ID ITSN1_HUMAN Reviewed; 1721 AA. AC Q15811; A7Y322; A8CTX8; A8CTY3; A8CTY7; A8D7D0; A8DCP3; B4DTM2; E7ERJ1; AC E9PE44; E9PG01; E9PHV2; O95216; Q0PW94; Q0PW95; Q0PW97; Q14BD3; Q1ED40; AC Q20BK3; Q9UET5; Q9UK60; Q9UNK1; Q9UNK2; Q9UQ92; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 27-MAR-2024, entry version 232. DE RecName: Full=Intersectin-1 {ECO:0000305}; DE AltName: Full=SH3 domain-containing protein 1A {ECO:0000303|PubMed:9465890}; DE AltName: Full=SH3P17; GN Name=ITSN1 {ECO:0000312|HGNC:HGNC:6183}; GN Synonyms=ITSN {ECO:0000303|PubMed:10482960, GN ECO:0000303|PubMed:9799604}, SH3D1A {ECO:0000303|PubMed:9465890}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANT RP ASN-1137, AND TISSUE SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=9799604; DOI=10.1006/geno.1998.5521; RA Guipponi M., Scott H.S., Chen H., Schebesta A., Rossier C., RA Antonarakis S.E.; RT "Two isoforms of a human intersectin (ITSN) protein are produced by brain- RT specific alternative splicing in a stop codon."; RL Genomics 53:369-376(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RX PubMed=10482960; DOI=10.1038/sj.ejhg.5200356; RA Pucharcos C., Fuentes J.-J., Casas C., de la Luna S., Alcantara S., RA Arbones M.L., Soriano E., Estivill X., Pritchard M.; RT "Alu-splice cloning of human intersectin (ITSN), a putative multivalent RT binding protein expressed in proliferating and differentiating neurons and RT overexpressed in Down syndrome."; RL Eur. J. Hum. Genet. 7:704-712(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 6; 7; 8; 9; 10; 11 AND 12), VARIANT RP ASN-1137, AND ALTERNATIVE SPLICING. RC TISSUE=Brain, and Lung; RX PubMed=19777371; DOI=10.1007/s11033-009-9824-8; RA Kropyvko S., Gerasymchuk D., Skrypkina I., Dergai M., Dergai O., RA Nikolaienko O., Rynditch A., Tsyba L.; RT "Structural diversity and differential expression of novel human RT intersectin 1 isoforms."; RL Mol. Biol. Rep. 37:2789-2796(2010). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), ALTERNATIVE SPLICING, SUBCELLULAR RP LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH CBL AND DNM1. RC TISSUE=Kidney; RX PubMed=21712076; DOI=10.1016/j.gene.2011.06.021; RA Dergai M., Skrypkina I., Dergai O., Tsyba L., Novokhatska O., Filonenko V., RA Drobot L., Rynditch A.; RT "Identification and characterization of a novel mammalian isoform of the RT endocytic adaptor ITSN1."; RL Gene 485:120-129(2011). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Embryonic stem cell; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 620-1721 (ISOFORM 3). RC TISSUE=Bone marrow; RX PubMed=9630982; DOI=10.1038/nbt0696-741; RA Sparks A.B., Hoffman N.G., McConnell S.J., Fowlkes D.M., Kay B.K.; RT "Cloning of ligand targets: systematic isolation of SH3 domain-containing RT proteins."; RL Nat. Biotechnol. 14:741-744(1996). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 963-1721 (ISOFORM 3). RC TISSUE=Brain; RA Tsyba L.O., Kvasha S.M., Skripkina I.Y., Anoprienko O.V., Slavov D., RA Tassone F., Rynditch A.V., Gardiner K.; RT "Mouse homologs of human chromosome 21 genes."; RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases. RN [10] RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RC TISSUE=Brain, and Fetal liver; RX PubMed=11690630; DOI=10.1016/s0167-4781(01)00276-7; RA Pucharcos C., Casas C., Nadal M., Estivill X., de la Luna S.; RT "The human intersectin genes and their spliced variants are differentially RT expressed."; RL Biochim. Biophys. Acta 1521:1-11(2001). RN [11] RP GENE MAPPING. RX PubMed=9465890; DOI=10.1159/000134659; RA Chen H., Antonarakis S.E.; RT "The SH3D1A gene maps to human chromosome 21q22.1-->q22.2."; RL Cytogenet. Cell Genet. 78:213-215(1997). RN [12] RP FUNCTION, AND INTERACTION WITH CDC42 AND WASL. RX PubMed=11584276; DOI=10.1038/ncb1001-927; RA Hussain N.K., Jenna S., Glogauer M., Quinn C.C., Wasiak S., Guipponi M., RA Antonarakis S.E., Kay B.K., Stossel T.P., Lamarche-Vane N., McPherson P.S.; RT "Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N- RT WASP."; RL Nat. Cell Biol. 3:927-932(2001). RN [13] RP FUNCTION, INTERACTION WITH ARHGAP31, AND SUBCELLULAR LOCATION. 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-902 AND SER-904, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [16] RP INTERACTION WITH ADAM15. RX PubMed=19718658; DOI=10.1002/jcb.22317; RA Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.; RT "Alternative splicing of ADAM15 regulates its interactions with cellular RT SH3 proteins."; RL J. Cell. Biochem. 108:877-885(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [18] RP INTERACTION WITH REPS1 AND SGIP1, AND SUBCELLULAR LOCATION. RX PubMed=20946875; DOI=10.1016/j.bbrc.2010.10.045; RA Dergai O., Novokhatska O., Dergai M., Skrypkina I., Tsyba L., Moreau J., RA Rynditch A.; RT "Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated RT pits."; RL Biochem. Biophys. Res. Commun. 402:408-413(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [20] 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 [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [22] RP FUNCTION, AND INTERACTION WITH DAB2. RX PubMed=22648170; DOI=10.1091/mbc.e11-12-1007; RA Teckchandani A., Mulkearns E.E., Randolph T.W., Toida N., Cooper J.A.; RT "The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate RT integrin beta1 endocytosis."; RL Mol. Biol. Cell 23:2905-2916(2012). RN [23] RP INTERACTION WITH FCHO1. RX PubMed=22484487; DOI=10.1038/ncb2473; RA Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B., RA Tsang M., Traub L.M.; RT "Distinct and separable activities of the endocytic clathrin-coat RT components Fcho1/2 and AP-2 in developmental patterning."; RL Nat. Cell Biol. 14:488-501(2012). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203; SER-902; SER-904; RP SER-986 AND SER-1137, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-901; SER-902; SER-904; RP SER-995 AND THR-1144, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP INTERACTION WITH VACCINIA VIRUS PROTEIN A36. RX PubMed=27670116; DOI=10.1038/nmicrobiol.2016.141; RA Snetkov X., Weisswange I., Pfanzelter J., Humphries A.C., Way M.; RT "NPF motifs in the vaccinia virus protein A36 recruit intersectin-1 to RT promote Cdc42:N-WASP-mediated viral release from infected cells."; RL Nat. Microbiol. 1:16141-16141(2016). RN [27] RP INTERACTION WITH DENND2B, AND SUBCELLULAR LOCATION. RX PubMed=29030480; DOI=10.15252/embr.201744034; RA Ioannou M.S., Kulasekaran G., Fotouhi M., Morein J.J., Han C., Tse S., RA Nossova N., Han T., Mannard E., McPherson P.S.; RT "Intersectin-s interaction with DENND2B facilitates recycling of epidermal RT growth factor receptor."; RL EMBO Rep. 18:2119-2130(2017). RN [28] RP INTERACTION WITH KPNA1 AND LMNA (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM RP 2), AND NUCLEAR LOCALIZATION SIGNAL (ISOFORM 2). 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 [29] RP INTERACTION WITH DNM2. RX PubMed=32315611; DOI=10.1016/j.devcel.2020.03.018; RA Puri C., Manni M.M., Vicinanza M., Hilcenko C., Zhu Y., Runwal G., RA Stamatakou E., Menzies F.M., Mamchaoui K., Bitoun M., Rubinsztein D.C.; RT "A DNM2 Centronuclear Myopathy Mutation Reveals a Link between Recycling RT Endosome Scission and Autophagy."; RL Dev. Cell 53:154.e6-168.e6(2020). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1229-1581 IN COMPLEX WITH CDC42, RP AND MUTAGENESIS OF MET-1369 AND LEU-1376. RX PubMed=12006984; DOI=10.1038/nsb796; RA Snyder J.T., Worthylake D.K., Rossman K.L., Betts L., Pruitt W.M., RA Siderovski D.P., Der C.J., Sondek J.; RT "Structural basis for the selective activation of Rho GTPases by Dbl RT exchange factors."; RL Nat. Struct. Biol. 9:468-475(2002). RN [31] {ECO:0007744|PDB:6GBU} RP X-RAY CRYSTALLOGRAPHY (3.44 ANGSTROMS) OF 1074-1138 IN COMPLEX WITH FCHSD2, RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ILE-1078 AND ARG-1119. RX PubMed=29887380; DOI=10.1016/j.cell.2018.05.020; RA Almeida-Souza L., Frank R.A.W., Garcia-Nafria J., Colussi A., RA Gunawardana N., Johnson C.M., Yu M., Howard G., Andrews B., Vallis Y., RA McMahon H.T.; RT "A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin- RT Coated Pits."; RL Cell 174:325-337(2018). CC -!- FUNCTION: Adapter protein that provides a link between the endocytic CC membrane traffic and the actin assembly machinery (PubMed:11584276, CC PubMed:29887380). Acts as a guanine nucleotide exchange factor (GEF) CC for CDC42, and thereby stimulates actin nucleation mediated by WASL and CC the ARP2/3 complex (PubMed:11584276). Plays a role in the assembly and CC maturation of clathrin-coated vesicles (By similarity). Recruits FCHSD2 CC to clathrin-coated pits (PubMed:29887380). Involved in endocytosis of CC activated EGFR, and probably also other growth factor receptors (By CC similarity). Involved in endocytosis of integrin beta-1 (ITGB1) and CC transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent CC cargo but not TFR may involve association with DAB2 (PubMed:22648170). CC Promotes ubiquitination and subsequent degradation of EGFR, and thereby CC contributes to the down-regulation of EGFR-dependent signaling CC pathways. In chromaffin cells, required for normal exocytosis of CC catecholamines. Required for rapid replenishment of release-ready CC synaptic vesicles at presynaptic active zones (By similarity). Inhibits CC ARHGAP31 activity toward RAC1 (PubMed:11744688). CC {ECO:0000250|UniProtKB:Q9WVE9, ECO:0000250|UniProtKB:Q9Z0R4, CC ECO:0000269|PubMed:11584276, ECO:0000269|PubMed:11744688, CC ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:29887380}. CC -!- FUNCTION: [Isoform 1]: Plays a role in synaptic vesicle endocytosis in CC brain neurons. {ECO:0000250|UniProtKB:Q9Z0R4}. 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 (PubMed:11584276, CC PubMed:12006984). Interacts (via SH3 domain 1) with WASL CC (PubMed:11584276). Interacts with dynamin, SNAP25 and SNAP23 (By CC similarity). Interacts with clathrin-associated proteins and other CC components of the endocytic machinery, such as SPIN90, EPS15, EPN1, CC EPN2, STON2, FCHO1, FCHO2 and DAB2 (PubMed:20448150, PubMed:22484487, CC PubMed:22648170). Interacts (via SH3 domains) with REPS1 and SGIP1 CC (PubMed:20946875). Interacts with ARHGAP31 (PubMed:11744688). Interacts CC with ADAM15 (PubMed:19718658). Interacts with PRRT2 (By similarity). CC Interacts (via SH3 domain 4) with FCHSD2 (via SH3 domain 2) CC (PubMed:29887380). Interacts (via SH3 domain 1) with DENND2B CC (PubMed:29030480). Interacts (via SH3 domains) with CBL (By CC similarity). Isoform 2: Interacts with CBL and DNM1 (PubMed:21712076). CC Isoform 2: Interacts with LMNA (PubMed:29599122). Isoform 2: Interacts CC with importin subunit KPNA1; this is likely to mediate its import into CC the nucleus (PubMed:29599122). Interacts with DNM2 (PubMed:32315611). CC {ECO:0000250|UniProtKB:Q9WVE9, ECO:0000250|UniProtKB:Q9Z0R4, CC ECO:0000269|PubMed:11584276, ECO:0000269|PubMed:11744688, CC ECO:0000269|PubMed:12006984, ECO:0000269|PubMed:19718658, CC ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:20946875, CC ECO:0000269|PubMed:21712076, ECO:0000269|PubMed:22484487, CC ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:29030480, CC ECO:0000269|PubMed:29599122, ECO:0000269|PubMed:29887380, CC ECO:0000269|PubMed:32315611}. CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein CC A36 (PubMed:27670116). {ECO:0000269|PubMed:27670116}. CC -!- INTERACTION: CC Q15811; P63010: AP2B1; NbExp=2; IntAct=EBI-602041, EBI-432924; CC Q15811; P22681: CBL; NbExp=12; IntAct=EBI-602041, EBI-518228; CC Q15811; P60953-1: CDC42; NbExp=2; IntAct=EBI-602041, EBI-3625591; CC Q15811; Q9NRI5: DISC1; NbExp=4; IntAct=EBI-602041, EBI-529989; CC Q15811; P50570: DNM2; NbExp=2; IntAct=EBI-602041, EBI-346547; CC Q15811; P42566: EPS15; NbExp=3; IntAct=EBI-602041, EBI-396684; CC Q15811; P61968: LMO4; NbExp=3; IntAct=EBI-602041, EBI-2798728; CC Q15811; O43426: SYNJ1; NbExp=2; IntAct=EBI-602041, EBI-2821539; CC Q15811; Q3UQN2: Fcho2; Xeno; NbExp=3; IntAct=EBI-602041, EBI-6094986; CC Q15811-1; P07355: ANXA2; NbExp=2; IntAct=EBI-8052560, EBI-352622; CC Q15811-2; O15357: INPPL1; NbExp=9; IntAct=EBI-8052395, EBI-1384248; CC Q15811-2; Q925Q9: Sh3kbp1; Xeno; NbExp=4; IntAct=EBI-8052395, EBI-8020091; CC -!- SUBCELLULAR LOCATION: Endomembrane system CC {ECO:0000269|PubMed:11744688}. Synapse, synaptosome CC {ECO:0000250|UniProtKB:Q9WVE9}. Cell projection, lamellipodium CC {ECO:0000269|PubMed:11744688}. Cell membrane CC {ECO:0000269|PubMed:11744688, ECO:0000269|PubMed:20946875}. Membrane, CC clathrin-coated pit {ECO:0000269|PubMed:20946875, CC ECO:0000269|PubMed:29887380}. Recycling endosome CC {ECO:0000269|PubMed:29030480}. Endosome {ECO:0000250|UniProtKB:Q9Z0R4}. CC Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q9Z0R4}. Note=Colocalizes CC with SGIP1 at the plasma membrane in structures corresponding most CC probably to clathrin-coated pits (PubMed:20946875). Colocalizes with CC RAB13 on cytoplasmic vesicles that are most likely recycling endosomes CC (PubMed:29030480). {ECO:0000269|PubMed:20946875, CC ECO:0000269|PubMed:29030480}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000269|PubMed:29599122}. Endomembrane system CC {ECO:0000269|PubMed:21712076}. Nucleus envelope CC {ECO:0000269|PubMed:29599122}. Note=Shuttles between the cytoplasm and CC nucleus in an XPO1/CRM1-dependent manner. CC {ECO:0000269|PubMed:29599122}. CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Endomembrane system CC {ECO:0000269|PubMed:21712076}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=13; CC Comment=Additional isoforms seem to exist. Alternative splicing CC affects domains involved in protein recognition and thus may play a CC role in selecting specific interactions. CC {ECO:0000269|PubMed:11690630, ECO:0000269|PubMed:19777371}; CC Name=1; Synonyms=Long, ITSN-l; CC IsoId=Q15811-1; Sequence=Displayed; CC Name=2; Synonyms=Short, ITSN-s {ECO:0000303|PubMed:29599122}; CC IsoId=Q15811-2; Sequence=VSP_004295; CC Name=3; Synonyms=Short 2, SH3P17; CC IsoId=Q15811-3; Sequence=VSP_004293, VSP_004294, VSP_004295; CC Name=4; CC IsoId=Q15811-4; Sequence=VSP_004294; CC Name=5; Synonyms=ITSN1-22a; CC IsoId=Q15811-5; Sequence=VSP_004293, VSP_047460, VSP_047461; CC Name=6; Synonyms=Long form variant 4, Short form variant 11; CC IsoId=Q15811-6; Sequence=VSP_004293, VSP_053320, VSP_053321; CC Name=7; Synonyms=Short form variant 5; CC IsoId=Q15811-7; Sequence=VSP_004293, VSP_004295; CC Name=8; Synonyms=Long form variant 2; CC IsoId=Q15811-8; Sequence=VSP_004293; CC Name=9; Synonyms=Long form variant 3; CC IsoId=Q15811-9; Sequence=VSP_004293, VSP_053322; CC Name=10; Synonyms=Short form variant 2; CC IsoId=Q15811-10; Sequence=VSP_053317, VSP_004293, VSP_004295; CC Name=11; Synonyms=Short form variant 3; CC IsoId=Q15811-11; Sequence=VSP_053317, VSP_004294, VSP_004295; CC Name=12; Synonyms=Short form variant 10; CC IsoId=Q15811-12; Sequence=VSP_053317, VSP_004293, VSP_004294, CC VSP_004295; CC Name=13; Synonyms=Short form variant 14; CC IsoId=Q15811-13; Sequence=VSP_004293, VSP_053318, VSP_053319; CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed almost exclusively in the CC brain. Isoform 2 is detected in brain, spleen, lung, liver, heart, CC skeletal muscle and kidney. Isoform 5 is primarily expressed in brain, CC spleen, lung and kidney (at protein level) (PubMed:21712076). Isoform 1 CC and isoform 2 are detected in brain (PubMed:10482960). Isoform 2 is CC ubiquitous in adult and fetal tissues with high expression in skeletal CC muscle, heart, spleen, ovary, testis and all fetal tissues tested and CC low expression in thymus, blood, lung, liver and pancreas. Isoform 1 is CC expressed almost exclusively in the brain, in all brain regions. Not CC expressed in the spinal cord (PubMed:9799604, PubMed:21712076, CC PubMed:11690630). {ECO:0000269|PubMed:10482960, CC ECO:0000269|PubMed:11690630, ECO:0000269|PubMed:21712076, CC ECO:0000269|PubMed:9799604}. 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:0000250|UniProtKB:Q9Z0R4}. CC -!- MISCELLANEOUS: [Isoform 6]: Contains a premature stop codon, CC potentially subjected to NMD. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 13]: Contains a premature stop codon, CC potentially subjected to NMD. {ECO:0000305}. CC -!- CAUTION: Studies in clathrin-mediated endocytosis of ITGB1 and TFR used CC a siRNA mixture of ISTN1 and ISTN2, and a Dab2 mutant with impaired CC binding to EH domain-containing proteins EPS15 and ITSN1 suggesting a CC partially overlapping role of the EH domain-containing proteins. CC {ECO:0000305|PubMed:22648170}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC50592.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; AF064244; AAC78611.1; -; mRNA. DR EMBL; AF064247; AAC80437.1; -; Genomic_DNA. DR EMBL; AF064245; AAC80437.1; JOINED; Genomic_DNA. DR EMBL; AF064246; AAC80437.1; JOINED; Genomic_DNA. DR EMBL; AF064243; AAC78610.1; -; mRNA. DR EMBL; AF114488; AAD29953.1; -; mRNA. DR EMBL; AF114487; AAD29952.1; -; mRNA. DR EMBL; DQ679754; ABG74695.1; -; mRNA. DR EMBL; DQ679756; ABG74697.1; -; mRNA. DR EMBL; DQ679757; ABG74698.1; -; mRNA. DR EMBL; EU117382; ABV21755.1; -; mRNA. DR EMBL; EU140799; ABV58335.1; -; mRNA. DR EMBL; EU140800; ABV58336.1; -; mRNA. DR EMBL; EU120733; ABV24866.1; -; mRNA. DR EMBL; EU120734; ABV24867.1; -; mRNA. DR EMBL; EU120735; ABV24868.1; -; mRNA. DR EMBL; EU152331; ABV69555.1; -; mRNA. DR EMBL; DQ386455; ABD72328.1; -; mRNA. DR EMBL; AK300274; BAG62034.1; -; mRNA. DR EMBL; AP000308; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000309; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000310; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000311; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000312; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000313; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC117560; AAI17561.1; -; mRNA. DR EMBL; BC116186; AAI16187.1; -; mRNA. DR EMBL; U61166; AAC50592.1; ALT_INIT; mRNA. DR EMBL; AF180522; AAD53183.1; -; mRNA. DR CCDS; CCDS33545.1; -. [Q15811-1] DR CCDS; CCDS33546.1; -. [Q15811-2] DR CCDS; CCDS82663.1; -. [Q15811-7] DR CCDS; CCDS82664.1; -. [Q15811-8] DR CCDS; CCDS82665.1; -. [Q15811-3] DR CCDS; CCDS82666.1; -. [Q15811-10] DR RefSeq; NP_001001132.1; NM_001001132.1. [Q15811-2] DR RefSeq; NP_001317938.1; NM_001331009.1. [Q15811-7] DR RefSeq; NP_001317939.1; NM_001331010.1. [Q15811-8] DR RefSeq; NP_001317940.1; NM_001331011.1. [Q15811-3] DR RefSeq; NP_001317941.1; NM_001331012.1. [Q15811-10] DR RefSeq; NP_003015.2; NM_003024.2. [Q15811-1] DR RefSeq; XP_011527994.1; XM_011529692.1. [Q15811-12] DR RefSeq; XP_011527995.1; XM_011529693.2. [Q15811-5] DR RefSeq; XP_016883917.1; XM_017028428.1. [Q15811-1] DR RefSeq; XP_016883921.1; XM_017028432.1. [Q15811-9] DR RefSeq; XP_016883922.1; XM_017028433.1. [Q15811-4] DR RefSeq; XP_016883929.1; XM_017028440.1. [Q15811-11] DR PDB; 1KI1; X-ray; 2.30 A; B/D=1229-1581. DR PDB; 2KGR; NMR; -; A=210-312. DR PDB; 2KHN; NMR; -; A=1-111. DR PDB; 3FIA; X-ray; 1.45 A; A=1-111. DR PDB; 3QBV; X-ray; 2.65 A; B/D=1229-1579. DR PDB; 4IIM; X-ray; 1.80 A; A/B=916-970. DR PDB; 5HZI; X-ray; 2.60 A; A/B=1230-1580. DR PDB; 5HZJ; X-ray; 2.60 A; A/B=1230-1580. DR PDB; 5HZK; X-ray; 3.30 A; B/D=1230-1580. DR PDB; 6GBU; X-ray; 3.44 A; B/D/F/H=1074-1138. DR PDB; 6H5T; X-ray; 1.69 A; A/B=741-840. DR PDBsum; 1KI1; -. DR PDBsum; 2KGR; -. DR PDBsum; 2KHN; -. DR PDBsum; 3FIA; -. DR PDBsum; 3QBV; -. DR PDBsum; 4IIM; -. DR PDBsum; 5HZI; -. DR PDBsum; 5HZJ; -. DR PDBsum; 5HZK; -. DR PDBsum; 6GBU; -. DR PDBsum; 6H5T; -. DR AlphaFoldDB; Q15811; -. DR SMR; Q15811; -. DR BioGRID; 112351; 216. DR DIP; DIP-33609N; -. DR IntAct; Q15811; 140. DR MINT; Q15811; -. DR STRING; 9606.ENSP00000370719; -. DR ChEMBL; CHEMBL4523302; -. DR iPTMnet; Q15811; -. DR PhosphoSitePlus; Q15811; -. DR BioMuta; ITSN1; -. DR DMDM; 116242596; -. DR EPD; Q15811; -. DR jPOST; Q15811; -. DR MassIVE; Q15811; -. DR MaxQB; Q15811; -. DR PaxDb; 9606-ENSP00000370719; -. DR PeptideAtlas; Q15811; -. DR ProteomicsDB; 17792; -. DR ProteomicsDB; 1818; -. DR ProteomicsDB; 1824; -. DR ProteomicsDB; 1825; -. DR ProteomicsDB; 1827; -. DR ProteomicsDB; 5114; -. DR ProteomicsDB; 60768; -. [Q15811-1] DR ProteomicsDB; 60769; -. [Q15811-2] DR ProteomicsDB; 60770; -. [Q15811-3] DR ProteomicsDB; 60771; -. [Q15811-4] DR Pumba; Q15811; -. DR ABCD; Q15811; 2 sequenced antibodies. DR Antibodypedia; 7532; 106 antibodies from 19 providers. DR DNASU; 6453; -. DR Ensembl; ENST00000381291.8; ENSP00000370691.4; ENSG00000205726.15. [Q15811-2] DR Ensembl; ENST00000381318.8; ENSP00000370719.3; ENSG00000205726.15. [Q15811-1] DR Ensembl; ENST00000399338.8; ENSP00000382275.4; ENSG00000205726.15. [Q15811-5] DR Ensembl; ENST00000399349.5; ENSP00000382286.1; ENSG00000205726.15. [Q15811-3] DR Ensembl; ENST00000399352.5; ENSP00000382289.1; ENSG00000205726.15. [Q15811-7] DR Ensembl; ENST00000399353.5; ENSP00000382290.1; ENSG00000205726.15. [Q15811-10] DR Ensembl; ENST00000399367.7; ENSP00000382301.3; ENSG00000205726.15. [Q15811-8] DR GeneID; 6453; -. DR KEGG; hsa:6453; -. DR MANE-Select; ENST00000381318.8; ENSP00000370719.3; NM_003024.3; NP_003015.2. DR UCSC; uc002ysw.4; human. [Q15811-1] DR AGR; HGNC:6183; -. DR CTD; 6453; -. DR DisGeNET; 6453; -. DR GeneCards; ITSN1; -. DR HGNC; HGNC:6183; ITSN1. DR HPA; ENSG00000205726; Low tissue specificity. DR MalaCards; ITSN1; -. DR MIM; 602442; gene. DR neXtProt; NX_Q15811; -. DR OpenTargets; ENSG00000205726; -. DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability. DR PharmGKB; PA29981; -. DR VEuPathDB; HostDB:ENSG00000205726; -. DR eggNOG; KOG1029; Eukaryota. DR eggNOG; KOG4305; Eukaryota. DR GeneTree; ENSGT00940000157065; -. DR HOGENOM; CLU_002819_0_0_1; -. DR InParanoid; Q15811; -. DR OMA; XCSDLHL; -. DR OrthoDB; 2910300at2759; -. DR PhylomeDB; Q15811; -. DR TreeFam; TF324293; -. DR PathwayCommons; Q15811; -. DR Reactome; R-HSA-193648; NRAGE signals death through JNK. DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling. DR Reactome; R-HSA-416482; G alpha (12/13) signalling events. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-9013148; CDC42 GTPase cycle. DR Reactome; R-HSA-9013406; RHOQ GTPase cycle. DR Reactome; R-HSA-9013408; RHOG GTPase cycle. DR SignaLink; Q15811; -. DR SIGNOR; Q15811; -. DR BioGRID-ORCS; 6453; 10 hits in 1159 CRISPR screens. DR ChiTaRS; ITSN1; human. DR EvolutionaryTrace; Q15811; -. DR GeneWiki; ITSN1; -. DR GenomeRNAi; 6453; -. DR Pharos; Q15811; Tbio. DR PRO; PR:Q15811; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; Q15811; Protein. DR Bgee; ENSG00000205726; Expressed in sural nerve and 210 other cell types or tissues. DR ExpressionAtlas; Q15811; baseline and differential. DR GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0097708; C:intracellular vesicle; IBA:GO_Central. DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell. DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW. DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. 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; NAS:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProtKB. DR GO; GO:0070064; F:proline-rich region binding; IPI:UniProtKB. 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:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0008104; P:protein localization; IMP:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. 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; PR00499; P67PHOX. 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; Q15811; HS. 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; Host-virus interaction; Membrane; KW Metal-binding; Nucleus; Phosphoprotein; Protein transport; KW Reference proteome; Repeat; SH3 domain; Synapse; Synaptosome; Transport. FT CHAIN 1..1721 FT /note="Intersectin-1" FT /id="PRO_0000080957" 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 740..806 FT /note="SH3 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 913..971 FT /note="SH3 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 1002..1060 FT /note="SH3 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 1074..1138 FT /note="SH3 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 1155..1214 FT /note="SH3 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 1237..1423 FT /note="DH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062" FT DOMAIN 1462..1571 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 1579..1695 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 322..348 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 326..702 FT /note="KLERQ" FT REGION 650..701 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 836..868 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1074..1138 FT /note="Required for interaction with FCHSD2" FT /evidence="ECO:0000269|PubMed:29887380" FT COILED 355..659 FT /evidence="ECO:0000255" FT MOTIF 1104..1127 FT /note="Bipartite nuclear localization signal; in isoform 2" FT /evidence="ECO:0000269|PubMed:29599122" FT COMPBIAS 330..348 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 837..868 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 1667 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1670 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1673 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:23186163" FT MOD_RES 318 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z0R4" FT MOD_RES 687 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9WVE9" FT MOD_RES 897 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Z0R4" FT MOD_RES 901 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 902 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 904 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 978 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9WVE9" FT MOD_RES 986 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 995 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1137 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1144 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1645 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z0R4" FT VAR_SEQ 116..152 FT /note="Missing (in isoform 10, isoform 11 and isoform 12)" FT /evidence="ECO:0000303|PubMed:19777371" FT /id="VSP_053317" FT VAR_SEQ 770..774 FT /note="Missing (in isoform 3, isoform 5, isoform 6, isoform FT 7, isoform 8, isoform 9, isoform 10, isoform 12 and isoform FT 13)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:19777371, FT ECO:0000303|PubMed:21712076, ECO:0000303|PubMed:9630982, FT ECO:0000303|Ref.9" FT /id="VSP_004293" FT VAR_SEQ 910..1025 FT /note="GEKVEGLQAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWF FT PKSYVKLISGPIRKSTSMDSGSSESPASLKRVASPAAKPVVSGEEFIAMYTYESSEQGD FT LTFQQ -> PDFLLHPSMRLGHMQPRIVLLFPDPLQCSTSRLLPMLRPRPGVPFLRSPS FT CQSPSHPSRPISDAAPSVKFTLMPPGRIHPCFLFIPAVNSRNSFLVYFILPGGTLGCFY FT LCLPHYL (in isoform 5)" FT /evidence="ECO:0000303|PubMed:21712076" FT /id="VSP_047460" FT VAR_SEQ 910..919 FT /note="GEKVEGLQAQ -> HGFWFFRESC (in isoform 13)" FT /evidence="ECO:0000305" FT /id="VSP_053318" FT VAR_SEQ 920..1721 FT /note="Missing (in isoform 13)" FT /evidence="ECO:0000305" FT /id="VSP_053319" FT VAR_SEQ 1006..1076 FT /note="Missing (in isoform 3, isoform 4, isoform 11 and FT isoform 12)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:19777371, ECO:0000303|PubMed:9630982, FT ECO:0000303|Ref.9" FT /id="VSP_004294" FT VAR_SEQ 1006..1020 FT /note="EFIAMYTYESSEQGD -> GLWNCWENREFRKKT (in isoform 6)" FT /evidence="ECO:0000303|PubMed:19777371" FT /id="VSP_053320" FT VAR_SEQ 1021..1721 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:19777371" FT /id="VSP_053321" FT VAR_SEQ 1026..1721 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:21712076" FT /id="VSP_047461" FT VAR_SEQ 1221..1721 FT /note="Missing (in isoform 2, isoform 3, isoform 7, isoform FT 10, isoform 11 and isoform 12)" FT /evidence="ECO:0000303|PubMed:10482960, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:19777371, ECO:0000303|PubMed:9630982, FT ECO:0000303|PubMed:9799604, ECO:0000303|Ref.9" FT /id="VSP_004295" FT VAR_SEQ 1392..1447 FT /note="Missing (in isoform 9)" FT /evidence="ECO:0000303|PubMed:19777371" FT /id="VSP_053322" FT VARIANT 1137 FT /note="S -> N (in dbSNP:rs187895245)" FT /evidence="ECO:0000269|PubMed:19777371, FT ECO:0000269|PubMed:9799604" FT /id="VAR_070011" FT MUTAGEN 1078 FT /note="I->K,S: Abolishes interaction with FCHSD2." FT /evidence="ECO:0000269|PubMed:29887380" FT MUTAGEN 1119 FT /note="R->A,E: Abolishes interaction with FCHSD2." FT /evidence="ECO:0000269|PubMed:29887380" FT MUTAGEN 1369 FT /note="M->L: Decreases specificity for CDC42; when FT associated with I-1376." FT /evidence="ECO:0000269|PubMed:12006984" FT MUTAGEN 1376 FT /note="L->I: Decreases specificity for CDC42; when FT associated with L-1369." FT /evidence="ECO:0000269|PubMed:12006984" FT CONFLICT 114 FT /note="A -> P (in Ref. 1; AAC78610/AAC78611 and 3; FT ABG74695/ABG74697/ABG74698)" FT /evidence="ECO:0000305" FT CONFLICT 863 FT /note="E -> G (in Ref. 4; ABD72328)" FT /evidence="ECO:0000305" FT CONFLICT 1088 FT /note="T -> A (in Ref. 9; AAD53183)" FT /evidence="ECO:0000305" FT CONFLICT 1109 FT /note="G -> R (in Ref. 9; AAD53183)" FT /evidence="ECO:0000305" FT CONFLICT 1361 FT /note="A -> E (in Ref. 1; AAC78611 and 8; AAC50592)" FT /evidence="ECO:0000305" FT CONFLICT 1367 FT /note="K -> R (in Ref. 7; AAI16187)" FT /evidence="ECO:0000305" FT CONFLICT 1474 FT /note="S -> N (in Ref. 1; AAC78611 and 8; AAC50592)" FT /evidence="ECO:0000305" FT TURN 12..14 FT /evidence="ECO:0007829|PDB:3FIA" FT HELIX 19..31 FT /evidence="ECO:0007829|PDB:3FIA" FT STRAND 35..37 FT /evidence="ECO:0007829|PDB:2KHN" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:3FIA" FT HELIX 41..48 FT /evidence="ECO:0007829|PDB:3FIA" FT HELIX 49..51 FT /evidence="ECO:0007829|PDB:3FIA" FT HELIX 55..65 FT /evidence="ECO:0007829|PDB:3FIA" FT STRAND 70..73 FT /evidence="ECO:0007829|PDB:3FIA" FT HELIX 75..89 FT /evidence="ECO:0007829|PDB:3FIA" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:3FIA" FT STRAND 215..217 FT /evidence="ECO:0007829|PDB:2KGR" FT HELIX 219..230 FT /evidence="ECO:0007829|PDB:2KGR" FT STRAND 239..241 FT /evidence="ECO:0007829|PDB:2KGR" FT HELIX 242..250 FT /evidence="ECO:0007829|PDB:2KGR" FT HELIX 256..266 FT /evidence="ECO:0007829|PDB:2KGR" FT STRAND 272..275 FT /evidence="ECO:0007829|PDB:2KGR" FT HELIX 276..290 FT /evidence="ECO:0007829|PDB:2KGR" FT HELIX 301..303 FT /evidence="ECO:0007829|PDB:2KGR" FT TURN 306..309 FT /evidence="ECO:0007829|PDB:2KGR" FT STRAND 741..747 FT /evidence="ECO:0007829|PDB:6H5T" FT STRAND 766..769 FT /evidence="ECO:0007829|PDB:6H5T" FT STRAND 775..778 FT /evidence="ECO:0007829|PDB:6H5T" FT STRAND 780..782 FT /evidence="ECO:0007829|PDB:6H5T" FT STRAND 784..789 FT /evidence="ECO:0007829|PDB:6H5T" FT STRAND 792..797 FT /evidence="ECO:0007829|PDB:6H5T" FT HELIX 798..800 FT /evidence="ECO:0007829|PDB:6H5T" FT STRAND 801..803 FT /evidence="ECO:0007829|PDB:6H5T" FT STRAND 916..922 FT /evidence="ECO:0007829|PDB:4IIM" FT STRAND 939..945 FT /evidence="ECO:0007829|PDB:4IIM" FT STRAND 947..954 FT /evidence="ECO:0007829|PDB:4IIM" FT STRAND 957..962 FT /evidence="ECO:0007829|PDB:4IIM" FT HELIX 963..965 FT /evidence="ECO:0007829|PDB:4IIM" FT STRAND 966..969 FT /evidence="ECO:0007829|PDB:4IIM" FT STRAND 1078..1081 FT /evidence="ECO:0007829|PDB:6GBU" FT STRAND 1100..1106 FT /evidence="ECO:0007829|PDB:6GBU" FT STRAND 1110..1117 FT /evidence="ECO:0007829|PDB:6GBU" FT STRAND 1119..1121 FT /evidence="ECO:0007829|PDB:6GBU" FT STRAND 1125..1129 FT /evidence="ECO:0007829|PDB:6GBU" FT HELIX 1130..1132 FT /evidence="ECO:0007829|PDB:6GBU" FT STRAND 1133..1136 FT /evidence="ECO:0007829|PDB:6GBU" FT HELIX 1233..1262 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1264..1269 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1271..1273 FT /evidence="ECO:0007829|PDB:3QBV" FT HELIX 1275..1282 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1285..1306 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1308..1310 FT /evidence="ECO:0007829|PDB:3QBV" FT HELIX 1316..1322 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1323..1327 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1328..1349 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1351..1361 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1364..1366 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1371..1374 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1377..1393 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1403..1437 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1444..1447 FT /evidence="ECO:0007829|PDB:5HZJ" FT STRAND 1451..1454 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1456..1460 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1463..1466 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1472..1474 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1479..1493 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1511..1513 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1522..1524 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1525..1528 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1531..1533 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1541..1544 FT /evidence="ECO:0007829|PDB:1KI1" FT STRAND 1547..1550 FT /evidence="ECO:0007829|PDB:1KI1" FT HELIX 1556..1577 FT /evidence="ECO:0007829|PDB:1KI1" SQ SEQUENCE 1721 AA; 195422 MW; FC4DE644D8BEA2BE CRC64; MAQFPTPFGG SLDIWAITVE ERAKHDQQFH SLKPISGFIT GDQARNFFFQ SGLPQPVLAQ IWALADMNND GRMDQVEFSI AMKLIKLKLQ GYQLPSALPP VMKQQPVAIS SAPAFGMGGI ASMPPLTAVA PVPMGSIPVV GMSPTLVSSV PTAAVPPLAN GAPPVIQPLP AFAHPAATLP KSSSFSRSGP GSQLNTKLQK AQSFDVASVP PVAEWAVPQS SRLKYRQLFN SHDKTMSGHL TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP PEYIPPSFRR VRSGSGISVI SSTSVDQRLP EEPVLEDEQQ QLEKKLPVTF EDKKRENFER GNLELEKRRQ ALLEQQRKEQ ERLAQLERAE QERKERERQE QERKRQLELE KQLEKQRELE RQREEERRKE IERREAAKRE LERQRQLEWE RNRRQELLNQ RNKEQEDIVV LKAKKKTLEF ELEALNDKKH QLEGKLQDIR CRLTTQRQEI ESTNKSRELR IAEITHLQQQ LQESQQMLGR LIPEKQILND QLKQVQQNSL HRDSLVTLKR ALEAKELARQ HLRDQLDEVE KETRSKLQEI DIFNNQLKEL REIHNKQQLQ KQKSMEAERL KQKEQERKII ELEKQKEEAQ RRAQERDKQW LEHVQQEDEH QRPRKLHEEE KLKREESVKK KDGEEKGKQE AQDKLGRLFH QHQEPAKPAV QAPWSTAEKG PLTISAQENV KVVYYRALYP FESRSHDEIT IQPGDIVMVK GEWVDESQTG EPGWLGGELK GKTGWFPANY AEKIPENEVP APVKPVTDST SAPAPKLALR ETPAPLAVTS SEPSTTPNNW ADFSSTWPTS TNEKPETDNW DAWAAQPSLT VPSAGQLRQR SAFTPATATG SSPSPVLGQG EKVEGLQAQA LYPWRAKKDN HLNFNKNDVI TVLEQQDMWW FGEVQGQKGW FPKSYVKLIS GPIRKSTSMD SGSSESPASL KRVASPAAKP VVSGEEFIAM YTYESSEQGD LTFQQGDVIL VTKKDGDWWT GTVGDKAGVF PSNYVRLKDS EGSGTAGKTG SLGKKPEIAQ VIASYTATGP EQLTLAPGQL ILIRKKNPGG WWEGELQARG KKRQIGWFPA NYVKLLSPGT SKITPTEPPK STALAAVCQV IGMYDYTAQN DDELAFNKGQ IINVLNKEDP DWWKGEVNGQ VGLFPSNYVK LTTDMDPSQQ WCSDLHLLDM LTPTERKRQG YIHELIVTEE NYVNDLQLVT EIFQKPLMES ELLTEKEVAM IFVNWKELIM CNIKLLKALR VRKKMSGEKM PVKMIGDILS AQLPHMQPYI RFCSRQLNGA ALIQQKTDEA PDFKEFVKRL AMDPRCKGMP LSSFILKPMQ RVTRYPLIIK NILENTPENH PDHSHLKHAL EKAEELCSQV NEGVREKENS DRLEWIQAHV QCEGLSEQLV FNSVTNCLGP RKFLHSGKLY KAKSNKELYG FLFNDFLLLT QITKPLGSSG TDKVFSPKSN LQYKMYKTPI FLNEVLVKLP TDPSGDEPIF HISHIDRVYT LRAESINERT AWVQKIKAAS ELYIETEKKK REKAYLVRSQ RATGIGRLMV NVVEGIELKP CRSHGKSNPY CEVTMGSQCH ITKTIQDTLN PKWNSNCQFF IRDLEQEVLC ITVFERDQFS PDDFLGRTEI RVADIKKDQG SKGPVTKCLL LHEVPTGEIV VRLDLQLFDE P //