SNAI2

SNAI2
Identifikatori
Aliasi	SNAI2
Vanjski ID-jevi	OMIM: 602150 MGI: 1096393 HomoloGene: 31127 GeneCards: SNAI2
Lokacija gena (čovjek)
Hrom.	Hromosom 8 (čovjek)
Kraj	48,921,740 bp
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	14,527,249 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• sequence-specific DNA binding; • vezivanje sa DNK; • vezivanje iona metala; • GO:0001948, GO:0016582 vezivanje za proteine; • nucleic acid binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • chromatin binding; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; • E-box binding;
Ćelijska komponenta	• citoplazma; • jedro; • nukleoplazma;
Biološki proces	• Notch signaling pathway; • negative regulation of vitamin D receptor signaling pathway; • GO:0009373 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; • GO:1901227 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; • sluh; • 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; • Ćelijska migracija; • 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 development;
	Izvori:Amigo / QuickGO
Ortolozi
	6591
	20583
	ENSG00000019549
	ENSMUSG00000022676
	O43623
	P97469
	NM_003068
	NM_011415
	NP_003059
	NP_035545
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein SNAI2 cinkovog prsta je transkripcijski faktor koji je kod ljudi kodiran genom SNAI2. Podstiče diferencijaciju i migraciju određenih ćelija i ima ulogu u pokretanju gastrulacije.^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 268 aminokiselina, а molekulska težina 29.986 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MPRSFLVKKH	FNASKKPNYS	ELDTHTVIIS	PYLYESYSMP	VIPQPEILSS
GAYSPITVWT	TAAPFHAQLP	NGLSPLSGYS	SSLGRVSPPP	PSDTSSKDHS
GSESPISDEE	ERLQSKLSDP	HAIEAEKFQC	NLCNKTYSTF	SGLAKHKQLH
CDAQSRKSFS	CKYCDKEYVS	LGALKMHIRT	HTLPCVCKIC	GKAFSRPWLL
QGHIRTHTGE	KPFSCPHCNR	AFADRSNLRA	HLQTHSDVKK	YQCKNCSKTF
SRMSLLHKHE	ESGCCVAH

Funkcija

Ovaj gen kodira člana nadporodice puževa tipa tranckripcijskog faktora cinkovih prstiju. Kodirani protein djeluje kao represortranskripcije koji se veže za motive E-kutija i također vjerojatno potiskuje E-kadherinsku transkripciju u karcinomu dojke. Ovaj protein je uključen u epitelno-mezenhimske tranzicije i ima antiapoptotsku aktivnost. Regulira diferencijaciju i migraciju čelija nervnog grebena, zajedno s produktima drugih gena (npr. FOXD3, SOX9 i SOX10, BMP) u embrionskom stadiju. Mutacije u ovom genu mogu biti povezane sa sporadičnim slučajevima defekata nervne cijevi.^[7]^[9]

SNAI2 snižava ekspresiju E-kadherina u ćelijama prehladanog nervnog grebena; stoga, SNAI2 inducira čvrsto vezane epitelne ćelijee da se razbiju u labavi mezenhimski fenotip, dopuštajući gastrulaciju mezoderma u embriju u razvoju.^[10]^[11] Strukturno je sličan antiapoptotskom Ces-1 u C. elegans. SLUG je negativni regulator produktivne ćelijske smrti embrijona u razvoju i odraslih.^[10]^[12]

Klinički značaj

Široko eksprimiran u ljudskim tkivima, SLUG je najviše prisutan u leukocitima periferne krvi, jetri odraslih i u tkivima mozga fetusa i odraslih.^[12] 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.^[12]^[13] Održavanje mezenhimskog fenotipa omogućava metastaziranje tumorskih ćelija, iako se SLUG eksprimira u karcinomima bez obzira na invazivnost.^[10]^[11]^[12] Model nokauta koji koristi kokošije embrione također je pokazao inhibiciju dezaminacije mezodermnog i nervnog grebena; izgleda da dobitak funkcije puža povećava proizvodnju nervnog grebena.^[10] Mutacije u pužu, kod nekih životinja povezane su s gubitkom trudnoća tokom gastrulacije.^[10]

Interakcije

BMP prethode ekspresiji SLUG -a i sumnja se da su neposredni uzvodni induktori ekspresije gena.^[11]^[14]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000019549 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022676 - Ensembl, maj 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)".
^ "UniProt, O43623" (jezik: engleski). Pristupljeno 21. 9. 2021.
^ 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 (mart 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 izd.). Philadelphia, PA: Elsevier Health Sciences. str. 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 (septembar 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 (jezik: engleski). 4 (3): 343–52. doi:10.1016/S1097-2765(00)80336-6. PMID 10518215.
^ Kalluri R, Weinberg RA (juni 2009). "The basics of epithelial-mesenchymal transition". The Journal of Clinical Investigation (jezik: engleski). 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.

Dopunska literatura

Maruyama K, Sugano S (januar 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 (juni 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 (oktobar 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 (septembar 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 (juli 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 (mart 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 (decembar 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 (septembar 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 (novembar 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 (februar 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. 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 (septembar 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 (juni 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 (juli 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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000019549 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022676 - Ensembl, maj 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.

[pmid9337409-5] 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.

[pmid9721220-6] 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.

[entrez-7] "Entrez Gene: SNAI2 snail homolog 2 (Drosophila)".

[UniProt-8] "UniProt, O43623" (jezik: engleski). Pristupljeno 21. 9. 2021.

[9] 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.

[Nieto_2002-10] Nieto MA (mart 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.

[Carlson_2013-11] Carlson BM (2013). Human Embryology and Developmental Biology (5th izd.). Philadelphia, PA: Elsevier Health Sciences. str. 101–102, 106, 313, 362, 382. ISBN 978-1-4557-2794-0.

[Inukai_1999-12] Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T, Look AT (septembar 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 (jezik: engleski). 4 (3): 343–52. doi:10.1016/S1097-2765(00)80336-6. PMID 10518215.

[13] Kalluri R, Weinberg RA (juni 2009). "The basics of epithelial-mesenchymal transition". The Journal of Clinical Investigation (jezik: engleski). 119 (6): 1420–8. doi:10.1172/jci39104. PMC 2689101. PMID 19487818.

[14] 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.

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