Timozin α1

Timozin α1
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 2L9I, 2MNQ
Identifikatori
Aliasi	PTMA
Vanjski ID-jevi	OMIM: 188390 MGI: 97803 HomoloGene: 136511 GeneCards: PTMA
Lokacija gena (čovjek) Hrom. Hromosom 2 (čovjek)[1] Bend 2q37.1 Početak 231,706,895 bp[1] Kraj 231,713,551 bp[1]
Lokacija gena (miš) Hrom. Hromosom 1 (miš)[2] Bend 1|1 C5 Početak 86,526,726 bp[2] Kraj 86,530,712 bp[2]
Ontologija gena Molekularna funkcija • GO:0001948, GO:0016582 vezivanje za proteine • GO:0031493 histone binding Ćelijska komponenta • nukleoplazma • citosol • jedro Biološki proces • transcription, DNA-templated • GO:0035042 histone exchange • negative regulation of apoptotic process Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	5757	19231
Ensembl	ENSG00000187514	ENSMUSG00000026238
UniProt	P06454	P26350
RefSeq (mRNK)	NM_001099285 NM_002823	NM_008972
RefSeq (bjelančevina)	NP_001092755 NP_002814	NP_032998 NP_001347759 NP_001347760
Lokacija (UCSC)	Chr 2: 231.71 – 231.71 Mb	Chr 1: 86.53 – 86.53 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Timozin α₁ je peptidni fragment koji je izveden od protimozina alfa, proteina kojeg kod čovjeka kodira gen PTMA.^[5]

To je bio prvi od peptida iz frakcije timozina 5 koji je u potpunosti sekvenciran i sintetiziran. Za razliku od β-timozina, s kojim genetički i hemijski nije povezan, timozin α₁ nastaje kao fragment od 28 aminokiselina, iz dužeg prethodnika, sa 113 aminokiselina, protimozina α.^[6]

Funkcija

Vjeruje se da je timozin α₁ glavna komponenta timozinske frakcije 5, koja je odgovorna za aktivnost tog pripravka u obnavljanju imunske funkcije kod životinja kojima nedostaje timusna žlijezda. Utvrđeno je da pojačava ćelijski posredovanu imunost, kod ljudi kao i kod pokusnih životinja.^[7]

Terapijska primjena

Od 2009., timozin α₁ odobren je u 35 nerazvijenih zemalja ili zemalja u razvoju za liječenje hepatitisa B i C, a koristi se i za pojačavanje imunskog odgovora u liječenju drugih bolesti.^[8][9]

Kliničke studije

Klinička ispitivanja sugeriraju da bi mogao biti koristan u liječenju [[cistična fibroza| cistične fibroze, septičkog šoka, akutnog respiratornog distres sindroma, peritonitisa, akutne infekcije citomegalovirusom, TBC, teškog akutnog respiratornog sindroma i plućne infekcije kod kritično bolesnih pacijenata^[9] i hroničnog hepatitisa B.^[10]

Proučavan je za moguću upotrebu u liječenju karcinoma (npr. emoterapijom).^[11]

Također pogledajte

• Timozin

Reference

1. GRCh38: Ensembl release 89: ENSG00000187514 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026238 - 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.
5. Manrow RE, Leone A, Krug MS, Eschenfeldt WH, Berger SL (Jul 1992). "The human prothymosin alpha gene family contains several processed pseudogenes lacking deleterious lesions" (PDF). Genomics. 13 (2): 319–31. doi:10.1016/0888-7543(92)90248-Q. PMID 1612591.
6. Garaci E (septembar 2007). "Thymosin alpha1: a historical overview". Ann. N. Y. Acad. Sci. 1112: 14–20. doi:10.1196/annals.1415.039. PMID 17567941.
7. Wara DW, Goldstein AL, Doyle NE, Ammann AJ (januar 1975). "Thymosin activity in patients with cellular immunodeficiency". N. Engl. J. Med. 292 (2): 70–4. doi:10.1056/NEJM197501092920204. PMID 1078552.
8. Garaci E, Favalli C, Pica F, et al. (septembar 2007). "Thymosin alpha 1: from bench to bedside". Ann. N. Y. Acad. Sci. 1112: 225–34. doi:10.1196/annals.1415.044. PMID 17600290.
9. Goldstein AL, Goldstein AL (maj 2009). "From lab to bedside: emerging clinical applications of thymosin alpha 1". Expert Opin Biol Ther. 9 (5): 593–608. doi:10.1517/14712590902911412. PMID 19392576.
10. Wu X, Jia J, You H (2015). "Thymosin alpha-1 treatment in chronic hepatitis B". Expert Opinion on Biological Therapy. 15: 129–132. doi:10.1517/14712598.2015.1007948.
11. Garaci E, Pica F, Rasi G, Favalli C (2000). "Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application". Int J Immunopharmacol. 22: 1067–76. PMID 11137613.

Dopunska literatura

• Martini PG, Katzenellenbogen BS (2003). "Modulation of estrogen receptor activity by selective coregulators". J. Steroid Biochem. Mol. Biol. 85 (2–5): 117–22. doi:10.1016/S0960-0760(03)00207-3. PMID 12943695.
• Barcia MG, Castro JM, Jullien CD, et al. (1992). "Prothymosin alpha is phosphorylated by casein kinase-2". FEBS Lett. 312 (2–3): 152–6. doi:10.1016/0014-5793(92)80924-6. PMID 1426245.
• Baxevanis CN, Thanos D, Reclos GJ, et al. (1992). "Prothymosin alpha enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation". J. Immunol. 148 (7): 1979–84. PMID 1545115.
• Gallego R, Rosón E, García-Caballero T, et al. (1992). "Prothymosin alpha expression in lymph nodes and tonsils: an optical and ultrastructural study". Acta Anat (Basel). 143 (3): 219–22. doi:10.1159/000147251. PMID 1632187.
• Cordero OJ, Sarandeses CS, López JL, et al. (1992). "Prothymosin alpha enhances interleukin 2 receptor expression in normal human T-lymphocytes". Int. J. Immunopharmacol. 13 (8): 1059–65. doi:10.1016/0192-0561(91)90156-2. PMID 1814846.
• Watts JD, Cary PD, Sautiere P, Crane-Robinson C (1990). "Thymosins: both nuclear and cytoplasmic proteins". Eur. J. Biochem. 192 (3): 643–51. doi:10.1111/j.1432-1033.1990.tb19271.x. PMID 2209614.
• Eschenfeldt WH, Manrow RE, Krug MS, Berger SL (1989). "Isolation and partial sequencing of the human prothymosin alpha gene family. Evidence against export of the gene products". J. Biol. Chem. 264 (13): 7546–55. PMID 2708378.
• Gómez-Márquez J, Segade F, Dosil M, et al. (1989). "The expression of prothymosin alpha gene in T lymphocytes and leukemic lymphoid cells is tied to lymphocyte proliferation". J. Biol. Chem. 264 (15): 8451–4. PMID 2785990.
• Goodall GJ, Dominguez F, Horecker BL (1987). "Molecular cloning of cDNA for human prothymosin alpha". Proc. Natl. Acad. Sci. U.S.A. 83 (23): 8926–8. doi:10.1073/pnas.83.23.8926. PMC 387046. PMID 3466166.
• Eschenfeldt WH, Berger SL (1987). "The human prothymosin alpha gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA". Proc. Natl. Acad. Sci. U.S.A. 83 (24): 9403–7. doi:10.1073/pnas.83.24.9403. PMC 387146. PMID 3467312.
• Panneerselvam C, Haritos AA, Caldarella J, Horecker BL (1987). "Prothymosin alpha in human blood". Proc. Natl. Acad. Sci. U.S.A. 84 (13): 4465–9. doi:10.1073/pnas.84.13.4465. PMC 305110. PMID 3474615.
• Pan LX, Haritos AA, Wideman J, et al. (1986). "Human prothymosin alpha: amino acid sequence and immunologic properties". Arch. Biochem. Biophys. 250 (1): 197–201. doi:10.1016/0003-9861(86)90717-4. PMID 3532956.
• Kubota S, Adachi Y, Copeland TD, Oroszlan S (1995). "Binding of human prothymosin alpha to the leucine-motif/activation domains of HTLV-I Rex and HIV-1 Rev". Eur. J. Biochem. 233 (1): 48–54. doi:10.1111/j.1432-1033.1995.048_1.x. PMID 7588773.
• Garcia-Caballero T, Dominguez F, Roson E, et al. (1994). "Distribution of prothymosin alpha in rat and human adrenal cortex". Anat. Rec. 239 (1): 88–94. doi:10.1002/ar.1092390110. PMID 7913591.
• Szabo P, Panneerselvam C, Clinton M, et al. (1993). "Prothymosin alpha gene in humans: organization of its promoter region and localization to chromosome 2". Hum. Genet. 90 (6): 629–34. doi:10.1007/BF00202480. PMID 7916742.
• Maruyama K, Sugano S (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.
• Tsitsiloni OE, Stiakakis J, Koutselinis A, et al. (1993). "Expression of alpha-thymosins in human tissues in normal and abnormal growth". Proc. Natl. Acad. Sci. U.S.A. 90 (20): 9504–7. doi:10.1073/pnas.90.20.9504. PMC 47597. PMID 8415730.
• Sburlati AR, De La Rosa A, Batey DW, et al. (1993). "Phosphorylation of human and bovine prothymosin alpha in vivo". Biochemistry. 32 (17): 4587–96. doi:10.1021/bi00068a015. PMID 8485135.
• Rubtsov IuP; Vartapetian AB (1996). "[New intronless members of human prothymosin alpha genes]". Mol. Biol. (Mosk.). 29 (6): 1320–5. PMID 8592501.

Vanjski linkovi