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TM9SF2
Identifikatori
Aliasi	TM9SF2
Vanjski ID-jevi	OMIM: 604678 MGI: 1915309 HomoloGene: 21004 GeneCards: TM9SF2
Lokacija gena (čovjek)
Hrom.	Hromosom 13 (čovjek)
Kraj	99,564,048 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	122,397,016 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ortolozi
	9375
	68059
	ENSG00000125304
	ENSMUSG00000025544
	Q99805
	P58021
	NM_004800
	NM_080556
	NP_004791
	NP_542123
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein 1 porodice TSC22 domena je protein koji je kod ljudi kodiran genom TSC22D1.^[5]^[6]

TSC22 kodira transkripcijski faktor i pripada velikoj porodici geni ranog odgovora.^[7] TSC22D1 kodira transkripcijski faktor i pripada velikoj porodici gena za rani odgovor. Putem fluorescentne ibridizacije in situ, Jay et al. (1996) locirali su gen TSC22D1 na hromosomu 13, sekvenca 13q14.^[8]

TSC22D1 tvori homodimere, preko konzerviranog domena leucinskog zatvarača i heterodimerizuje s TSC22D4. TSC22D1 ima transkripcijsku represorsku aktivnost.^[9]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.073 aminokiseline, a molekulska težina 109.677 Da.^[10].

10	20	30	40	50
MHQPPESTAA	AAAAADISAR	KMAHPAMFPR	RGSGSGSASA	LNAAGTGVGS
NATSSEDFPP	PSLLQPPPPA	ASSTSGPQPP	PPQSLNLLSQ	AQLQAQPLAP
GGTQMKKKSG	FQITSVTPAQ	ISASISSNNS	IAEDTESYDD	LDESHTEDLS
SSEILDVSLS	RATDLGEPER	SSSEETLNNF	QEAETPGAVS	PNQPHLPQPH
LPHLPQQNVV	INGNAHPHHL	HHHHQIHHGH	HLQHGHHHPS	HVAVASASIT
GGPPSSPVSR	KLSTTGSSDS	ITPVAPTSAV	SSSGSPASVM	TNMRAPSTTG
GIGINSVTGT	STVNNVNITA	VGSFNPNVTS	SMLGNVNIST	SNIPSAAGVS
VGPGVTSGVN	VNILSGMGNG	TISSSAAVSS	VPNAAAGMTG	GSVSSQQQQP
TVNTSRFRVV	KLDSSSEPFK	KGRWTCTEFY	EKENAVPATE	GVLINKVVET
VKQNPIEVTS	ERESTSGSSV	SSSVSTLSHY	TESVGSGEMG	APTVVVQQQQ
QQQQQQQQQP	ALQGVTLQQM	DFGSTGPQSI	PAVSIPQSIS	QSQISQVQLQ
SQELSYQQKQ	GLQPVPLQAT	MSAATGIQPS	PVNVVGVTSA	LGQQPSISSL
AQPQLPYSQA	APPVQTPLPG	APPPQQLQYG	QQQPMVSTQM	APGHVKSVTQ
NPASEYVQQQ	PILQTAMSSG	QPSSAGVGAG	TTVIPVAQPQ	GIQLPVQPTA
VPAQPAGASV	QPVGQAPAAV	SAVPTGSQIA	NIGQQANIPT	AVQQPSTQVP
PSVIQQGAPP	SSQVVPPAQT	GIIHQGVQTS	APSLPQQLVI	ASQSSLLTVP
PQPQGVEPVA	QGIVSQQLPA	VSSLPSASSI	SVTSQVSSTG	PSGMPSAPTN
LVPPQNIAQT	PATQNGNLVQ	SVSQPPLIAT	NTNLPLAQQI	PLSSTQFSAQ
SLAQAIGSQI	EDARRAAEPS	LVGLPQTISG	DSGGMSAVSD	GSSSSLAASA
SLFPLKVLPL	TTPLVDGEDE	SSSGASVVAI	DNKIEQAMDL	VKSHLMYAVR
EEVEVLKEQI	KELIEKNSQL	EQENNLLKTL	ASPEQLAQFQ	AQLQTGSPPA
TTQPQGTTQP	PAQPASQGSG	PTA

Simboli

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

Kloniranje i ekspresija

Skriningom male količine klonova u biblioteci cDNK, od 6-sedmičnih mišjih embriona, Jay et al. (1996) klonirali su TSC22D1, koji su nazvali TSC22. Izvedeni protein sa 144 aminokiseline imao je izračunatu molekulsku masu od oko 16,7 kD i leucinski zatvarač, C-kraj bogat glutaminom i prolinom i dva potencijalna mjesta fosforilacije. TSC22 dijeli značajnu homolog[iju sa Tsc22 kod miševa, pacova i kokoši, a 69% identiteta sa svinjskim Dsipom i 52% identiteta sa proteinom za kratkovidnost kod Drosophila. Zoo blot analiza otkrila je srodne sekvence kod svih zastupljenih kičmenjaka i voćnih mušica. Signal nije otkriven u dagnjama, nematodama, kvascima i bakterijama.

Prema Southwestern scriningu, Ohta et al. (1996) identificirali su pacovaa Tsc22 vezanjem za G–C-bogati element promotora CNP. Koristili su ovu sekvencu za oblikovanje prajmera i kloniranja ljudskog TSC22, pomoću PCR-a i 3' i 5' RACE biblioteke cDNK fetusnog bubrega. Ljudski TSC22 razlikuje se od proteina pacova po inserciji jednog ostatka i jednoj zamjeni. Proteini pacova i miša su identični.

Prema Northern blot analizi, Jay et al (1996) i Ohta et al. (1996) utvrdili su da je TSC22 eksprimiran kao 1,8 kb transkript u različitim količinama u svim tkivima fetusa i odraslih, osim leukocita periferne krvi. Transkript od oko pet kb također je otkriven u skeletnim mišićima.^[11]

Funkcija gena

Analizom pomaka mobilnosti i kotransfekcijom s reporter-plazmidom, Ohta et al. (1996) potvrdili su da se pacovski Tsc22 veže i može podstaknuti ekspresiju iz sekvence CNP promotora, bogate GC-om. U endotelnim ćelijama ljudske aorte ekspresiju TSC22 stimulirali su citokini, uključujući TGFB, i brzo se izgubila. Ekspresija TSC22 iRNK korelira sa povećanim nivoom CNP iRNK.

Analizom 2-hibrida kvasca, ispitivanjem pomaka gela i eksperimentima povlačenja GST-a, Kester et al. (1999) potvrdili su da TSC22D1 formira homodimere, preko konzerviranog domena leucinskog zatvarača i da stupa u interakciju s TSC22D4, formiranjem heterodimera. Pokazali su da TSC22D1 ima transkripcijsku represorsku aktivnost.^[12]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000125304 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000025544 - 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.
^ Jay P, Ji JW, Marsollier C, Taviaux S, Berge-Lefranc JL, Berta P (Jul 1996). "Cloning of the human homologue of the TGF beta-stimulated clone 22 gene". Biochem Biophys Res Commun. 222 (3): 821–6. doi:10.1006/bbrc.1996.0825. PMID 8651929.
^ Ohta S, Shimekake Y, Nagata K (Mar 1997). "Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter". Eur J Biochem. 242 (3): 460–6. doi:10.1111/j.1432-1033.1996.460rr.x. PMID 9022669.
^ "Entrez Gene: TSC22D1 TSC22 domain family, member 1".
^ Jay, P., Ji, J. W., Marsollier, C., Taviaux, S., Berge-Lefranc, J.-L., Berta, P. Cloning of the human homologue of the TGF-beta-stimulated clone 22 gene. Biochem. Biophys. Res. Commun. 222: 821-826, 1996. PubMed: 8651929
^ Kester HA, Blanchetot C, den Hertog J, van der Saag PT, van der Burg B (septembar 1999). "Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity". J. Biol. Chem. 274 (39): 27439–47. doi:10.1074/jbc.274.39.27439. PMID 10488076.
^ "UniProt, Q15714". Pristupljeno 6. 8. 2021.
^ Ohta, S., Shimekake, Y., Nagata, K. Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter. Europ. J. Biochem. 242: 460-466, 1996. PubMed: 9022669
^ Kester, H. A., Blanchetot, C., den Hertog, J., van der Saag, P. T., van der Burg, B. Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity. J. Biol. Chem. 274: 27439-27447, 1999. PubMed: 10488076

Dopunska literatura

Shibanuma M, Kuroki T, Nose K (1992). "Isolation of a gene encoding a putative leucine zipper structure that is induced by transforming growth factor beta 1 and other growth factors". J. Biol. Chem. 267 (15): 10219–24. doi:10.1016/S0021-9258(19)50006-0. PMID 1587811.
Dmitrenko VV, Garifulin OM, Shostak EA, et al. (1997). "[The characteristics of different types of mRNA expressed in the human brain]". Tsitol. Genet. 30 (5): 41–7. PMID 9026990.
Kester HA, Blanchetot C, den Hertog J, et al. (1999). "Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity". J. Biol. Chem. 274 (39): 27439–47. doi:10.1074/jbc.274.39.27439. PMID 10488076.
Hino S, Kawamata H, Uchida D, et al. (2001). "Nuclear translocation of TSC-22 (TGF-beta-stimulated clone-22) concomitant with apoptosis: TSC-22 as a putative transcriptional regulator". Biochem. Biophys. Res. Commun. 278 (3): 659–64. doi:10.1006/bbrc.2000.3840. PMID 11095965.
Hino S, Kawamata H, Omotehara F, et al. (2002). "Leucine zipper structure of TSC-22 (TGF-beta stimulated clone-22) markedly inhibits the anchorage-independent growth of salivary gland cancer cells". Oncol. Rep. 9 (2): 371–4. doi:10.3892/or.9.2.371. PMID 11836610.
Hino S, Kawamata H, Omotehara F, et al. (2002). "Cytoplasmic TSC-22 (transforming growth factor-beta-stimulated clone-22) markedly enhances the radiation sensitivity of salivary gland cancer cells". Biochem. Biophys. Res. Commun. 292 (4): 957–63. doi:10.1006/bbrc.2002.6776. PMID 11944908.
Ohara O, Nagase T, Mitsui G, et al. (2003). "Characterization of size-fractionated cDNA libraries generated by the in vitro recombination-assisted method". DNA Res. 9 (2): 47–57. doi:10.1093/dnares/9.2.47. PMID 12056414.
Gupta RA, Sarraf P, Brockman JA, et al. (2003). "Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22". J. Biol. Chem. 278 (9): 7431–8. doi:10.1074/jbc.M208076200. PMID 12468551.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Sugawara F, Yamada Y, Watanabe R, et al. (2004). "The role of the TSC-22 (-396) A/G variant in the development of diabetic nephropathy". Diabetes Res. Clin. Pract. 60 (3): 191–7. doi:10.1016/S0168-8227(03)00038-X. PMID 12757981.
Uchida D, Omotehara F, Nakashiro K, et al. (2003). "Posttranscriptional regulation of TSC-22 (TGF-beta-stimulated clone-22) gene by TGF-beta 1". Biochem. Biophys. Res. Commun. 305 (4): 846–54. doi:10.1016/S0006-291X(03)00854-4. PMID 12767908.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Choi SJ, Moon JH, Ahn YW, et al. (2005). "Tsc-22 enhances TGF-beta signaling by associating with Smad4 and induces erythroid cell differentiation". Mol. Cell. Biochem. 271 (1–2): 23–8. doi:10.1007/s11010-005-3456-7. PMID 15881652. S2CID 23414101.
Rentsch CA, Cecchini MG, Schwaninger R, et al. (2006). "Differential expression of TGFbeta-stimulated clone 22 in normal prostate and prostate cancer". Int. J. Cancer. 118 (4): 899–906. doi:10.1002/ijc.21449. PMID 16106424.
Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
Lu Y, Kitaura J, Oki T, et al. (2007). "Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD". Leukemia. 21 (11): 2246–57. doi:10.1038/sj.leu.2404883. PMID 17690703.

Vanjski linkovi

TSC22D1 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000125304 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000025544 - 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.

[pmid8651929-5] Jay P, Ji JW, Marsollier C, Taviaux S, Berge-Lefranc JL, Berta P (Jul 1996). "Cloning of the human homologue of the TGF beta-stimulated clone 22 gene". Biochem Biophys Res Commun. 222 (3): 821–6. doi:10.1006/bbrc.1996.0825. PMID 8651929.

[pmid9022669-6] Ohta S, Shimekake Y, Nagata K (Mar 1997). "Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter". Eur J Biochem. 242 (3): 460–6. doi:10.1111/j.1432-1033.1996.460rr.x. PMID 9022669.

[entrez-7] "Entrez Gene: TSC22D1 TSC22 domain family, member 1".

[8] Jay, P., Ji, J. W., Marsollier, C., Taviaux, S., Berge-Lefranc, J.-L., Berta, P. Cloning of the human homologue of the TGF-beta-stimulated clone 22 gene. Biochem. Biophys. Res. Commun. 222: 821-826, 1996. PubMed: 8651929

[pmid10488076-9] Kester HA, Blanchetot C, den Hertog J, van der Saag PT, van der Burg B (septembar 1999). "Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity". J. Biol. Chem. 274 (39): 27439–47. doi:10.1074/jbc.274.39.27439. PMID 10488076.

[UniProt-10] "UniProt, Q15714". Pristupljeno 6. 8. 2021.

[11] Ohta, S., Shimekake, Y., Nagata, K. Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter. Europ. J. Biochem. 242: 460-466, 1996. PubMed: 9022669

[12] Kester, H. A., Blanchetot, C., den Hertog, J., van der Saag, P. T., van der Burg, B. Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity. J. Biol. Chem. 274: 27439-27447, 1999. PubMed: 10488076

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