ITSN1_HUMAN
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 03-AUG-2022, entry version 223.
DE RecName: Full=Intersectin-1;
DE AltName: Full=SH3 domain-containing protein 1A {ECO:0000303|PubMed:9465890};
DE AltName: Full=SH3P17;
GN Name=ITSN1;
GN Synonyms=ITSN {ECO:0000303|PubMed:10482960, ECO:0000303|PubMed:9799604},
GN 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 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 [30] {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 guanine nucleotide exchange factor (GEF) for
CC CDC42, and thereby stimulates actin nucleation mediated by WASL and the
CC 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;
CC Evidence={ECO:0000255|PROSITE-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). {ECO:0000250|UniProtKB:Q9WVE9,
CC ECO:0000250|UniProtKB:Q9Z0R4, ECO:0000269|PubMed:11584276,
CC ECO:0000269|PubMed:11744688, ECO:0000269|PubMed:12006984,
CC ECO:0000269|PubMed:19718658, ECO:0000269|PubMed:20448150,
CC ECO:0000269|PubMed:20946875, ECO:0000269|PubMed:21712076,
CC ECO:0000269|PubMed:22484487, ECO:0000269|PubMed:22648170,
CC ECO:0000269|PubMed:29030480, ECO:0000269|PubMed:29599122,
CC ECO:0000269|PubMed:29887380}.
CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein
CC A36 (PubMed:27670116). {ECO:0000269|PubMed:27670116}.
CC -!- INTERACTION:
CC Q15811; P63010: AP2B1; NbExp=3; 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; 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 ---------------------------------------------------------------------------
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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; 203.
DR DIP; DIP-33609N; -.
DR IntAct; Q15811; 77.
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; Q15811; -.
DR PeptideAtlas; Q15811; -.
DR PRIDE; 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 ABCD; Q15811; 2 sequenced antibodies.
DR Antibodypedia; 7532; 89 antibodies from 18 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 CTD; 6453; -.
DR DisGeNET; 6453; -.
DR GeneCards; ITSN1; -.
DR HGNC; HGNC:6183; ITSN1.
DR HPA; ENSG00000205726; Low tissue specificity.
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; WEGELQX; -.
DR OrthoDB; 807060at2759; -.
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 1079 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 208 other tissues.
DR ExpressionAtlas; Q15811; baseline and differential.
DR Genevisible; Q15811; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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: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:UniProtKB.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
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: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: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; 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; 2.
DR Pfam; PF07653; SH3_2; 2.
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; 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
