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SNAI2

October 21, 2023

Zinc finger protein SNAI2 is a transcription factor that in humans is encoded by the SNAI2 gene. It promotes the differentiation and migration of certain cells and has roles in initiating gastrulation.[5][6][7]

SNAI2
Identifiers
AliasesSNAI2, SLUG, SLUGH1, SNAIL2, WS2D, snail family transcriptional repressor 2, SLUGH
External IDsOMIM: 602150 MGI: 1096393 HomoloGene: 31127 GeneCards: SNAI2
Orthologs
SpeciesHumanMouse
Entrez

6591

20583

Ensembl

ENSG00000019549

ENSMUSG00000022676

UniProt

O43623

P97469

RefSeq (mRNA)

NM_003068

NM_011415

RefSeq (protein)

NP_003059

NP_035545

Location (UCSC)Chr 8: 48.92 – 48.92 MbChr 16: 14.52 – 14.53 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function Edit

This gene encodes a member of the Snail superfamily of C2H2-type zinc finger transcription factors. The encoded protein acts as a transcriptional repressor that binds to E-box motifs and is also likely to repress E-cadherin transcription in breast carcinoma. This protein is involved in epithelial-mesenchymal transitions and has antiapoptotic activity. It regulates differentiation and migration of neural crest cells along with other genes (e.g. FOXD3, SOX9 and SOX10, BMPs) in embryonic life. Mutations in this gene may be associated with sporadic cases of neural tube defects.[7][8]

SNAI2 downregulates expression of E-cadherin in premigratory neural crest cells; thus, SNAI2 induces tightly bound epithelial cells to break into a loose mesenchymal phenotype, allowing gastrulation of mesoderm in the developing embryo.[9][10] Structurally similar to anti-apoptotic Ces-1 in C. elegans, SLUG is a negative regulator of productive cell death in the developing embryo and adults.[9][11]

Clinical significance Edit

Widely expressed in human tissues, SLUG is most notably absent in peripheral blood leukocytes, adult liver, and both fetal and adult brain tissues.[11] SLUG plays a role in breast carcinoma as well as leukemia by downregulation of E-cadherin, which supports mesenchymal phenotype by shifting expression from a Type I to Type II cadherin profile.[11][12] Maintenance of mesenchymal phenotype enables metastasis of tumor cells, though SLUG is expressed in carcinomas regardless to invasiveness.[9][10][11] A knockout model using chick embryos has also showed inhibition of mesodermal and neural crest delamination; chick embryo Slug gain of function appears to increase neural crest production.[9] Mutations in Slug are associated with loss of pregnancy during gastrulation in some animals.[9]

Interactions Edit

BMPs precede expression of SLUG, and are suspected as the immediate upstream inducers of gene expression.[10][13]

References Edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000019549 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022676 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Rhim H, Savagner P, Thibaudeau G, Thiery JP, Pavan WJ (Jan 1998). "Localization of a neural crest transcription factor, Slug, to mouse chromosome 16 and human chromosome 8". Mammalian Genome. 8 (11): 872–3. doi:10.1007/s003359900601. PMID 9337409. S2CID 2177885.
  6. ^ Cohen ME, Yin M, Paznekas WA, Schertzer M, Wood S, Jabs EW (August 1998). "Human SLUG gene organization, expression, and chromosome map location on 8q". Genomics. 51 (3): 468–71. doi:10.1006/geno.1998.5367. PMID 9721220.
  7. ^ a b "Entrez Gene: SNAI2 snail homolog 2 (Drosophila)".
  8. ^ Stegmann, K.; Boecker, J.; Kosan, C.; Ermert, A.; Kunz, J.; Koch, M. C. (August 1999). "Human transcription factor SLUG: mutation analysis in patients with neural tube defects and identification of a missense mutation (D119E) in the Slug subfamily-defining region". Mutation Research. 406 (2–4): 63–69. doi:10.1016/s1383-5726(99)00002-3. ISSN 0027-5107. PMID 10479723.
  9. ^ a b c d e Nieto MA (March 2002). "The snail superfamily of zinc-finger transcription factors". Nature Reviews Molecular Cell Biology. 3 (3): 155–66. doi:10.1038/nrm757. PMID 11994736. S2CID 8330951.
  10. ^ a b c Carlson BM (2013). Human Embryology and Developmental Biology (5th ed.). Philadelphia, PA: Elsevier Health Sciences. pp. 101–102, 106, 313, 362, 382. ISBN 978-1-4557-2794-0.
  11. ^ a b c d Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T, Look AT (September 1999). "SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein". Molecular Cell. 4 (3): 343–52. doi:10.1016/S1097-2765(00)80336-6. PMID 10518215.
  12. ^ Kalluri R, Weinberg RA (June 2009). "The basics of epithelial-mesenchymal transition". The Journal of Clinical Investigation. 119 (6): 1420–8. doi:10.1172/jci39104. PMC 2689101. PMID 19487818.
  13. ^ Sakai D, Wakamatsu Y (2005). "Regulatory mechanisms for neural crest formation". Cells Tissues Organs. 179 (1–2): 24–35. doi:10.1159/000084506. PMID 15942190. S2CID 1886380.

Further reading Edit

  • Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Savagner P, Yamada KM, Thiery JP (June 1997). "The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition". The Journal of Cell Biology. 137 (6): 1403–19. doi:10.1083/jcb.137.6.1403. PMC 2132541. PMID 9182671.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Stegmann K, Boecker J, Kosan C, Ermert A, Kunz J, Koch MC (August 1999). "Human transcription factor SLUG: mutation analysis in patients with neural tube defects and identification of a missense mutation (D119E) in the Slug subfamily-defining region". Mutation Research. 406 (2–4): 63–9. doi:10.1016/S1383-5726(99)00002-3. PMID 10479723.
  • Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T, Look AT (September 1999). "SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein". Molecular Cell. 4 (3): 343–52. doi:10.1016/S1097-2765(00)80336-6. PMID 10518215.
  • Hemavathy K, Guru SC, Harris J, Chen JD, Ip YT (July 2000). "Human Slug is a repressor that localizes to sites of active transcription". Molecular and Cellular Biology. 20 (14): 5087–95. doi:10.1128/MCB.20.14.5087-5095.2000. PMC 85958. PMID 10866665.
  • Hajra KM, Chen DY, Fearon ER (March 2002). "The SLUG zinc-finger protein represses E-cadherin in breast cancer". Cancer Research. 62 (6): 1613–8. PMID 11912130.
  • Sánchez-Martín M, Rodríguez-García A, Pérez-Losada J, Sagrera A, Read AP, Sánchez-García I (December 2002). "SLUG (SNAI2) deletions in patients with Waardenburg disease". Human Molecular Genetics. 11 (25): 3231–6. doi:10.1093/hmg/11.25.3231. PMID 12444107.
  • Kajita M, McClinic KN, Wade PA (September 2004). "Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress". Molecular and Cellular Biology. 24 (17): 7559–66. doi:10.1128/MCB.24.17.7559-7566.2004. PMC 506998. PMID 15314165.
  • Catalano A, Rodilossi S, Rippo MR, Caprari P, Procopio A (November 2004). "Induction of stem cell factor/c-Kit/slug signal transduction in multidrug-resistant malignant mesothelioma cells". The Journal of Biological Chemistry. 279 (45): 46706–14. doi:10.1074/jbc.M406696200. PMID 15337769.
  • Uchikado Y, Natsugoe S, Okumura H, Setoyama T, Matsumoto M, Ishigami S, Aikou T (February 2005). "Slug Expression in the E-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma". Clinical Cancer Research. 11 (3): 1174–80. doi:10.1158/1078-0432.1174.11.3. PMID 15709186.
  • Tripathi MK, Misra S, Khedkar SV, Hamilton N, Irvin-Wilson C, Sharan C, Sealy L, Chaudhuri G (April 2005). "Regulation of BRCA2 gene expression by the SLUG repressor protein in human breast cells". The Journal of Biological Chemistry. 280 (17): 17163–71. doi:10.1074/jbc.M501375200. PMC 3092429. PMID 15734731.
  • Tripathi MK, Misra S, Chaudhuri G (April 2005). "Negative regulation of the expressions of cytokeratins 8 and 19 by SLUG repressor protein in human breast cells". Biochemical and Biophysical Research Communications. 329 (2): 508–15. doi:10.1016/j.bbrc.2005.02.006. PMC 3086003. PMID 15737616.
  • Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, Notorfrancesco KL, Cardiff RD, Chodosh LA (September 2005). "The transcriptional repressor Snail promotes mammary tumor recurrence". Cancer Cell. 8 (3): 197–209. doi:10.1016/j.ccr.2005.07.009. PMID 16169465.
  • Chen M, Chen LM, Chai KX (June 2006). "Androgen regulation of prostasin gene expression is mediated by sterol-regulatory element-binding proteins and SLUG". The Prostate. 66 (9): 911–20. doi:10.1002/pros.20325. PMID 16541421. S2CID 23036264.
  • Turner FE, Broad S, Khanim FL, Jeanes A, Talma S, Hughes S, Tselepis C, Hotchin NA (July 2006). "Slug regulates integrin expression and cell proliferation in human epidermal keratinocytes". The Journal of Biological Chemistry. 281 (30): 21321–31. doi:10.1074/jbc.M509731200. PMID 16707493.

October 21, 2023
snai2, zinc, finger, protein, transcription, factor, that, humans, encoded, gene, promotes, differentiation, migration, certain, cells, roles, initiating, gastrulation, identifiersaliases, slug, slugh1, snail2, ws2d, snail, family, transcriptional, repressor, . Zinc finger protein SNAI2 is a transcription factor that in humans is encoded by the SNAI2 gene It promotes the differentiation and migration of certain cells and has roles in initiating gastrulation 5 6 7 SNAI2IdentifiersAliasesSNAI2 SLUG SLUGH1 SNAIL2 WS2D snail family transcriptional repressor 2 SLUGHExternal IDsOMIM 602150 MGI 1096393 HomoloGene 31127 GeneCards SNAI2Gene location Human Chr Chromosome 8 human 1 Band8q11 21Start48 917 598 bp 1 End48 921 740 bp 1 Gene location Mouse Chr Chromosome 16 mouse 2 Band16 A1 16 10 07 cMStart14 523 716 bp 2 End14 527 249 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed intibiastromal cell of endometriumperiodontal fiberseminal vesiculaAchilles tendonhair folliclehuman penisleft uterine tubegumsparietal pleuraTop expressed incondylefossaconjunctival fornixhair folliclevas deferenscalvariamaxillary prominencebody of femurleft lung lobemolarMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionsequence specific DNA binding DNA binding metal ion binding protein binding nucleic acid binding DNA binding transcription factor activity RNA polymerase II specific DNA binding transcription repressor activity RNA polymerase II specific RNA polymerase II transcription regulatory region sequence specific DNA binding chromatin binding DNA binding transcription factor activity transcription factor activity RNA polymerase II distal enhancer sequence specific binding E box bindingCellular componentcytoplasm nucleus nucleoplasmBiological processNotch signaling pathway negative regulation of vitamin D receptor signaling pathway regulation of transcription DNA templated neural crest cell development negative regulation of keratinocyte proliferation regulation of bicellular tight junction assembly positive regulation of cell migration negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage transcription DNA templated cellular response to epidermal growth factor stimulus negative regulation of vitamin D biosynthetic process regulation of chemokine production multicellular organism development negative regulation of chondrocyte differentiation negative regulation of DNA damage response signal transduction by p53 class mediator regulation of osteoblast differentiation osteoblast differentiation canonical Wnt signaling pathway negative regulation of canonical Wnt signaling pathway negative regulation of cell adhesion mediated by integrin negative regulation of anoikis negative regulation of transcription by RNA polymerase II epithelial to mesenchymal transition epithelial to mesenchymal transition involved in endocardial cushion formation cell migration involved in endocardial cushion formation sensory perception of sound desmosome disassembly pigmentation epithelium development negative regulation of extrinsic apoptotic signaling pathway in absence of ligand aortic valve morphogenesis negative regulation of cell adhesion involved in substrate bound cell migration response to radiation cell migration positive regulation of histone acetylation negative regulation of apoptotic process positive regulation of fat cell differentiation white fat cell differentiation roof of mouth development cartilage morphogenesis regulation of branching involved in salivary gland morphogenesis cellular response to ionizing radiation negative regulation of stem cell proliferation Notch signaling involved in heart developmentSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez659120583EnsemblENSG00000019549ENSMUSG00000022676UniProtO43623P97469RefSeq mRNA NM 003068NM 011415RefSeq protein NP 003059NP 035545Location UCSC Chr 8 48 92 48 92 MbChr 16 14 52 14 53 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 Interactions 4 References 5 Further readingFunction EditThis gene encodes a member of the Snail superfamily of C2H2 type zinc finger transcription factors The encoded protein acts as a transcriptional repressor that binds to E box motifs and is also likely to repress E cadherin transcription in breast carcinoma This protein is involved in epithelial mesenchymal transitions and has antiapoptotic activity It regulates differentiation and migration of neural crest cells along with other genes e g FOXD3 SOX9 and SOX10 BMPs in embryonic life Mutations in this gene may be associated with sporadic cases of neural tube defects 7 8 SNAI2 downregulates expression of E cadherin in premigratory neural crest cells thus SNAI2 induces tightly bound epithelial cells to break into a loose mesenchymal phenotype allowing gastrulation of mesoderm in the developing embryo 9 10 Structurally similar to anti apoptotic Ces 1 in C elegans SLUG is a negative regulator of productive cell death in the developing embryo and adults 9 11 Clinical significance EditWidely expressed in human tissues SLUG is most notably absent in peripheral blood leukocytes adult liver and both fetal and adult brain tissues 11 SLUG plays a role in breast carcinoma as well as leukemia by downregulation of E cadherin which supports mesenchymal phenotype by shifting expression from a Type I to Type II cadherin profile 11 12 Maintenance of mesenchymal phenotype enables metastasis of tumor cells though SLUG is expressed in carcinomas regardless to invasiveness 9 10 11 A knockout model using chick embryos has also showed inhibition of mesodermal and neural crest delamination chick embryo Slug gain of function appears to increase neural crest production 9 Mutations in Slug are associated with loss of pregnancy during gastrulation in some animals 9 Interactions EditBMPs precede expression of SLUG and are suspected as the immediate upstream inducers of gene expression 10 13 References Edit a b c GRCh38 Ensembl release 89 ENSG00000019549 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000022676 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Rhim H Savagner P Thibaudeau G Thiery JP Pavan WJ Jan 1998 Localization of a neural crest transcription factor Slug to mouse chromosome 16 and human chromosome 8 Mammalian Genome 8 11 872 3 doi 10 1007 s003359900601 PMID 9337409 S2CID 2177885 Cohen ME Yin M Paznekas WA Schertzer M Wood S Jabs EW August 1998 Human SLUG gene organization expression and chromosome map location on 8q Genomics 51 3 468 71 doi 10 1006 geno 1998 5367 PMID 9721220 a b Entrez Gene SNAI2 snail homolog 2 Drosophila Stegmann K Boecker J Kosan C Ermert A Kunz J Koch M C August 1999 Human transcription factor SLUG mutation analysis in patients with neural tube defects and identification of a missense mutation D119E in the Slug subfamily defining region Mutation Research 406 2 4 63 69 doi 10 1016 s1383 5726 99 00002 3 ISSN 0027 5107 PMID 10479723 a b c d e Nieto MA March 2002 The snail superfamily of zinc finger transcription factors Nature Reviews Molecular Cell Biology 3 3 155 66 doi 10 1038 nrm757 PMID 11994736 S2CID 8330951 a b c Carlson BM 2013 Human Embryology and Developmental Biology 5th ed Philadelphia PA Elsevier Health Sciences pp 101 102 106 313 362 382 ISBN 978 1 4557 2794 0 a b c d Inukai T Inoue A Kurosawa H Goi K Shinjyo T Ozawa K Mao M Inaba T Look AT September 1999 SLUG a ces 1 related zinc finger transcription factor gene with antiapoptotic activity is a downstream target of the E2A HLF oncoprotein Molecular Cell 4 3 343 52 doi 10 1016 S1097 2765 00 80336 6 PMID 10518215 Kalluri R Weinberg RA June 2009 The basics of epithelial mesenchymal transition The Journal of Clinical Investigation 119 6 1420 8 doi 10 1172 jci39104 PMC 2689101 PMID 19487818 Sakai D Wakamatsu Y 2005 Regulatory mechanisms for neural crest formation Cells Tissues Organs 179 1 2 24 35 doi 10 1159 000084506 PMID 15942190 S2CID 1886380 Further reading EditMaruyama K Sugano S January 1994 Oligo capping a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides Gene 138 1 2 171 4 doi 10 1016 0378 1119 94 90802 8 PMID 8125298 Savagner P Yamada KM Thiery JP June 1997 The zinc finger protein slug causes desmosome dissociation an initial and necessary step for growth factor induced epithelial mesenchymal transition The Journal of Cell Biology 137 6 1403 19 doi 10 1083 jcb 137 6 1403 PMC 2132541 PMID 9182671 Suzuki Y Yoshitomo Nakagawa K Maruyama K Suyama A Sugano S October 1997 Construction and characterization of a full length enriched and a 5 end enriched cDNA library Gene 200 1 2 149 56 doi 10 1016 S0378 1119 97 00411 3 PMID 9373149 Stegmann K Boecker J Kosan C Ermert A Kunz J Koch MC August 1999 Human transcription factor SLUG mutation analysis in patients with neural tube defects and identification of a missense mutation D119E in the Slug subfamily defining region Mutation Research 406 2 4 63 9 doi 10 1016 S1383 5726 99 00002 3 PMID 10479723 Inukai T Inoue A Kurosawa H Goi K Shinjyo T Ozawa K Mao M Inaba T Look AT September 1999 SLUG a ces 1 related zinc finger transcription factor gene with antiapoptotic activity is a downstream target of the E2A HLF oncoprotein Molecular Cell 4 3 343 52 doi 10 1016 S1097 2765 00 80336 6 PMID 10518215 Hemavathy K Guru SC Harris J Chen JD Ip YT July 2000 Human Slug is a repressor that localizes to sites of active transcription Molecular and Cellular Biology 20 14 5087 95 doi 10 1128 MCB 20 14 5087 5095 2000 PMC 85958 PMID 10866665 Hajra KM Chen DY Fearon ER March 2002 The SLUG zinc finger protein represses E cadherin in breast cancer Cancer Research 62 6 1613 8 PMID 11912130 Sanchez Martin M Rodriguez Garcia A Perez Losada J Sagrera A Read AP Sanchez Garcia I December 2002 SLUG SNAI2 deletions in patients with Waardenburg disease Human Molecular Genetics 11 25 3231 6 doi 10 1093 hmg 11 25 3231 PMID 12444107 Kajita M McClinic KN Wade PA September 2004 Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress Molecular and Cellular Biology 24 17 7559 66 doi 10 1128 MCB 24 17 7559 7566 2004 PMC 506998 PMID 15314165 Catalano A Rodilossi S Rippo MR Caprari P Procopio A November 2004 Induction of stem cell factor c Kit slug signal transduction in multidrug resistant malignant mesothelioma cells The Journal of Biological Chemistry 279 45 46706 14 doi 10 1074 jbc M406696200 PMID 15337769 Uchikado Y Natsugoe S Okumura H Setoyama T Matsumoto M Ishigami S Aikou T February 2005 Slug Expression in the E cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma Clinical Cancer Research 11 3 1174 80 doi 10 1158 1078 0432 1174 11 3 PMID 15709186 Tripathi MK Misra S Khedkar SV Hamilton N Irvin Wilson C Sharan C Sealy L Chaudhuri G April 2005 Regulation of BRCA2 gene expression by the SLUG repressor protein in human breast cells The Journal of Biological Chemistry 280 17 17163 71 doi 10 1074 jbc M501375200 PMC 3092429 PMID 15734731 Tripathi MK Misra S Chaudhuri G April 2005 Negative regulation of the expressions of cytokeratins 8 and 19 by SLUG repressor protein in human breast cells Biochemical and Biophysical Research Communications 329 2 508 15 doi 10 1016 j bbrc 2005 02 006 PMC 3086003 PMID 15737616 Moody SE Perez D Pan TC Sarkisian CJ Portocarrero CP Sterner CJ Notorfrancesco KL Cardiff RD Chodosh LA September 2005 The transcriptional repressor Snail promotes mammary tumor recurrence Cancer Cell 8 3 197 209 doi 10 1016 j ccr 2005 07 009 PMID 16169465 Chen M Chen LM Chai KX June 2006 Androgen regulation of prostasin gene expression is mediated by sterol regulatory element binding proteins and SLUG The Prostate 66 9 911 20 doi 10 1002 pros 20325 PMID 16541421 S2CID 23036264 Turner FE Broad S Khanim FL Jeanes A Talma S Hughes S Tselepis C Hotchin NA July 2006 Slug regulates integrin expression and cell proliferation in human epidermal keratinocytes The Journal of Biological Chemistry 281 30 21321 31 doi 10 1074 jbc M509731200 PMID 16707493 Retrieved from https en wikipedia org w index php title SNAI2 amp oldid 1171933056, wikipedia, wiki, book, books, library,

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