TM9SF2
| TM9SF2 | |||||||||||||||||||||||||
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| Aliasi | TM9SF2 | ||||||||||||||||||||||||
| Vanjski ID-jevi | OMIM: 604678 MGI: 1915309 HomoloGene: 21004 GeneCards: TM9SF2 | ||||||||||||||||||||||||
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| Ortolozi | |||||||||||||||||||||||||
| Vrste | Čovjek | Miš | |||||||||||||||||||||||
| Entrez | |||||||||||||||||||||||||
| Ensembl | |||||||||||||||||||||||||
| UniProt | |||||||||||||||||||||||||
| RefSeq (mRNK) | |||||||||||||||||||||||||
| RefSeq (bjelančevina) | |||||||||||||||||||||||||
| Lokacija (UCSC) | Chr 13: 99.45 – 99.56 Mb | Chr 14: 122.34 – 122.4 Mb | |||||||||||||||||||||||
| PubMed pretraga | [3] | [4] | |||||||||||||||||||||||
| Wikipodaci | |||||||||||||||||||||||||
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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
[uredi | uredi izvor]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
[uredi | uredi izvor]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
[uredi | uredi izvor]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
[uredi | uredi izvor]- ^ 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
[uredi | uredi izvor]- 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
[uredi | uredi izvor]- TSC22D1 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)