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 27-MAR-2024, entry version 220. 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, UBIQUITINATION BY FBXL5, AND PHOSPHORYLATION BY RP LATS2. RX PubMed=24157836; DOI=10.1093/nar/gkt935; RA Vinas-Castells R., Frias A., Robles-Lanuza E., Zhang K., Longmore G.D., RA Garcia de Herreros A., Diaz V.M.; RT "Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and RT stability."; RL Nucleic Acids Res. 42:1079-1094(2014). RN [29] 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 [30] RP DEUBIQUITINATION BY USP37. RX PubMed=31911859; RA Xiao Z., Chang L., Kim J., Zhang P., Hang Q., Yap S., Guo Y., Zhou Z., RA Zeng L., Hu X., Siverly A., Sun Y., Ma L.; RT "USP37 is a SNAI1 deubiquitinase."; RL Am. J. Cancer Res. 9:2749-2759(2019). RN [31] {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 [32] 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 [33] 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:24157836, ECO:0000269|PubMed:24699649, CC ECO:0000269|PubMed:25893292}. Cytoplasm {ECO:0000269|PubMed:15448698, CC ECO:0000269|PubMed:15833848}. Note=Once phosphorylated (probably on CC Ser-107, Ser-111, Ser-115 and Ser-119) it is exported from the nucleus CC to the cytoplasm where subsequent phosphorylation of the destruction CC motif and ubiquitination involving BTRC occurs. CC {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 (PubMed:24157836). {ECO:0000269|PubMed:15647282, CC ECO:0000269|PubMed:19923321, ECO:0000269|PubMed:20305697, CC ECO:0000269|PubMed:24157836, ECO:0000305|PubMed:15448698}. CC -!- PTM: Ubiquitinated on Lys-98, Lys-137 and Lys-146 by FBXL14 and BTRC CC leading to degradation (PubMed:19955572). BTRC-triggered ubiquitination CC requires previous GSK3B-mediated SNAI1 phosphorylation. Ubiquitination CC induced upon interaction with NOTCH1 or TP53/p53 is mediated by MDM2 CC (PubMed:20385133). Ubiquitinated in a FBXL5-dependent manner; CC preventing interaction with DNA and promoting its degradation CC (PubMed:24157836). Deubiquitinated by USP37; leading to stabilization CC (PubMed:31911859). {ECO:0000269|PubMed:19955572, CC ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:24157836, CC ECO:0000269|PubMed:31911859}. 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="https://atlasgeneticsoncology.org/gene/452/SNAI1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 526. DR CORUM; O95863; -. DR DIP; DIP-50870N; -. DR IntAct; O95863; 71. DR MINT; O95863; -. DR STRING; 9606.ENSP00000244050; -. DR GlyCosmos; O95863; 1 site, 1 glycan. 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; 9606-ENSP00000244050; -. DR PeptideAtlas; O95863; -. DR ProteomicsDB; 51096; -. DR Antibodypedia; 3135; 1062 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 AGR; HGNC:11128; -. DR CTD; 6615; -. DR DisGeNET; 6615; -. DR GeneCards; SNAI1; -. DR HGNC; HGNC:11128; SNAI1. DR HPA; ENSG00000124216; Tissue enhanced (adipose). 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; TRKAFNC; -. DR OrthoDB; 658032at2759; -. DR PhylomeDB; O95863; -. DR TreeFam; TF315515; -. DR PathwayCommons; O95863; -. DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription. DR Reactome; R-HSA-9758919; Epithelial-Mesenchymal Transition (EMT) during gastrulation. DR Reactome; R-HSA-9762293; Regulation of CDH11 gene transcription. DR SignaLink; O95863; -. DR SIGNOR; O95863; -. DR BioGRID-ORCS; 6615; 23 hits in 1186 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 101 other cell types or tissues. 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: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:0060070; P:canonical Wnt signaling pathway; IMP: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:0007219; P:Notch signaling pathway; 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:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:UniProtKB. DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; IMP:BHF-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; 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 Gene3D; 3.30.160.60; Classic Zinc Finger; 4. DR IDEAL; IID00363; -. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR23235:SF138; FINGER PROTEIN, PUTATIVE-RELATED; 1. DR PANTHER; PTHR23235; KRUEPPEL-LIKE TRANSCRIPTION FACTOR; 1. DR Pfam; PF00096; zf-C2H2; 2. DR Pfam; PF13912; zf-C2H2_6; 1. DR SMART; SM00355; ZnF_C2H2; 4. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4. DR Genevisible; O95863; HS. 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 FT E-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 FT E-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; FT A-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; FT A-115 and A-119. Increases protein stability, does not FT affect repressor activity on E-cadherin 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-104. Impairs FT phosphorylation in the serine-rich region; when associated FT with A-92 and A-104. Abolishes 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; FT A-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; FT A-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; FT A-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 FT E-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 FT A-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 FT A-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 FT E-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 //