SNAI1_HUMAN
ID SNAI1_HUMAN Reviewed; 264 AA.
AC O95863; B2R842; Q9P113; Q9UBP7; Q9UHH7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Zinc finger protein SNAI1;
DE AltName: Full=Protein snail homolog 1;
DE Short=Protein sna;
GN Name=SNAI1; Synonyms=SNAH;
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], AND VARIANT ALA-118.
RC TISSUE=Mammary gland;
RX PubMed=11245431;
RA Okubo T., Truong T.K., Yu B., Itoh T., Zhao J., Grube B., Zhou D., Chen S.;
RT "Down-regulation of promoter 1.3 activity of the human aromatase gene in
RT breast tissue by zinc-finger protein, snail (SnaH).";
RL Cancer Res. 61:1338-1346(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10543399; DOI=10.1007/s004399900143;
RA Twigg S.R., Wilkie A.O.M.;
RT "Characterisation of the human snail (SNAI1) gene and exclusion as a major
RT disease gene in craniosynostosis.";
RL Hum. Genet. 105:320-326(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10585766; DOI=10.1006/geno.1999.6010;
RA Paznekas W.A., Okajima K., Schertzer M., Wood S., Jabs E.W.;
RT "Genomic organization, expression, and chromosome location of the human
RT SNAIL gene (SNAI1) and a related processed pseudogene (SNAI1P).";
RL Genomics 62:42-49(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
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=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [MRNA] OF 1-172, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10655587; DOI=10.1038/35000034;
RA Batlle E., Sancho E., Franci C., Dominguez D., Monfar M., Baulida J.,
RA Garcia de Herreros A.;
RT "The transcription factor Snail is a repressor of E-cadherin gene
RT expression in epithelial tumour cells.";
RL Nat. Cell Biol. 2:84-89(2000).
RN [8]
RP INTERACTION WITH GSK3B AND BTRC, PHOSPHORYLATION AT SER-96; SER-100;
RP SER-104; SER-107; SER-111; SER-115 AND SER-119 BY GSK3B, UBIQUITINATION BY
RP BTRC, MUTAGENESIS OF SER-96; SER-100; SER-107; SER-111; SER-115 AND
RP SER-119, AND SUBCELLULAR LOCATION.
RX PubMed=15448698; DOI=10.1038/ncb1173;
RA Zhou B.P., Deng J., Xia W., Xu J., Li Y.M., Gunduz M., Hung M.C.;
RT "Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control
RT of epithelial-mesenchymal transition.";
RL Nat. Cell Biol. 6:931-940(2004).
RN [9]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-246 BY PAK1, AND MUTAGENESIS
RP OF SER-246.
RX PubMed=15833848; DOI=10.1158/0008-5472.can-04-3480;
RA Yang Z., Rayala S., Nguyen D., Vadlamudi R.K., Chen S., Kumar R.;
RT "Pak1 phosphorylation of snail, a master regulator of epithelial-to-
RT mesenchyme transition, modulates snail's subcellular localization and
RT functions.";
RL Cancer Res. 65:3179-3184(2005).
RN [10]
RP FUNCTION, INTERACTION WITH LOXL2 AND LOXL3, AND MUTAGENESIS OF LYS-9;
RP LYS-16; LYS-98 AND LYS-137.
RX PubMed=16096638; DOI=10.1038/sj.emboj.7600781;
RA Peinado H., Del Carmen Iglesias-de la Cruz M., Olmeda D., Csiszar K.,
RA Fong K.S., Vega S., Nieto M.A., Cano A., Portillo F.;
RT "A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and
RT tumor progression.";
RL EMBO J. 24:3446-3458(2005).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH KPNB1.
RX PubMed=15836774; DOI=10.1111/j.1365-2443.2005.00850.x;
RA Yamasaki H., Sekimoto T., Ohkubo T., Douchi T., Nagata Y., Ozawa M.,
RA Yoneda Y.;
RT "Zinc finger domain of Snail functions as a nuclear localization signal for
RT importin beta-mediated nuclear import pathway.";
RL Genes Cells 10:455-464(2005).
RN [12]
RP FUNCTION, INTERACTION WITH GSK3B AND BTRC, PHOSPHORYLATION AT SER-104 AND
RP SER-107, AND MUTAGENESIS OF SER-96; SER-104 AND SER-107.
RX PubMed=15647282; DOI=10.1074/jbc.m413878200;
RA Yook J.I., Li X.Y., Ota I., Fearon E.R., Weiss S.J.;
RT "Wnt-dependent regulation of the E-cadherin repressor snail.";
RL J. Biol. Chem. 280:11740-11748(2005).
RN [13]
RP INTERACTION WITH LIMD1 AND AJUBA.
RX PubMed=18331720; DOI=10.1016/j.devcel.2008.01.005;
RA Langer E.M., Feng Y., Zhaoyuan H., Rauscher F.J. III, Kroll K.L.,
RA Longmore G.D.;
RT "Ajuba LIM proteins are snail/slug corepressors required for neural crest
RT development in Xenopus.";
RL Dev. Cell 14:424-436(2008).
RN [14]
RP INTERACTION WITH KPNA2; KPNB1; TNPO1 AND IPO7, AND MUTAGENESIS OF
RP 151-ARG-LYS-152; CYS-156; LYS-161; LYS-170; CYS-182; LYS-187; ARG-191;
RP CYS-210; ARG-215; ARG-220; ASN-222; ARG-224; 232-ASP--LYS-235; CYS-238 AND
RP GLN-239.
RX PubMed=19386897; DOI=10.1242/jcs.041749;
RA Mingot J.M., Vega S., Maestro B., Sanz J.M., Nieto M.A.;
RT "Characterization of Snail nuclear import pathways as representatives of
RT C2H2 zinc finger transcription factors.";
RL J. Cell Sci. 122:1452-1460(2009).
RN [15]
RP FUNCTION, INTERACTION WITH KDM1A, SUBCELLULAR LOCATION, DOMAIN, AND
RP MUTAGENESIS OF PRO-2; ARG-3; SER-4; PHE-5; ARG-8 AND LYS-9.
RX PubMed=20389281; DOI=10.1038/emboj.2010.63;
RA Lin Y., Wu Y., Li J., Dong C., Ye X., Chi Y.I., Evers B.M., Zhou B.P.;
RT "The SNAG domain of Snail1 functions as a molecular hook for recruiting
RT lysine-specific demethylase 1.";
RL EMBO J. 29:1803-1816(2010).
RN [16]
RP GLYCOSYLATION AT SER-112.
RX PubMed=20959806; DOI=10.1038/emboj.2010.254;
RA Park S.Y., Kim H.S., Kim N.H., Ji S., Cha S.Y., Kang J.G., Ota I.,
RA Shimada K., Konishi N., Nam H.W., Hong S.W., Yang W.H., Roth J., Yook J.I.,
RA Cho J.W.;
RT "Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic
RT condition.";
RL EMBO J. 29:3787-3796(2010).
RN [17]
RP FUNCTION, INTERACTION WITH EGR1, AND INDUCTION.
RX PubMed=20121949; DOI=10.1111/j.1742-4658.2009.07553.x;
RA Hu C.T., Chang T.Y., Cheng C.C., Liu C.S., Wu J.R., Li M.C., Wu W.S.;
RT "Snail associates with EGR-1 and SP-1 to upregulate transcriptional
RT activation of p15INK4b.";
RL FEBS J. 277:1202-1218(2010).
RN [18]
RP INTERACTION WITH TP53 AND MDM2, AND UBIQUITINATION BY MDM2.
RX PubMed=20385133; DOI=10.1016/j.febslet.2010.04.006;
RA Lim S.O., Kim H., Jung G.;
RT "p53 inhibits tumor cell invasion via the degradation of snail protein in
RT hepatocellular carcinoma.";
RL FEBS Lett. 584:2231-2236(2010).
RN [19]
RP UBIQUITINATION BY FBXL14 AND BTRC, INTERACTION WITH FBXL14, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LYS-98; LYS-137 AND LYS-146.
RX PubMed=19955572; DOI=10.1074/jbc.m109.065995;
RA Vinas-Castells R., Beltran M., Valls G., Gomez I., Garcia J.M.,
RA Montserrat-Sentis B., Baulida J., Bonilla F., de Herreros A.G., Diaz V.M.;
RT "The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for
RT proteasome degradation.";
RL J. Biol. Chem. 285:3794-3805(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH CSNK2A1,
RP PHOSPHORYLATION AT SER-11; SER-82; SER-92; SER-104 AND SER-107, AND
RP MUTAGENESIS OF SER-11; SER-92; SER-104 AND SER-107.
RX PubMed=19923321; DOI=10.1091/mbc.e09-06-0504;
RA MacPherson M.R., Molina P., Souchelnytskyi S., Wernstedt C.,
RA Martin-Perez J., Portillo F., Cano A.;
RT "Phosphorylation of serine 11 and serine 92 as new positive regulators of
RT human Snail1 function: potential involvement of casein kinase-2 and the
RT cAMP-activated kinase protein kinase A.";
RL Mol. Biol. Cell 21:244-253(2010).
RN [21]
RP INTERACTION WITH CSNK1E, PHOSPHORYLATION BY CSNK1E AND GSK3B,
RP PHOSPHORYLATION AT SER-96, AND MUTAGENESIS OF SER-96; SER-100; SER-104 AND
RP SER-107.
RX PubMed=20305697; DOI=10.1038/onc.2010.77;
RA Xu Y., Lee S.H., Kim H.S., Kim N.H., Piao S., Park S.H., Jung Y.S.,
RA Yook J.I., Park B.J., Ha N.C.;
RT "Role of CK1 in GSK3beta-mediated phosphorylation and degradation of
RT snail.";
RL Oncogene 29:3124-3133(2010).
RN [22]
RP FUNCTION, INTERACTION WITH KDM1A, AND MUTAGENESIS OF PRO-2.
RX PubMed=20562920; DOI=10.1038/onc.2010.234;
RA Lin T., Ponn A., Hu X., Law B.K., Lu J.;
RT "Requirement of the histone demethylase LSD1 in Snai1-mediated
RT transcriptional repression during epithelial-mesenchymal transition.";
RL Oncogene 29:4896-4904(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH NOTCH1 AND MDM2,
RP SUBCELLULAR LOCATION, UBIQUITINATION BY MDM2, AND MUTAGENESIS OF SER-96 AND
RP SER-100.
RX PubMed=22128911; DOI=10.1186/1741-7007-9-83;
RA Lim S.O., Kim H.S., Quan X., Ahn S.M., Kim H., Hsieh D., Seong J.K.,
RA Jung G.;
RT "Notch1 binds and induces degradation of Snail in hepatocellular
RT carcinoma.";
RL BMC Biol. 9:83-83(2011).
RN [24]
RP INTERACTION WITH KPNB1; KPNA1; KPNA4 AND KPNA2.
RX PubMed=21454664; DOI=10.1074/jbc.m110.213579;
RA Sekimoto T., Miyamoto Y., Arai S., Yoneda Y.;
RT "Importin alpha protein acts as a negative regulator for Snail protein
RT nuclear import.";
RL J. Biol. Chem. 286:15126-15131(2011).
RN [25]
RP INTERACTION WITH PARP1, SUBCELLULAR LOCATION, AND ADP-RIBOSYLATION BY
RP PARP1.
RX PubMed=21577210; DOI=10.1038/onc.2011.153;
RA Rodriguez M.I., Gonzalez-Flores A., Dantzer F., Collard J.,
RA de Herreros A.G., Oliver F.J.;
RT "Poly(ADP-ribose)-dependent regulation of Snail1 protein stability.";
RL Oncogene 30:4365-4372(2011).
RN [26]
RP IDENTIFICATION BY 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 [27]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION AT THR-203 BY LATS2, AND MUTAGENESIS OF THR-203.
RX PubMed=21952048; DOI=10.1038/emboj.2011.357;
RA Zhang K., Rodriguez-Aznar E., Yabuta N., Owen R.J., Mingot J.M., Nojima H.,
RA Nieto M.A., Longmore G.D.;
RT "Lats2 kinase potentiates Snail1 activity by promoting nuclear retention
RT upon phosphorylation.";
RL EMBO J. 31:29-43(2012).
RN [28]
RP SUBCELLULAR LOCATION.
RX PubMed=25893292; DOI=10.1038/onc.2015.100;
RA Hwangbo C., Tae N., Lee S., Kim O., Park O.K., Kim J., Kwon S.H., Lee J.H.;
RT "Syntenin regulates TGF-beta1-induced Smad activation and the epithelial-
RT to-mesenchymal transition by inhibiting caveolin-mediated TGF-beta type I
RT receptor internalization.";
RL Oncogene 35:389-401(2016).
RN [29] {ECO:0007744|PDB:2Y48}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 2-21 IN COMPLEX WITH KDM1A,
RP INTERACTION WITH KDM1A, DOMAIN, AND FUNCTION.
RX PubMed=21300290; DOI=10.1016/j.str.2011.01.001;
RA Baron R., Binda C., Tortorici M., McCammon J.A., Mattevi A.;
RT "Molecular mimicry and ligand recognition in binding and catalysis by the
RT histone demethylase LSD1-CoREST complex.";
RL Structure 19:212-220(2011).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH ZINC AND KPNB1,
RP INTERACTION WITH KPNB1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-191;
RP TRP-193; GLN-196; ARG-224; GLN-228 AND ARG-247.
RX PubMed=24699649; DOI=10.1107/s1399004714000972;
RA Choi S., Yamashita E., Yasuhara N., Song J., Son S.Y., Won Y.H., Hong H.R.,
RA Shin Y.S., Sekimoto T., Park I.Y., Yoneda Y., Lee S.J.;
RT "Structural basis for the selective nuclear import of the C2H2 zinc-finger
RT protein Snail by importin beta.";
RL Acta Crystallogr. D 70:1050-1060(2014).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 2-7 IN COMPLEX WITH KDM1A,
RP INTERACTION WITH KDM1A, AND FUNCTION.
RX PubMed=23721412; DOI=10.1021/cb4001926;
RA Tortorici M., Borrello M.T., Tardugno M., Chiarelli L.R., Pilotto S.,
RA Ciossani G., Vellore N.A., Bailey S.G., Cowan J., O'Connell M., Crabb S.J.,
RA Packham G., Mai A., Baron R., Ganesan A., Mattevi A.;
RT "Protein recognition by short peptide reversible inhibitors of the
RT chromatin-modifying LSD1/CoREST lysine demethylase.";
RL ACS Chem. Biol. 8:1677-1682(2013).
CC -!- FUNCTION: Involved in induction of the epithelial to mesenchymal
CC transition (EMT), formation and maintenance of embryonic mesoderm,
CC growth arrest, survival and cell migration. Binds to 3 E-boxes of the
CC E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8
CC and, in association with histone demethylase KDM1A which it recruits to
CC the promoters, causes a decrease in dimethylated H3K4 levels and
CC represses transcription (PubMed:20389281, PubMed:20562920). The N-
CC terminal SNAG domain competes with histone H3 for the same binding site
CC on the histone demethylase complex formed by KDM1A and RCOR1, and
CC thereby inhibits demethylation of histone H3 at 'Lys-4' (in vitro)
CC (PubMed:20389281, PubMed:21300290, PubMed:23721412). During EMT,
CC involved with LOXL2 in negatively regulating pericentromeric
CC heterochromatin transcription (By similarity). SNAI1 recruits LOXL2 to
CC pericentromeric regions to oxidize histone H3 and repress transcription
CC which leads to release of heterochromatin component CBX5/HP1A, enabling
CC chromatin reorganization and acquisition of mesenchymal traits (By
CC similarity). Associates with EGR1 and SP1 to mediate tetradecanoyl
CC phorbol acetate (TPA)-induced up-regulation of CDKN2B, possibly by
CC binding to the CDKN2B promoter region 5'-TCACA-3. In addition, may also
CC activate the CDKN2B promoter by itself. {ECO:0000250|UniProtKB:Q02085,
CC ECO:0000269|PubMed:10655587, ECO:0000269|PubMed:15647282,
CC ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:20121949,
CC ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:20562920,
CC ECO:0000269|PubMed:21300290, ECO:0000269|PubMed:21952048,
CC ECO:0000269|PubMed:23721412}.
CC -!- SUBUNIT: Interacts with FBXL14 and GSK3B. Interacts with BTRC;
CC interaction occurs when it is phosphorylated on the destruction motif.
CC Interacts (via SNAG domain) with WTIP (via LIM domains) (By
CC similarity). Interacts (via SNAG domain) with LIMD1 (via LIM domains),
CC and AJUBA (via LIM domains). Interacts with LOXL2 and LOXL3. Interacts
CC (via N-terminal region) with CSNK2A1. Interacts with EGR1 upon TPA
CC induction. Interacts (via N-terminal region) with LATS2; the
CC interaction is dependent on LATS2 kinase activity but independent of
CC SNAI1 Thr-203 phosphorylation. Interacts (via zinc fingers) with KPNB1
CC and TNPO1; the interactions mediate nuclear import. Interacts (via zinc
CC fingers) with KPNA1; the interaction disrupts the transport complex
CC with KPNB1 and prevents nuclear import increasing SNAI1 degradation in
CC the cytoplasm. Interacts (via zinc fingers) with KPNA2; the
CC interaction, in combination with KPNB1, mediates nuclear import.
CC Interacts with KPNA4; this interaction mediates nuclear import. May
CC interact (via zinc fingers) with IPO7. Interacts (via zinc fingers)
CC with PARP1; the interaction requires SNAI1 to be poly-ADP-ribosylated
CC and non-phosphorylated (active) by GSK3B. Interacts (via SNAG domain)
CC with KDM1A (PubMed:20389281, PubMed:20562920, PubMed:21300290,
CC PubMed:23721412). Interaction with KDM1A is necessary for the down-
CC regulation of dimethylated H3K4 mark and promoter activity of E-
CC cadherin/CDH1, CDN7 and KRT8 (PubMed:20389281, PubMed:20562920).
CC Interacts with TP53/p53 and (via zinc fingers) with NOTCH1 (via
CC intracellular domain); the interactions induce SNAI1 degradation via
CC MDM2-mediated ubiquitination and inhibit SNAI1-induced cell invasion.
CC Interacts with MDM2; the interaction promotes SNAI1 ubiquitination.
CC Interacts (via zinc fingers) with CSNK1E. Interacts with PAK1
CC (PubMed:15833848). {ECO:0000250, ECO:0000269|PubMed:15448698,
CC ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:15833848,
CC ECO:0000269|PubMed:15836774, ECO:0000269|PubMed:16096638,
CC ECO:0000269|PubMed:18331720, ECO:0000269|PubMed:19386897,
CC ECO:0000269|PubMed:19923321, ECO:0000269|PubMed:19955572,
CC ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:20305697,
CC ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20389281,
CC ECO:0000269|PubMed:20562920, ECO:0000269|PubMed:21300290,
CC ECO:0000269|PubMed:21454664, ECO:0000269|PubMed:21577210,
CC ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:23721412,
CC ECO:0000269|PubMed:24699649}.
CC -!- INTERACTION:
CC O95863; P35609: ACTN2; NbExp=7; IntAct=EBI-1045459, EBI-77797;
CC O95863; Q08043: ACTN3; NbExp=3; IntAct=EBI-1045459, EBI-2880652;
CC O95863; Q96IF1: AJUBA; NbExp=3; IntAct=EBI-1045459, EBI-949782;
CC O95863; Q9Y297: BTRC; NbExp=2; IntAct=EBI-1045459, EBI-307461;
CC O95863; Q9Y2V7: COG6; NbExp=3; IntAct=EBI-1045459, EBI-3866319;
CC O95863; Q5JVL4: EFHC1; NbExp=3; IntAct=EBI-1045459, EBI-743105;
CC O95863; Q09472: EP300; NbExp=3; IntAct=EBI-1045459, EBI-447295;
CC O95863; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-1045459, EBI-371922;
CC O95863; Q8N1E6: FBXL14; NbExp=2; IntAct=EBI-1045459, EBI-6425532;
CC O95863; Q86XK2: FBXO11; NbExp=6; IntAct=EBI-1045459, EBI-1047804;
CC O95863; Q14192: FHL2; NbExp=3; IntAct=EBI-1045459, EBI-701903;
CC O95863; Q92990: GLMN; NbExp=3; IntAct=EBI-1045459, EBI-726150;
CC O95863; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-1045459, EBI-5916454;
CC O95863; P49841: GSK3B; NbExp=5; IntAct=EBI-1045459, EBI-373586;
CC O95863; Q13547: HDAC1; NbExp=3; IntAct=EBI-1045459, EBI-301834;
CC O95863; Q92769: HDAC2; NbExp=2; IntAct=EBI-1045459, EBI-301821;
CC O95863; O60341: KDM1A; NbExp=32; IntAct=EBI-1045459, EBI-710124;
CC O95863; Q15323: KRT31; NbExp=4; IntAct=EBI-1045459, EBI-948001;
CC O95863; Q6A162: KRT40; NbExp=4; IntAct=EBI-1045459, EBI-10171697;
CC O95863; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-1045459, EBI-11959885;
CC O95863; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-1045459, EBI-10172526;
CC O95863; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-1045459, EBI-742948;
CC O95863; Q7Z3S9: NOTCH2NLA; NbExp=4; IntAct=EBI-1045459, EBI-945833;
CC O95863; P09874: PARP1; NbExp=10; IntAct=EBI-1045459, EBI-355676;
CC O95863; Q99471: PFDN5; NbExp=3; IntAct=EBI-1045459, EBI-357275;
CC O95863; Q04206: RELA; NbExp=5; IntAct=EBI-1045459, EBI-73886;
CC O95863; O14543: SOCS3; NbExp=3; IntAct=EBI-1045459, EBI-714146;
CC O95863; Q96BD6: SPSB1; NbExp=3; IntAct=EBI-1045459, EBI-2659201;
CC O95863; P04637: TP53; NbExp=2; IntAct=EBI-1045459, EBI-366083;
CC O95863; Q12933: TRAF2; NbExp=3; IntAct=EBI-1045459, EBI-355744;
CC O95863; P36406: TRIM23; NbExp=7; IntAct=EBI-1045459, EBI-740098;
CC O95863; Q9C035: TRIM5; NbExp=3; IntAct=EBI-1045459, EBI-924214;
CC O95863; Q15654: TRIP6; NbExp=4; IntAct=EBI-1045459, EBI-742327;
CC O95863; P45481: Crebbp; Xeno; NbExp=7; IntAct=EBI-1045459, EBI-296306;
CC O95863; P63085: Mapk1; Xeno; NbExp=3; IntAct=EBI-1045459, EBI-397697;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15448698,
CC ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:20389281,
CC ECO:0000269|PubMed:24699649, ECO:0000269|PubMed:25893292}. Cytoplasm
CC {ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15833848}. Note=Once
CC phosphorylated (probably on Ser-107, Ser-111, Ser-115 and Ser-119) it
CC is exported from the nucleus to the cytoplasm where subsequent
CC phosphorylation of the destruction motif and ubiquitination involving
CC BTRC occurs. {ECO:0000269|PubMed:15448698}.
CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues with the highest
CC expression in kidney. Expressed in mesenchymal and epithelial cell
CC lines. {ECO:0000269|PubMed:10655587}.
CC -!- INDUCTION: Induced by TPA maximally by 2.5-fold at 4 hours, in HepG2
CC cells (at protein level). {ECO:0000269|PubMed:20121949}.
CC -!- PTM: Phosphorylated by GSK3B. Once phosphorylated, it becomes a target
CC for BTRC ubiquitination. Phosphorylation by CSNK1E, probably at Ser-
CC 104, provides the priming site for the subsequent phosphorylation by
CC GSK3B, probably at Ser-100 and Ser-96. Phosphorylation by PAK1 may
CC modulate its transcriptional activity by promoting increased
CC accumulation in the nucleus. Phosphorylation at Ser-11 and Ser-92
CC positively regulates its functions in induction of EMT and cell
CC survival, respectively. Phosphorylation by LATS2, upon mitotic stress,
CC oncogenic stress or Hippo pathway activation, occurs in the nucleus and
CC promotes nuclear retention and stabilization of total cellular protein
CC level. {ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:19923321,
CC ECO:0000269|PubMed:20305697, ECO:0000305|PubMed:15448698}.
CC -!- PTM: Ubiquitinated on Lys-98, Lys-137 and Lys-146 by FBXL14 and BTRC
CC leading to degradation. BTRC-triggered ubiquitination requires previous
CC GSK3B-mediated SNAI1 phosphorylation. Ubiquitination induced upon
CC interaction with NOTCH1 or TP53/p53 is mediated by MDM2.
CC -!- PTM: O-GlcNAcylation at Ser-112 is enhanced in hyperglycaemic
CC conditions, it opposes phosphorylation by GSK3B, and stabilizes the
CC protein.
CC -!- PTM: ADP-ribosylation by PARP1 increases protein half-life and may be
CC involved in TGFB-induced SNAI1 up-regulation.
CC -!- SIMILARITY: Belongs to the snail C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
CC -!- CAUTION: The interaction with mouse KPNA2 may prevent SNAI1 nuclear
CC import. {ECO:0000305|PubMed:21454664}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SNAI1ID452ch20q13.html";
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DR EMBL; AF125377; AAD17332.1; -; mRNA.
DR EMBL; AJ245657; CAB52414.1; -; Genomic_DNA.
DR EMBL; AJ245658; CAB52414.1; JOINED; Genomic_DNA.
DR EMBL; AJ245659; CAB52414.1; JOINED; Genomic_DNA.
DR EMBL; AF155233; AAD52986.1; -; Genomic_DNA.
DR EMBL; AF177731; AAD52996.1; -; Genomic_DNA.
DR EMBL; AK313228; BAG36039.1; -; mRNA.
DR EMBL; AL121712; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012910; AAH12910.1; -; mRNA.
DR EMBL; AF131208; AAF32527.1; -; mRNA.
DR CCDS; CCDS13423.1; -.
DR RefSeq; NP_005976.2; NM_005985.3.
DR PDB; 2Y48; X-ray; 3.00 A; C=2-21.
DR PDB; 3W5K; X-ray; 2.60 A; B=1-264.
DR PDB; 3ZMT; X-ray; 3.10 A; C=2-7.
DR PDB; 4QLI; X-ray; 1.45 A; B=175-180.
DR PDBsum; 2Y48; -.
DR PDBsum; 3W5K; -.
DR PDBsum; 3ZMT; -.
DR PDBsum; 4QLI; -.
DR AlphaFoldDB; O95863; -.
DR SMR; O95863; -.
DR BioGRID; 112499; 519.
DR CORUM; O95863; -.
DR DIP; DIP-50870N; -.
DR IntAct; O95863; 70.
DR MINT; O95863; -.
DR STRING; 9606.ENSP00000244050; -.
DR GlyGen; O95863; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95863; -.
DR PhosphoSitePlus; O95863; -.
DR SwissPalm; O95863; -.
DR BioMuta; SNAI1; -.
DR EPD; O95863; -.
DR jPOST; O95863; -.
DR MassIVE; O95863; -.
DR PaxDb; O95863; -.
DR PeptideAtlas; O95863; -.
DR PRIDE; O95863; -.
DR ProteomicsDB; 51096; -.
DR Antibodypedia; 3135; 916 antibodies from 46 providers.
DR CPTC; O95863; 1 antibody.
DR DNASU; 6615; -.
DR Ensembl; ENST00000244050.3; ENSP00000244050.2; ENSG00000124216.4.
DR GeneID; 6615; -.
DR KEGG; hsa:6615; -.
DR MANE-Select; ENST00000244050.3; ENSP00000244050.2; NM_005985.4; NP_005976.2.
DR UCSC; uc002xuz.4; human.
DR CTD; 6615; -.
DR DisGeNET; 6615; -.
DR GeneCards; SNAI1; -.
DR HGNC; HGNC:11128; SNAI1.
DR HPA; ENSG00000124216; Low tissue specificity.
DR MIM; 604238; gene.
DR neXtProt; NX_O95863; -.
DR OpenTargets; ENSG00000124216; -.
DR PharmGKB; PA35977; -.
DR VEuPathDB; HostDB:ENSG00000124216; -.
DR eggNOG; KOG2462; Eukaryota.
DR GeneTree; ENSGT00940000154681; -.
DR HOGENOM; CLU_002678_42_3_1; -.
DR InParanoid; O95863; -.
DR OMA; GWASFRP; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; O95863; -.
DR TreeFam; TF315515; -.
DR PathwayCommons; O95863; -.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR SignaLink; O95863; -.
DR SIGNOR; O95863; -.
DR BioGRID-ORCS; 6615; 21 hits in 1098 CRISPR screens.
DR EvolutionaryTrace; O95863; -.
DR GeneWiki; SNAI1; -.
DR GenomeRNAi; 6615; -.
DR Pharos; O95863; Tbio.
DR PRO; PR:O95863; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; O95863; protein.
DR Bgee; ENSG00000124216; Expressed in omental fat pad and 100 other tissues.
DR Genevisible; O95863; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005721; C:pericentric heterochromatin; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0070888; F:E-box binding; IDA:BHF-UCL.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0003180; P:aortic valve morphogenesis; TAS:BHF-UCL.
DR GO; GO:0060536; P:cartilage morphogenesis; IEA:Ensembl.
DR GO; GO:0010631; P:epithelial cell migration; IEA:Ensembl.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:UniProtKB.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0070828; P:heterochromatin organization; ISS:UniProtKB.
DR GO; GO:0060972; P:left/right pattern formation; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; ISS:UniProtKB.
DR GO; GO:0060806; P:negative regulation of cell differentiation involved in embryonic placenta development; IEA:Ensembl.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IMP:BHF-UCL.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0010957; P:negative regulation of vitamin D biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0061314; P:Notch signaling involved in heart development; ISS:BHF-UCL.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; IMP:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; IEA:Ensembl.
DR IDEAL; IID00363; -.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 2.
DR SMART; SM00355; ZnF_C2H2; 4.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Cytoplasm; Developmental protein;
KW DNA-binding; Glycoprotein; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..264
FT /note="Zinc finger protein SNAI1"
FT /id="PRO_0000047029"
FT ZN_FING 154..176
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 178..202
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 208..230
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 236..259
FT /note="C2H2-type 4; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..20
FT /note="SNAG domain"
FT /evidence="ECO:0000305|PubMed:20389281,
FT ECO:0000305|PubMed:21300290"
FT REGION 2..7
FT /note="Required and sufficient for interaction with KDM1A"
FT /evidence="ECO:0000269|PubMed:20389281,
FT ECO:0000269|PubMed:23721412"
FT REGION 10..40
FT /note="LATS2 binding"
FT REGION 86..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 120..151
FT /note="Required for FBXL14-triggered degradation"
FT REGION 151..264
FT /note="Required for nuclear localization and interaction
FT with KPNB1, NOTCH1 and PARP1"
FT /evidence="ECO:0000269|PubMed:21577210,
FT ECO:0000269|PubMed:22128911"
FT MOTIF 95..100
FT /note="Destruction motif"
FT COMPBIAS 86..100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 11
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:19923321"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19923321"
FT MOD_RES 92
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:19923321"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20305697,
FT ECO:0000305|PubMed:15448698"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15448698"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15647282,
FT ECO:0000269|PubMed:19923321, ECO:0000305|PubMed:15448698"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15647282,
FT ECO:0000269|PubMed:19923321, ECO:0000305|PubMed:15448698"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15448698"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15448698"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15448698"
FT MOD_RES 203
FT /note="Phosphothreonine; by LATS2"
FT /evidence="ECO:0000269|PubMed:21952048"
FT MOD_RES 246
FT /note="Phosphoserine; by PAK1"
FT /evidence="ECO:0000269|PubMed:15833848"
FT CARBOHYD 112
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:20959806"
FT CROSSLNK 98
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT CROSSLNK 137
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT CROSSLNK 146
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT VARIANT 66
FT /note="A -> V (in dbSNP:rs34261470)"
FT /id="VAR_069162"
FT VARIANT 118
FT /note="V -> A (in dbSNP:rs4647958)"
FT /evidence="ECO:0000269|PubMed:11245431"
FT /id="VAR_019969"
FT MUTAGEN 2
FT /note="P->A: Abolishes repressor activity on E-
FT cadherin/CDH1 promoter and binding to KDM1A."
FT /evidence="ECO:0000269|PubMed:20389281,
FT ECO:0000269|PubMed:20562920"
FT MUTAGEN 3
FT /note="R->A: Loss of interaction with KDM1A."
FT /evidence="ECO:0000269|PubMed:20389281"
FT MUTAGEN 4
FT /note="S->A: Loss of interaction with KDM1A."
FT /evidence="ECO:0000269|PubMed:20389281"
FT MUTAGEN 5
FT /note="F->A: Loss of interaction with KDM1A."
FT /evidence="ECO:0000269|PubMed:20389281"
FT MUTAGEN 8
FT /note="R->A: Loss of interaction with KDM1A."
FT /evidence="ECO:0000269|PubMed:20389281"
FT MUTAGEN 9
FT /note="K->A: Loss of interaction with KDM1A."
FT /evidence="ECO:0000269|PubMed:20389281"
FT MUTAGEN 9
FT /note="K->R: Does not affect E-cadherin/CDH1 repression;
FT when associated with R-16."
FT /evidence="ECO:0000269|PubMed:16096638"
FT MUTAGEN 11
FT /note="S->A: Abolishes PKA phosphorylation. Strongly
FT decreases repressor activity on E-cadherin/CDH1 and CLDN1
FT promoters. Increases protein stability. Affects function in
FT EMT."
FT /evidence="ECO:0000269|PubMed:19923321"
FT MUTAGEN 16
FT /note="K->R: Does not affect E-cadherin repression; when
FT associated with R-9."
FT /evidence="ECO:0000269|PubMed:16096638"
FT MUTAGEN 92
FT /note="S->A: Abolishes CK2 phosphorylation. Strongly
FT decreases repressor activity on E-cadherin/CDH1 and CLDN1
FT promoters. Increases protein stability. Affects function in
FT cell survival. Abolishes phosphorylation in the serine-rich
FT region; when associated with A-104 and A-107."
FT /evidence="ECO:0000269|PubMed:19923321"
FT MUTAGEN 92
FT /note="S->E: Does not affect repressor activity on E-
FT cadherin/CDH1 promoter."
FT /evidence="ECO:0000269|PubMed:19923321"
FT MUTAGEN 96
FT /note="S->A: Abolishes recognition and ubiquitination by
FT BTRC which increases steady state level and half-life.
FT Preferentially localizes to the nucleus. Induces a more
FT aggressive tissue invasion program. Lower sensitivity to
FT BTRC-triggered degradation, impairs phosphorylation by
FT GSK3B and does not affect NOTCH1-induced degradation; when
FT associated with A-100. Lower sensitivity to BTRC-triggered
FT degradation, impaired phosphorylation by GSK3B and loss of
FT cytoplasmic localization; when associated with A-100; A-
FT 107; A-111; A-115 and A-119."
FT /evidence="ECO:0000269|PubMed:15448698,
FT ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:20305697,
FT ECO:0000269|PubMed:22128911"
FT MUTAGEN 98
FT /note="K->R: No change. Complete loss of sensitivity to
FT FBXL14- and BTRC-triggered degradation and loss of ability
FT to repress E-cadherin/CDH1; when associated with R-137 and
FT R-146."
FT /evidence="ECO:0000269|PubMed:16096638,
FT ECO:0000269|PubMed:19955572"
FT MUTAGEN 100
FT /note="S->A: Lower sensitivity to BTRC-triggered
FT degradation and impaired phosphorylation by GSK3B; when
FT associated with A-96. Lower sensitivity to BTRC-triggered
FT degradation, impaired phosphorylation by GSK3B and loss of
FT cytoplasmic localization; when associated with A-96; A-107;
FT A-111; A-115 and A-119. Does not affect NOTCH1-induced
FT degradation; when associated with A-96. Abolishes
FT phosphorylation at S-96."
FT /evidence="ECO:0000269|PubMed:15448698,
FT ECO:0000269|PubMed:20305697, ECO:0000269|PubMed:22128911"
FT MUTAGEN 104
FT /note="S->A: Increases protein stability, does not affect
FT repressor activity on E-cadherin/CDH1 promoter,
FT preferentially localizes to the nucleus, induces a more
FT aggressive tissue invasion program and impairs
FT phosphorylation by GSK3B, binding to BTRC and
FT ubiquitination; when associated with A-107. Impairs
FT phosphorylation in the serine-rich domain/region; when
FT associated with A-92 and A-107. Abolishes phosphorylation
FT at S-96."
FT /evidence="ECO:0000269|PubMed:15647282,
FT ECO:0000269|PubMed:19923321, ECO:0000269|PubMed:20305697"
FT MUTAGEN 107
FT /note="S->A: Lower sensitivity to BTRC-triggered
FT degradation, impaired phosphorylation by GSK3B and loss of
FT cytoplasmic localization; when associated with A-111; A-115
FT and A-119. Lower sensitivity to BTRC-triggered degradation,
FT impaired phosphorylation by GSK3B and loss of cytoplasmic
FT localization; when associated with A-96; A-100; A-111; A-
FT 115 and A-119. Increases protein stability, does not affect
FT repressor activity on E-cadherin promoter, preferentially
FT localizes to the nucleus, induces a more aggressive tissue
FT invasion program and impairs phosphorylation by GSK3B,
FT binding to BTRC and ubiquitination; when associated with A-
FT 104. Impairs phosphorylation in the serine-rich region;
FT when associated with A-92 and A-104. Abolishes
FT phosphorylation at S-96."
FT /evidence="ECO:0000269|PubMed:15448698,
FT ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:19923321,
FT ECO:0000269|PubMed:20305697"
FT MUTAGEN 107
FT /note="S->E: Predominantly localized to the cytoplasm; when
FT associated with E-111; E-115 and E-119."
FT /evidence="ECO:0000269|PubMed:15448698,
FT ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:19923321,
FT ECO:0000269|PubMed:20305697"
FT MUTAGEN 111
FT /note="S->A: Lower sensitivity to BTRC-triggered
FT degradation, impaired phosphorylation by GSK3B and loss of
FT cytoplasmic localization; when associated with A-107; A-115
FT and A-119. Lower sensitivity to BTRC-triggered degradation,
FT impaired phosphorylation by GSK3B and loss of cytoplasmic
FT localization; when associated with A-96; A-100; A-107; A-
FT 115 and A-119."
FT /evidence="ECO:0000269|PubMed:15448698"
FT MUTAGEN 111
FT /note="S->E: Predominantly localized to the cytoplasm; when
FT associated with E-107; E-115 and E-119."
FT /evidence="ECO:0000269|PubMed:15448698"
FT MUTAGEN 115
FT /note="S->A: Lower sensitivity to BTRC-triggered
FT degradation, impaired phosphorylation by GSK3B and loss of
FT cytoplasmic localization; when associated with A-107; A-111
FT and A-119. Lower sensitivity to BTRC-triggered degradation,
FT impaired phosphorylation by GSK3B and loss of cytoplasmic
FT localization; when associated with A-96; A-100; A-107; A-
FT 111 and A-119."
FT /evidence="ECO:0000269|PubMed:15448698"
FT MUTAGEN 115
FT /note="S->E: Predominantly localized to the cytoplasm; when
FT associated with E-107; E-111 and E-119."
FT /evidence="ECO:0000269|PubMed:15448698"
FT MUTAGEN 119
FT /note="S->A: Lower sensitivity to BTRC-triggered
FT degradation, impaired phosphorylation by GSK3B and loss of
FT cytoplasmic localization; when associated with A-107; A-111
FT and A-119. Lower sensitivity to BTRC-triggered degradation,
FT impaired phosphorylation by GSK3B and loss of cytoplasmic
FT localization; when associated with A-96; A-100; A-107; A-
FT 111 and A-115."
FT /evidence="ECO:0000269|PubMed:15448698"
FT MUTAGEN 119
FT /note="S->E: Predominantly localized to the cytoplasm; when
FT associated with E-107; E-111 and E-115."
FT /evidence="ECO:0000269|PubMed:15448698"
FT MUTAGEN 137
FT /note="K->R: Lower sensitivity to FBXL14-triggered
FT degradation. Lower sensitivity to FBXL14-triggered
FT degradation; when associated with R-146. Complete loss of
FT sensitivity to FBXL14- and BTRC-triggered degradation and
FT loss of ability to repress E-cadherin; when associated with
FT R-98 and R-146."
FT /evidence="ECO:0000269|PubMed:16096638,
FT ECO:0000269|PubMed:19955572"
FT MUTAGEN 146
FT /note="K->R: Lower sensitivity to FBXL14-triggered
FT degradation. Lower sensitivity to FBXL14-triggered
FT degradation; when associated with R-137. Complete loss of
FT sensitivity to FBXL14- and BTRC-triggered degradation; when
FT associated with R-98 and R-137."
FT /evidence="ECO:0000269|PubMed:19955572"
FT MUTAGEN 151..152
FT /note="RK->EE: Does not affect binding to KPNB1, KPNA2,
FT IPO7 or TNPO1."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 156
FT /note="C->A: Abolishes binding to KPNB1, KPNA2, IPO7 and
FT TNPO1 and nuclear localization."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 161
FT /note="K->E: Does not affect binding to KPNB1, KPNA2, IPO7
FT or TNPO1. No change in subcellular localization. Impairs
FT binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes
FT nuclear localization, DNA binding and repressor activity on
FT E-cadherin/CDH1 promoter; when associated with E-170.
FT Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and
FT nuclear localization; when associated with E-187 and/or E-
FT 220."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 170
FT /note="K->E: Does not affect binding to KPNB1, KPNA2, IPO7
FT or TNPO1. No change in subcellular localization. Impairs
FT binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes
FT nuclear localization, DNA binding and repressor activity on
FT E-cadherin/CDH1 promoter; when associated with E-161."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 182
FT /note="C->A: Impairs binding to KPNB1, IPO7 and TNPO1 and
FT abolishes binding to KPNA2. Localizes to cytoplasm and
FT nucleus."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 187
FT /note="K->E: Does not affect binding to KPNB1, KPNA2, IPO7
FT or TNPO1. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1
FT and abolishes nuclear localization, DNA binding and
FT repressor activity on E-cadherin/CDH1 promoter; when
FT associated with E-191. Abolishes binding to KPNB1, KPNA2,
FT IPO7 and TNPO1 and nuclear localization; when associated
FT with E-161 and/or E-220."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 191
FT /note="R->E: Mildly reduces binding to KPNB1 and nuclear
FT import. Strongly reduces binding to KPNB1 and nuclear
FT import; when associated with A-193. Loss of binding to
FT KPNB1 and nuclear import; when associated with A-193 and A-
FT 196."
FT /evidence="ECO:0000269|PubMed:24699649"
FT MUTAGEN 191
FT /note="R->E: Mildly reduces binding to KPNB1. Does not
FT affect binding to KPNA2, IPO7 or TNPO1."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 193
FT /note="W->A: Mildly reduces binding to KPNB1 and nuclear
FT import. Strongly reduces binding to KPNB1 and nuclear
FT import; when associated with E-191. Loss of binding to
FT KPNB1 and nuclear import; when associated with E-191 and A-
FT 196."
FT /evidence="ECO:0000269|PubMed:24699649"
FT MUTAGEN 196
FT /note="Q->A: Loss of binding to KPNB1 and nuclear import;
FT when associated with E-191 and A-193."
FT /evidence="ECO:0000269|PubMed:24699649"
FT MUTAGEN 203
FT /note="T->A: Abolishes LATS2 phosphorylation. Does not
FT affect binding to LATS2. Reduces protein stability. Equally
FT distributed between nucleus and cytoplasm. Increases
FT capacity to associate with nuclear pore importins. Unable
FT to accumulate in the nucleus. Does not abrogate function."
FT /evidence="ECO:0000269|PubMed:21952048"
FT MUTAGEN 203
FT /note="T->E: Exclusively localizes to the cytoplasm.
FT Reduces capacity to associate with nuclear pore importins.
FT Unable to enter the nucleus. Does not abrogate function."
FT /evidence="ECO:0000269|PubMed:21952048"
FT MUTAGEN 210
FT /note="C->A: Impairs binding to KPNB1, IPO7 and TNPO1 and
FT abolishes binding to KPNA2. Localizes to cytoplasm and
FT nucleus."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 215
FT /note="R->E: Impairs binding to KPNB1, KPNA2, IPO7 and
FT TNPO1. No change in subcellular localization."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 220
FT /note="R->E: Does not affect binding to KPNB1, KPNA2, IPO7
FT or TNPO1. No change in subcellular localization. Impairs
FT binding to KPNB1, KPNA2, IPO7 and TNPO1; when associated
FT with E-222 and E-224. Impairs binding to KPNB1, KPNA2, IPO7
FT and TNPO1 and abolishes nuclear localization, DNA binding
FT and repressor activity on E-cadherin/CDH1 promoter; when
FT associated with E-224. Abolishes binding to KPNB1, KPNA2,
FT IPO7 and TNPO1 and nuclear localization; when associated
FT with E-161 and/or E-187."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 222
FT /note="N->E: Does not affect binding to KPNB1, KPNA2, IPO7
FT or TNPO1. No change in subcellular localization. Impairs
FT binding to KPNB1, KPNA2, IPO7 and TNPO1; when associated
FT with E-220 and E-224."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 224
FT /note="R->E: Does not affect binding to KPNB1, KPNA2, IPO7
FT or TNPO1. No change in subcellular localization. Impairs
FT binding to KPNB1, KPNA2, IPO7 and TNPO1; when associated
FT with E-220 and E-222. Impairs binding to KPNB1, KPNA2, IPO7
FT and TNPO1 and abolishes nuclear localization, DNA binding
FT and repressor activity on E-cadherin/CDH1 promoter; when
FT associated with E-220."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 224
FT /note="R->E: Mildly reduces binding to KPNB1 and nuclear
FT import. Strongly reduces binding to KPNB1 and nuclear
FT import; when associated with A-228."
FT /evidence="ECO:0000269|PubMed:24699649"
FT MUTAGEN 228
FT /note="Q->A: Very minor effect on binding to KPNB1 and
FT nuclear import. Strongly reduces binding to KPNB1 and
FT nuclear import; when associated with E-224."
FT /evidence="ECO:0000269|PubMed:24699649"
FT MUTAGEN 232..235
FT /note="DVKK->KVEE: Does not affect binding to KPNB1, KPNA2,
FT IPO7 or TNPO1."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 238
FT /note="C->A: Impairs binding to KPNB1 and IPO7 and
FT abolishes binding to KPNA2 and TNPO1 and nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 239
FT /note="Q->E: Does not affect binding to KPNB1, KPNA2, IPO7,
FT TNPO1 or DNA."
FT /evidence="ECO:0000269|PubMed:19386897"
FT MUTAGEN 246
FT /note="S->A: Decreases repression activity on E-
FT cadherin/CDH1, occludin and aromatase promoters.
FT Preferentially localizes to the cytoplasm. Abolishes
FT phosphorylation by PAK1."
FT /evidence="ECO:0000269|PubMed:15833848"
FT MUTAGEN 247
FT /note="R->E: Mildly reduces binding to KPNB1 and nuclear
FT import."
FT /evidence="ECO:0000269|PubMed:24699649"
FT CONFLICT 46
FT /note="P -> L (in Ref. 4; BAG36039)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="F -> S (in Ref. 7; AAF32527)"
FT /evidence="ECO:0000305"
FT HELIX 3..5
FT /evidence="ECO:0007829|PDB:2Y48"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:3W5K"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:3W5K"
FT HELIX 166..173
FT /evidence="ECO:0007829|PDB:3W5K"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:3W5K"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:3W5K"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:3W5K"
FT HELIX 192..200
FT /evidence="ECO:0007829|PDB:3W5K"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:3W5K"
FT STRAND 216..219
FT /evidence="ECO:0007829|PDB:3W5K"
FT HELIX 220..227
FT /evidence="ECO:0007829|PDB:3W5K"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:3W5K"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:3W5K"
FT HELIX 248..256
FT /evidence="ECO:0007829|PDB:3W5K"
SQ SEQUENCE 264 AA; 29083 MW; 70E298C9BB154115 CRC64;
MPRSFLVRKP SDPNRKPNYS ELQDSNPEFT FQQPYDQAHL LAAIPPPEIL NPTASLPMLI
WDSVLAPQAQ PIAWASLRLQ ESPRVAELTS LSDEDSGKGS QPPSPPSPAP SSFSSTSVSS
LEAEAYAAFP GLGQVPKQLA QLSEAKDLQA RKAFNCKYCN KEYLSLGALK MHIRSHTLPC
VCGTCGKAFS RPWLLQGHVR THTGEKPFSC PHCSRAFADR SNLRAHLQTH SDVKKYQCQA
CARTFSRMSL LHKHQESGCS GCPR
