ECT2_HUMAN
ID ECT2_HUMAN Reviewed; 914 AA.
AC Q9H8V3; Q0MT80; Q2M269; Q6U836; Q9NSV8; Q9NVW9;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 4.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Protein ECT2;
DE AltName: Full=Epithelial cell-transforming sequence 2 oncogene;
GN Name=ECT2;
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 [MRNA] (ISOFORM 2), FUNCTION, PHOSPHORYLATION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=10579713; DOI=10.1083/jcb.147.5.921;
RA Tatsumoto T., Xie X., Blumenthal R., Okamoto I., Miki T.;
RT "Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M
RT phases, and involved in cytokinesis.";
RL J. Cell Biol. 147:921-928(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=14587037; DOI=10.1002/jcb.10688;
RA Saito S., Tatsumoto T., Lorenzi M.V., Chedid M., Kapoor V., Sakata H.,
RA Rubin J.S., Miki T.;
RT "Rho exchange factor ECT2 is induced by growth factors and regulates
RT cytokinesis through the N-terminal cell cycle regulator-related domains.";
RL J. Cell. Biochem. 90:819-836(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH PKP4, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17115030; DOI=10.1038/ncb1504;
RA Wolf A., Keil R., Gotzl O., Mun A., Schwarze K., Lederer M.,
RA Huttelmaier S., Hatzfeld M.;
RT "The armadillo protein p0071 regulates Rho signalling during cytokinesis.";
RL Nat. Cell Biol. 8:1432-1440(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Teratocarcinoma, and Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 662-914 (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP FUNCTION, HOMODIMERIZATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 379-ARG--ARG-381; 402-ARG--ARG-404 AND 596-PRO--ARG-599.
RX PubMed=14645260; DOI=10.1074/jbc.m306725200;
RA Saito S., Liu X.F., Kamijo K., Raziuddin R., Tatsumoto T., Okamoto I.,
RA Chen X., Lee C.C., Lorenzi M.V., Ohara N., Miki T.;
RT "Deregulation and mislocalization of the cytokinesis regulator ECT2
RT activate the Rho signaling pathways leading to malignant transformation.";
RL J. Biol. Chem. 279:7169-7179(2004).
RN [9]
RP FUNCTION, INTERACTION WITH PARD3; PARD6A; PARD6B AND PRKCQ, INDUCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15254234; DOI=10.1128/mcb.24.15.6665-6675.2004;
RA Liu X.F., Ishida H., Raziuddin R., Miki T.;
RT "Nucleotide exchange factor ECT2 interacts with the polarity protein
RT complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta
RT activity.";
RL Mol. Cell. Biol. 24:6665-6675(2004).
RN [10]
RP FUNCTION, HOMODIMERIZATION, HOMOOLIGOMERIZATION, AND MUTAGENESIS OF
RP TRP-336.
RX PubMed=15545273; DOI=10.1074/jbc.m409298200;
RA Kim J.E., Billadeau D.D., Chen J.;
RT "The tandem BRCT domains of Ect2 are required for both negative and
RT positive regulation of Ect2 in cytokinesis.";
RL J. Biol. Chem. 280:5733-5739(2005).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15642749; DOI=10.1083/jcb.200408085;
RA Oceguera-Yanez F., Kimura K., Yasuda S., Higashida C., Kitamura T.,
RA Hiraoka Y., Haraguchi T., Narumiya S.;
RT "Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in
RT mitosis.";
RL J. Cell Biol. 168:221-232(2005).
RN [12]
RP FUNCTION, INTERACTION WITH RACGAP1, MUTAGENESIS OF THR-373, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16103226; DOI=10.1083/jcb.200501097;
RA Yuce O., Piekny A., Glotzer M.;
RT "An ECT2-centralspindlin complex regulates the localization and function of
RT RhoA.";
RL J. Cell Biol. 170:571-582(2005).
RN [13]
RP INTERACTION WITH RACGAP1.
RX PubMed=16129829; DOI=10.1073/pnas.0504145102;
RA Zhao W.-M., Fang G.;
RT "MgcRacGAP controls the assembly of the contractile ring and the initiation
RT of cytokinesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13158-13163(2005).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16495035; DOI=10.1016/j.cellsig.2006.01.007;
RA Liu X.F., Ohno S., Miki T.;
RT "Nucleotide exchange factor ECT2 regulates epithelial cell polarity.";
RL Cell. Signal. 18:1604-1615(2006).
RN [15]
RP FUNCTION, IDENTIFICATION IN THE CENTRALSPINDLIN COMPLEX, INTERACTION WITH
RP KIF23 AND RACGAP1, AND SUBCELLULAR LOCATION.
RX PubMed=16236794; DOI=10.1091/mbc.e05-06-0569;
RA Kamijo K., Ohara N., Abe M., Uchimura T., Hosoya H., Lee J.S., Miki T.;
RT "Dissecting the role of Rho-mediated signaling in contractile ring
RT formation.";
RL Mol. Biol. Cell 17:43-55(2006).
RN [16]
RP FUNCTION, HOMODIMERIZATION, PHOSPHORYLATION AT THR-373, AND MUTAGENESIS OF
RP THR-373.
RX PubMed=16170345; DOI=10.1038/sj.onc.1209078;
RA Hara T., Abe M., Inoue H., Yu L.R., Veenstra T.D., Kang Y.H., Lee K.S.,
RA Miki T.;
RT "Cytokinesis regulator ECT2 changes its conformation through
RT phosphorylation at Thr-341 in G2/M phase.";
RL Oncogene 25:566-578(2006).
RN [17]
RP PHOSPHORYLATION AT THR-444, INTERACTION WITH PLK1, AND MUTAGENESIS OF
RP THR-444 AND THR-846.
RX PubMed=16247472; DOI=10.1038/sj.onc.1209124;
RA Niiya F., Tatsumoto T., Lee K.S., Miki T.;
RT "Phosphorylation of the cytokinesis regulator ECT2 at G2/M phase stimulates
RT association of the mitotic kinase Plk1 and accumulation of GTP-bound
RT RhoA.";
RL Oncogene 25:827-837(2006).
RN [18]
RP INTERACTION WITH RAB11FIP3.
RX PubMed=18511905; DOI=10.1038/emboj.2008.112;
RA Simon G.C., Schonteich E., Wu C.C., Piekny A., Ekiert D., Yu X.,
RA Gould G.W., Glotzer M., Prekeris R.;
RT "Sequential Cyk-4 binding to ECT2 and FIP3 regulates cleavage furrow
RT ingression and abscission during cytokinesis.";
RL EMBO J. 27:1791-1803(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-370; THR-373;
RP SER-376; SER-842 AND THR-846, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [21]
RP FUNCTION.
RX PubMed=19129481; DOI=10.1091/mbc.e08-01-0001;
RA Asiedu M., Wu D., Matsumura F., Wei Q.;
RT "Centrosome/spindle pole-associated protein regulates cytokinesis via
RT promoting the recruitment of MyoGEF to the central spindle.";
RL Mol. Biol. Cell 20:1428-1440(2009).
RN [22]
RP FUNCTION, INTERACTION WITH PARD6A AND PRKCI, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=19617897; DOI=10.1038/onc.2009.217;
RA Justilien V., Fields A.P.;
RT "Ect2 links the PKCiota-Par6alpha complex to Rac1 activation and cellular
RT transformation.";
RL Oncogene 28:3597-3607(2009).
RN [23]
RP FUNCTION, INTERACTION WITH KIF23 AND RACGAP1, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF THR-184 AND LYS-226.
RX PubMed=19468300; DOI=10.1371/journal.pbio.1000110;
RA Wolfe B.A., Takaki T., Petronczki M., Glotzer M.;
RT "Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF
RT complex to initiate cleavage furrow formation.";
RL PLoS Biol. 7:E1000110-E1000110(2009).
RN [24]
RP INTERACTION WITH RACGAP1.
RX PubMed=19468302; DOI=10.1371/journal.pbio.1000111;
RA Burkard M.E., Maciejowski J., Rodriguez-Bravo V., Repka M., Lowery D.M.,
RA Clauser K.R., Zhang C., Shokat K.M., Carr S.A., Yaffe M.B.,
RA Jallepalli P.V.;
RT "Plk1 self-organization and priming phosphorylation of HsCYK-4 at the
RT spindle midzone regulate the onset of division in human cells.";
RL PLoS Biol. 7:E1000111-E1000111(2009).
RN [25]
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359, AND IDENTIFICATION BY
RP 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 [27]
RP FUNCTION, PHOSPHORYLATION AT THR-359, MUTAGENESIS OF THR-359, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=21189248; DOI=10.1074/jbc.m110.196113;
RA Justilien V., Jameison L., Der C.J., Rossman K.L., Fields A.P.;
RT "Oncogenic activity of Ect2 is regulated through protein kinase C iota-
RT mediated phosphorylation.";
RL J. Biol. Chem. 286:8149-8157(2011).
RN [28]
RP FUNCTION, AND INDUCTION.
RX PubMed=21373644; DOI=10.1371/journal.pone.0017108;
RA Srougi M.C., Burridge K.;
RT "The nuclear guanine nucleotide exchange factors Ect2 and Net1 regulate
RT RhoB-mediated cell death after DNA damage.";
RL PLoS ONE 6:E17108-E17108(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-367; SER-716;
RP SER-861 AND SER-866, 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 [32]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-611, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 268-361.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the second BRCT domain of epithelial cell
RT transforming 2 (ECT2).";
RL Submitted (JAN-2010) to the PDB data bank.
RN [34] {ECO:0007744|PDB:4N40}
RP X-RAY CRYSTALLOGRAPHY (3.11 ANGSTROMS) OF 45-356, FUNCTION, ACTIVITY
RP REGULATION, INTERACTION WITH RACGAP1, AND MUTAGENESIS OF THR-184 AND
RP LYS-226.
RX PubMed=25068414; DOI=10.1016/j.febslet.2014.07.019;
RA Zou Y., Shao Z., Peng J., Li F., Gong D., Wang C., Zuo X., Zhang Z., Wu J.,
RA Shi Y., Gong Q.;
RT "Crystal structure of triple-BRCT-domain of ECT2 and insights into the
RT binding characteristics to CYK-4.";
RL FEBS Lett. 588:2911-2920(2014).
RN [35] {ECO:0007744|PDB:6L30}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 173-865, FUNCTION, ACTIVITY
RP REGULATION, INTERACTION WITH RHOA, DOMAIN, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND MUTAGENESIS OF TRP-338; ARG-488; ARG-570; ALA-573;
RP ARG-586; PRO-601; PHE-652; TYR-656; ARG-670; PRO-734 AND CYS-796.
RX PubMed=31888991; DOI=10.1073/pnas.1913054117;
RA Chen M., Pan H., Sun L., Shi P., Zhang Y., Li L., Huang Y., Chen J.,
RA Jiang P., Fang X., Wu C., Chen Z.;
RT "Structure and regulation of human epithelial cell transforming 2
RT protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:1027-1035(2020).
RN [36]
RP VARIANT [LARGE SCALE ANALYSIS] PRO-833.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) that catalyzes the
CC exchange of GDP for GTP. Promotes guanine nucleotide exchange on the
CC Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42.
CC Required for signal transduction pathways involved in the regulation of
CC cytokinesis. Component of the centralspindlin complex that serves as a
CC microtubule-dependent and Rho-mediated signaling required for the
CC myosin contractile ring formation during the cell cycle cytokinesis.
CC Regulates the translocation of RHOA from the central spindle to the
CC equatorial region. Plays a role in the control of mitotic spindle
CC assembly; regulates the activation of CDC42 in metaphase for the
CC process of spindle fibers attachment to kinetochores before chromosome
CC congression. Involved in the regulation of epithelial cell polarity;
CC participates in the formation of epithelial tight junctions in a
CC polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner.
CC Plays a role in the regulation of neurite outgrowth. Inhibits
CC phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the
CC activity of RAC1 through its association with the oncogenic PARD6A-
CC PRKCI complex in cancer cells, thereby acting to coordinately drive
CC tumor cell proliferation and invasion. Also stimulates genotoxic
CC stress-induced RHOB activity in breast cancer cells leading to their
CC cell death. {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:14645260,
CC ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:15545273,
CC ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226,
CC ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16236794,
CC ECO:0000269|PubMed:16495035, ECO:0000269|PubMed:19129481,
CC ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19617897,
CC ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21373644,
CC ECO:0000269|PubMed:25068414, ECO:0000269|PubMed:31888991}.
CC -!- ACTIVITY REGULATION: Autoinhibited by the C-terminal PH domain which
CC folds back and binds to the surface of the DH domain, blocking binding
CC of RHOA to the catalytic center of the DH domain (PubMed:31888991). The
CC 2nd BRCT domain is also involved in inhibition, probably by helping to
CC impede RHOA binding (PubMed:31888991). Allosterically activated by
CC binding of activated GTP-bound RHOA to the PH domain which stimulates
CC the release of PH inhibition and promotes the binding of substrate RHOA
CC to the catalytic center (PubMed:31888991). Binding of phosphorylated
CC RACGAP1 to the N-terminal BRCT domain-containing region also releases
CC autoinhibition (PubMed:25068414). {ECO:0000269|PubMed:25068414,
CC ECO:0000269|PubMed:31888991}.
CC -!- SUBUNIT: Homodimer (PubMed:15545273, PubMed:14645260, PubMed:16170345).
CC Homooligomer (PubMed:15545273). Found in the centralspindlin complex
CC (PubMed:16236794). Interacts with NR1I3 (By similarity). Interacts
CC (Thr-359 phosphorylated form) with PARD6A; the interaction is observed
CC in cancer cells (PubMed:15254234, PubMed:19617897). Interacts (Thr-359
CC phosphorylated form) with PRKCI; the interaction is observed in cancer
CC cells (PubMed:19617897). Interacts with PKP4; the interaction is
CC observed at the midbody (PubMed:22814378). Interacts with RACGAP1/CYK4;
CC the interaction is direct, occurs in a microtubule-dependent manner,
CC occurs at anaphase and during cytokinesis, is inhibited in metaphase by
CC phosphorylation of ECT2 on Thr-373 and is stimulated in early anaphase
CC by dephosphorylation of ECT2 probably on Thr-373 through CDK1 activity
CC (PubMed:16103226, PubMed:16129829, PubMed:16236794, PubMed:19468300,
CC PubMed:19468302, PubMed:25068414). Interacts with PLK1; the interaction
CC is stimulated upon its phosphorylation on Thr-444 (PubMed:16247472).
CC Interacts with RHOA; the interaction results in allosteric activation
CC of ECT2 (PubMed:31888991). Interacts with KIF23, PARD3, PARD6B and
CC PRKCQ (PubMed:15254234, PubMed:16236794).
CC {ECO:0000250|UniProtKB:Q07139, ECO:0000269|PubMed:14645260,
CC ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:15545273,
CC ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829,
CC ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16236794,
CC ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:19468300,
CC ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19617897,
CC ECO:0000269|PubMed:22814378, ECO:0000269|PubMed:25068414,
CC ECO:0000269|PubMed:31888991}.
CC -!- INTERACTION:
CC Q9H8V3; P12830: CDH1; NbExp=3; IntAct=EBI-1054039, EBI-727477;
CC Q9H8V3; P35221: CTNNA1; NbExp=3; IntAct=EBI-1054039, EBI-701918;
CC Q9H8V3; Q02241: KIF23; NbExp=2; IntAct=EBI-1054039, EBI-306852;
CC Q9H8V3; P16333: NCK1; NbExp=3; IntAct=EBI-1054039, EBI-389883;
CC Q9H8V3; O00444: PLK4; NbExp=3; IntAct=EBI-1054039, EBI-746202;
CC Q9H8V3; Q9H0H5: RACGAP1; NbExp=15; IntAct=EBI-1054039, EBI-717233;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton,
CC spindle. Cleavage furrow. Midbody. Cell junction. Cell junction, tight
CC junction. Note=Sequestered within the nucleus during interphase.
CC Dispersed throughout the cytoplasm upon breakdown of the nuclear
CC envelope during mitosis. Colocalizes with the centralspindlin complex
CC to the mitotic spindles during anaphase/metaphase, the cleavage furrow
CC during telophase and at the midbody at the end of cytokinesis.
CC Colocalized with RhoA at the midbody. Its subcellular localization to
CC tight junction is increased by calcium. Localized predominantly in the
CC cytoplasm of numerous carcinoma cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9H8V3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H8V3-2; Sequence=VSP_041976, VSP_041977;
CC Name=3;
CC IsoId=Q9H8V3-3; Sequence=VSP_041978;
CC Name=4;
CC IsoId=Q9H8V3-4; Sequence=VSP_041977;
CC -!- TISSUE SPECIFICITY: Expressed in lung epithelial cells (at protein
CC level). Expressed in squamous cell carcinoma, primary non-small cell
CC lung cancer tumors and lung adenocarcinoma.
CC {ECO:0000269|PubMed:19617897}.
CC -!- INDUCTION: Up-regulated by calcium in cells forming cell-cell contact
CC sites. Up-regulated by DNA damaging agents like H(2)O(2) or ionizing
CC radiation (IR). {ECO:0000269|PubMed:15254234,
CC ECO:0000269|PubMed:21373644}.
CC -!- DOMAIN: The BRCT domains 1 and 2 are required for intramolecular
CC interaction, but not for intermolecular oligomerization
CC (PubMed:15545273). The BRCT domains negatively inhibit its GEF activity
CC in interphase cells (PubMed:15545273, PubMed:31888991). The same BRCT
CC domains may act as a positive regulatory motif for the completion of
CC cytokinesis after the breakdown of nuclear membrane during mitosis
CC (PubMed:15545273). {ECO:0000269|PubMed:15545273,
CC ECO:0000269|PubMed:31888991}.
CC -!- PTM: Phosphorylated by PLK1 in vitro. Hyperphosphorylated during the G2
CC phase of the cell cycle. Phosphorylation at Thr-373 occurs during the
CC G2/M phase, relieves its auto-inhibition status and stimulates its GEF
CC activity. Phosphorylation at Thr-444 in G2/M phase is required for
CC subsequent binding with PLK1 and Rho exchange activation.
CC Dephosphorylated at the time of cytokinesis. Phosphorylation at Thr-359
CC is required for its transformation activity in cancer cells.
CC {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:16170345,
CC ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:21189248}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91624.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ECT2ID40400ch3q26.html";
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DR EMBL; AY376439; AAQ83675.1; -; mRNA.
DR EMBL; DQ847274; ABH10140.1; -; mRNA.
DR EMBL; AK001323; BAA91624.1; ALT_INIT; mRNA.
DR EMBL; AK023267; BAB14498.1; -; mRNA.
DR EMBL; AK314581; BAG37157.1; -; mRNA.
DR EMBL; AC108667; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC112086; AAI12087.1; -; mRNA.
DR EMBL; AL137710; CAB70886.1; -; mRNA.
DR CCDS; CCDS3220.1; -. [Q9H8V3-4]
DR CCDS; CCDS58860.1; -. [Q9H8V3-1]
DR CCDS; CCDS87168.1; -. [Q9H8V3-2]
DR RefSeq; NP_001245244.1; NM_001258315.1. [Q9H8V3-1]
DR RefSeq; NP_001245245.1; NM_001258316.1. [Q9H8V3-4]
DR RefSeq; NP_060568.3; NM_018098.5. [Q9H8V3-4]
DR RefSeq; XP_011510816.1; XM_011512514.2. [Q9H8V3-3]
DR PDB; 3L46; X-ray; 1.48 A; A/B=268-361.
DR PDB; 4N40; X-ray; 3.11 A; A=45-356.
DR PDB; 6L30; X-ray; 2.80 A; A=173-865.
DR PDBsum; 3L46; -.
DR PDBsum; 4N40; -.
DR PDBsum; 6L30; -.
DR AlphaFoldDB; Q9H8V3; -.
DR SMR; Q9H8V3; -.
DR BioGRID; 108223; 872.
DR CORUM; Q9H8V3; -.
DR DIP; DIP-47496N; -.
DR IntAct; Q9H8V3; 23.
DR MINT; Q9H8V3; -.
DR STRING; 9606.ENSP00000376457; -.
DR iPTMnet; Q9H8V3; -.
DR MetOSite; Q9H8V3; -.
DR PhosphoSitePlus; Q9H8V3; -.
DR BioMuta; ECT2; -.
DR DMDM; 357529579; -.
DR EPD; Q9H8V3; -.
DR jPOST; Q9H8V3; -.
DR MassIVE; Q9H8V3; -.
DR MaxQB; Q9H8V3; -.
DR PaxDb; Q9H8V3; -.
DR PeptideAtlas; Q9H8V3; -.
DR PRIDE; Q9H8V3; -.
DR ProteomicsDB; 81243; -. [Q9H8V3-1]
DR ProteomicsDB; 81244; -. [Q9H8V3-2]
DR ProteomicsDB; 81245; -. [Q9H8V3-3]
DR Antibodypedia; 33733; 387 antibodies from 32 providers.
DR DNASU; 1894; -.
DR Ensembl; ENST00000232458.9; ENSP00000232458.5; ENSG00000114346.14. [Q9H8V3-4]
DR Ensembl; ENST00000392692.8; ENSP00000376457.3; ENSG00000114346.14. [Q9H8V3-1]
DR Ensembl; ENST00000417960.5; ENSP00000415876.1; ENSG00000114346.14. [Q9H8V3-2]
DR Ensembl; ENST00000441497.6; ENSP00000412259.2; ENSG00000114346.14. [Q9H8V3-4]
DR Ensembl; ENST00000540509.5; ENSP00000443160.2; ENSG00000114346.14. [Q9H8V3-4]
DR GeneID; 1894; -.
DR KEGG; hsa:1894; -.
DR MANE-Select; ENST00000392692.8; ENSP00000376457.3; NM_001258315.2; NP_001245244.1.
DR UCSC; uc003fih.4; human. [Q9H8V3-1]
DR CTD; 1894; -.
DR DisGeNET; 1894; -.
DR GeneCards; ECT2; -.
DR HGNC; HGNC:3155; ECT2.
DR HPA; ENSG00000114346; Low tissue specificity.
DR MIM; 600586; gene.
DR neXtProt; NX_Q9H8V3; -.
DR OpenTargets; ENSG00000114346; -.
DR PharmGKB; PA27600; -.
DR VEuPathDB; HostDB:ENSG00000114346; -.
DR eggNOG; KOG3524; Eukaryota.
DR GeneTree; ENSGT00940000156299; -.
DR HOGENOM; CLU_008187_0_0_1; -.
DR InParanoid; Q9H8V3; -.
DR OMA; WFWISVQ; -.
DR OrthoDB; 557169at2759; -.
DR TreeFam; TF101161; -.
DR PathwayCommons; Q9H8V3; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR SignaLink; Q9H8V3; -.
DR SIGNOR; Q9H8V3; -.
DR BioGRID-ORCS; 1894; 633 hits in 1089 CRISPR screens.
DR ChiTaRS; ECT2; human.
DR EvolutionaryTrace; Q9H8V3; -.
DR GeneWiki; ECT2; -.
DR GenomeRNAi; 1894; -.
DR Pharos; Q9H8V3; Tbio.
DR PRO; PR:Q9H8V3; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9H8V3; protein.
DR Bgee; ENSG00000114346; Expressed in secondary oocyte and 165 other tissues.
DR ExpressionAtlas; Q9H8V3; baseline and differential.
DR Genevisible; Q9H8V3; HS.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0005938; C:cell cortex; IBA:GO_Central.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0097149; C:centralspindlin complex; IDA:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IMP:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0090630; P:activation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0032147; P:activation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0070830; P:bicellular tight junction assembly; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:UniProtKB.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0051988; P:regulation of attachment of spindle microtubules to kinetochore; IMP:UniProtKB.
DR GO; GO:2000431; P:regulation of cytokinesis, actomyosin contractile ring assembly; IEA:InterPro.
DR GO; GO:0045859; P:regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.40.50.10190; -; 3.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR026817; Ect2.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR011993; PH-like_dom_sf.
DR PANTHER; PTHR16777; PTHR16777; 1.
DR Pfam; PF00533; BRCT; 1.
DR Pfam; PF12738; PTCB-BRCT; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00292; BRCT; 2.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF52113; SSF52113; 2.
DR PROSITE; PS50172; BRCT; 2.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Cell junction; Cytoplasm; Cytoskeleton; Differentiation;
KW Guanine-nucleotide releasing factor; Isopeptide bond; Neurogenesis;
KW Nucleus; Oncogene; Phosphoprotein; Protein transport; Reference proteome;
KW Repeat; Tight junction; Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..914
FT /note="Protein ECT2"
FT /id="PRO_0000080938"
FT DOMAIN 171..260
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 266..354
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 452..641
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 675..794
FT /note="PH"
FT REGION 388..449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 857..884
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 378..382
FT /note="Nuclear localization signal"
FT MOTIF 401..405
FT /note="Nuclear localization signal"
FT COMPBIAS 413..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 861..884
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 359
FT /note="Phosphothreonine; by PKC/PRKCI"
FT /evidence="ECO:0000269|PubMed:21189248,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 367
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 373
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:16170345,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 444
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:16247472"
FT MOD_RES 716
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 842
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 846
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 861
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 866
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 611
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 44
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10579713,
FT ECO:0000303|PubMed:14587037, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_041976"
FT VAR_SEQ 71..101
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10579713,
FT ECO:0000303|PubMed:14587037, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_041977"
FT VAR_SEQ 886..914
FT /note="GIPSPSLVSLPSFFERRSHTLSRSTTHLI -> ITHSVSTSNVIGFTKHVYV
FT QRLNSTGGRSQYSWFQSVRHSAFRASFSEILEGNTDFSNFKKVLSKSSLTFVKN (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_041978"
FT VARIANT 15
FT /note="S -> T (in dbSNP:rs34703432)"
FT /id="VAR_047064"
FT VARIANT 833
FT /note="T -> P (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035975"
FT MUTAGEN 184
FT /note="T->A: Inhibits interaction with RACGAP1. Abolishes
FT targeting to the central spindle."
FT /evidence="ECO:0000269|PubMed:19468300,
FT ECO:0000269|PubMed:25068414"
FT MUTAGEN 226
FT /note="K->A: Inhibits interaction with RACGAP1. Abolishes
FT targeting to the central spindle."
FT /evidence="ECO:0000269|PubMed:19468300,
FT ECO:0000269|PubMed:25068414"
FT MUTAGEN 336
FT /note="W->R: Inhibits homodimerization. Increases binding
FT with RhoA and GEF activity."
FT /evidence="ECO:0000269|PubMed:15545273"
FT MUTAGEN 338
FT /note="W->A: 2-fold increase in GEF activity."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 359
FT /note="T->A: Inhibits its phosphorylation and anchorage-
FT independent growth and invasion in cancer cells. Does not
FT inhibit its GEF activity."
FT /evidence="ECO:0000269|PubMed:21189248"
FT MUTAGEN 373
FT /note="T->A: Does not inhibit its Rho exchange activity.
FT Increases interaction with RACGAP1. Does not inhibit
FT anchorage-independent growth and invasion in cancer cells."
FT /evidence="ECO:0000269|PubMed:16103226,
FT ECO:0000269|PubMed:16170345"
FT MUTAGEN 373
FT /note="T->D: Does not inhibit subcellular localization or
FT homodimerization. Enhances its Rho exchange activity."
FT /evidence="ECO:0000269|PubMed:16103226,
FT ECO:0000269|PubMed:16170345"
FT MUTAGEN 379..381
FT /note="KRR->AAA: Shows both nuclear and cytoplasmic
FT localization and activates its transforming activity."
FT /evidence="ECO:0000269|PubMed:14645260"
FT MUTAGEN 402..404
FT /note="RKR->AKA: Shows both nuclear and cytoplasmic
FT localization and activates its transforming activity."
FT /evidence="ECO:0000269|PubMed:14645260"
FT MUTAGEN 444
FT /note="T->A: Diminishes its phosphorylation status. Reduces
FT its interaction with PLK1 and Rho exchange activity. Does
FT not change its subcellular localization. Does not inhibit
FT anchorage-independent growth and invasion in cancer cells."
FT /evidence="ECO:0000269|PubMed:16247472"
FT MUTAGEN 444
FT /note="T->D: Does not reduce its interaction with PLK1,
FT change its subcellular localization and Rho exchange
FT activity."
FT /evidence="ECO:0000269|PubMed:16247472"
FT MUTAGEN 488
FT /note="R->C: Partially releases inhibition."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 570
FT /note="R->D: 2-fold increase in GEF activity."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 573
FT /note="A->D: 2-fold increase in GEF activity."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 586
FT /note="R->Q: Complete loss of GEF activity and failure to
FT support cytokinesis."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 596..599
FT /note="PVQR->AAAA: Inhibits activation of the transforming
FT activity."
FT /evidence="ECO:0000269|PubMed:14645260"
FT MUTAGEN 601
FT /note="P->S: Complete loss of GEF activity and failure to
FT support cytokinesis."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 652
FT /note="F->A: No effect on GEF activity but severely
FT decreases ECT2 activation by RHOA. Localizes correctly but
FT fails to rescue the cytokinesis defect caused by knockdown
FT of endogenous ECT2 in contrast to the wild-type protein
FT which rescues this defect."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 656
FT /note="Y->A: No effect on GEF activity but severely
FT decreases ECT2 activation by RHOA. Fails to rescue the
FT cytokinesis defect caused by knockdown of endogenous ECT2
FT in contrast to the wild-type protein which rescues this
FT defect."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 670
FT /note="R->Q: Marked increase in GEF activity and rescues
FT the cytokinesis defect caused by depletion of endogenous
FT ECT2. When expressed in a cancer cell line, causes faster
FT cell proliferation than the wild-type protein."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 734
FT /note="P->D: More than 10-fold increase in GEF activity.
FT Overexpression causes noticeable changes in interphase cell
FT morphology such as cell rounding and formation of stress
FT fibers, suggesting ectopic RhoA activation."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 796
FT /note="C->K: More than 10-fold increase in GEF activity.
FT Overexpression causes noticeable changes in interphase cell
FT morphology such as cell rounding and formation of stress
FT fibers, suggesting ectopic RHOA activation."
FT /evidence="ECO:0000269|PubMed:31888991"
FT MUTAGEN 846
FT /note="T->A: Diminishes its phosphorylation status."
FT /evidence="ECO:0000269|PubMed:16247472"
FT CONFLICT 66
FT /note="I -> T (in Ref. 5; BAB14498)"
FT /evidence="ECO:0000305"
FT CONFLICT 276
FT /note="L -> F (in Ref. 5; BAB14498)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="E -> D (in Ref. 5; BAB14498)"
FT /evidence="ECO:0000305"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:4N40"
FT HELIX 57..59
FT /evidence="ECO:0007829|PDB:4N40"
FT HELIX 63..70
FT /evidence="ECO:0007829|PDB:4N40"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:4N40"
FT HELIX 115..119
FT /evidence="ECO:0007829|PDB:4N40"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:4N40"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:4N40"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:4N40"
FT HELIX 151..159
FT /evidence="ECO:0007829|PDB:4N40"
FT TURN 173..178
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 189..201
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 215..224
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 225..233
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 241..249
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 260..263
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:6L30"
FT TURN 270..273
FT /evidence="ECO:0007829|PDB:3L46"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:3L46"
FT HELIX 283..295
FT /evidence="ECO:0007829|PDB:3L46"
FT STRAND 309..313
FT /evidence="ECO:0007829|PDB:3L46"
FT TURN 315..317
FT /evidence="ECO:0007829|PDB:3L46"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:3L46"
FT STRAND 330..333
FT /evidence="ECO:0007829|PDB:3L46"
FT HELIX 334..343
FT /evidence="ECO:0007829|PDB:3L46"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:3L46"
FT HELIX 453..477
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 479..483
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 495..502
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 505..522
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 532..552
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 554..567
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 569..579
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 582..584
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 589..611
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 622..634
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 635..637
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 642..657
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 664..667
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 672..687
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 691..697
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 700..706
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 726..734
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 735..737
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 738..744
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 748..758
FT /evidence="ECO:0007829|PDB:6L30"
FT TURN 761..763
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 767..773
FT /evidence="ECO:0007829|PDB:6L30"
FT HELIX 780..795
FT /evidence="ECO:0007829|PDB:6L30"
FT STRAND 803..807
FT /evidence="ECO:0007829|PDB:6L30"
SQ SEQUENCE 914 AA; 103505 MW; F40FC4F982FB8C78 CRC64;
MAENSVLTST TGRTSLADSS IFDSKVTEIS KENLLIGSTS YVEEEMPQIE TRVILVQEAG
KQEELIKALK TIKIMEVPVI KIKESCPGKS DEKLIKSVIN MDIKVGFVKM ESVEEFEGLD
SPEFENVFVV TDFQDSVFND LYKADCRVIG PPVVLNCSQK GEPLPFSCRP LYCTSMMNLV
LCFTGFRKKE ELVRLVTLVH HMGGVIRKDF NSKVTHLVAN CTQGEKFRVA VSLGTPIMKP
EWIYKAWERR NEQDFYAAVD DFRNEFKVPP FQDCILSFLG FSDEEKTNME EMTEMQGGKY
LPLGDERCTH LVVEENIVKD LPFEPSKKLY VVKQEWFWGS IQMDARAGET MYLYEKANTP
ELKKSVSMLS LNTPNSNRKR RRLKETLAQL SRETDVSPFP PRKRPSAEHS LSIGSLLDIS
NTPESSINYG DTPKSCTKSS KSSTPVPSKQ SARWQVAKEL YQTESNYVNI LATIIQLFQV
PLEEEGQRGG PILAPEEIKT IFGSIPDIFD VHTKIKDDLE DLIVNWDESK SIGDIFLKYS
KDLVKTYPPF VNFFEMSKET IIKCEKQKPR FHAFLKINQA KPECGRQSLV ELLIRPVQRL
PSVALLLNDL KKHTADENPD KSTLEKAIGS LKEVMTHINE DKRKTEAQKQ IFDVVYEVDG
CPANLLSSHR SLVQRVETIS LGEHPCDRGE QVTLFLFNDC LEIARKRHKV IGTFRSPHGQ
TRPPASLKHI HLMPLSQIKK VLDIRETEDC HNAFALLVRP PTEQANVLLS FQMTSDELPK
ENWLKMLCRH VANTICKADA ENLIYTADPE SFEVNTKDMD STLSRASRAI KKTSKKVTRA
FSFSKTPKRA LRRALMTSHG SVEGRSPSSN DKHVMSRLSS TSSLAGIPSP SLVSLPSFFE
RRSHTLSRST THLI
