc007zyi.2; mouse. [Q9Z0R4-1]
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; WEGELQX; -.
DR OrthoDB; 807060at2759; -.
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 73 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 273 other tissues.
DR ExpressionAtlas; Q9Z0R4; baseline and differential.
DR Genevisible; Q9Z0R4; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; ISO:MGI.
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:0006897; P: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 protein kinase B signaling; 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:0007264; P:small GTPase mediated signal transduction; IDA:MGI.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IDA:SynGO.
DR CDD; cd00052; EH; 2.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
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 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; SSF47473; SSF47473; 2.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF50044; SSF50044; 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.
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
