| Note |
The encoded protein is a homolog of yeast securin proteins, which prevent separins from promoting sister chromatid separation. |
| Note | [Annexed document] |
| | Fig 1: ClustalW analysis of Human PTTG isoforms.
Fig 2: ClustalW analysis of PTTG1 in Human, Chimpanzee, Gorilla, Cow, Mouse and Rat.
Fig 3: Neighbor Phyolgenetic tree of human PTTG isoforms.
Fig 4: Neighbor Phyolgenetic tree of Human, Chimpanzee, Gorilla, Cow, Mouse and Rat PTTG1. |
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| Description | This gene has three isoforms in human named as PTTG1, PTTG2 and PTTG3. |
| Transcription | The human PTTG mRNA is 728bp (NM_004219) and cDNA is 609bp. |
| Note | Human PTTG1 protein is of 202 amino acids length which does not have any cysteine.
The molecular weight of this protein is 23544.6797 Da and estimated pI is 6.58. Extinction Coefficient:
Extinction coefficient estimated by the method of Gill and von Hippel (Analytical Biochemistry, 182: 319-326, 1989) where lyophilized proteins were used to establish an absorbance curve based on the number of tyrptophans, tyrosines, and disulfide bonds. Units are in M-1 cm-1.
Wavelength | Molar Extinction w/o Disulfides | Molar Extinction w/ All Disulfides | 278 | 8400 | 8527 | 279 | 8350 | 8470 | 280 | 8250 | 8370 | 282 | 8000 | 8100 | Extinction Coefficient:
Extinction coefficient estimated by the method of Gill and von Hippel (Analytical Biochemistry, 182: 319-326, 1989) where lyophilized proteins were used to establish an absorbance curve based on the number of tyrptophans, tyrosines, and disulfide bonds. Units are in (mg/mL)-1 cm-1.
Wavelength | Molar Extinction w/o Disulfides | Molar Extinction w/ All Disulfides | 278 | 0.3568 | 0.3622 | 279 | 0.3546 | 0.3597 | 280 | 0.3504 | 0.3555 | 282 | 0.3398 | 0.3440 | |
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| | The ClustalW alignment of human PTTG isoforms protein sequences. |
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| Description | Human PTTG1 protein is of 202 amino acids length which does not have any cysteine.
The molecular weight of this protein is 23544.6797 Da and estimated pI is 6.58. |
| Expression | The PTTG protein is overexpressed in many endocrine-related tumors including pituitary, thyroid, breast, ovarian, and uterine. The elevated expressions of this protein were also observed in nonendocrine-related cancers including the central nervous, pulmonary, and gastrointestinal systems. |
| Localisation | The gene product is mainly a cytosolic protein, although it partially localizes in the nucleus. |
| Function | The PTTG protein prevent separins from promoting sister chromatid separation. During metaphase, the sister chromatids are held together by a complex of four proteins called "cohesion". The separases cleaves this complex during onset of anaphase. The separase proteolytic activity is inhibited by this PTTG protein in most of the cell cycle. During metaphase to anaphase transition, the anaphase-promoting complex (APC) binds to PTTG and cause proteolytic degradation and thereby separases activation, which in turn mediates sister-chromatid separation. This PTTG gene product has transforming activity in vitro and tumorigenic activity in vivo, and the gene is highly expressed in all most all tumors. The gene product contains 2 PXXP motifs, which are required for its transforming and tumorigenic activities, as well as for its stimulation of basic fibroblast growth factor expression. It also contains a destruction box (D box) that is required for its degradation by the APC. The acidic C-terminal region of the encoded protein can act as a transactivation domain. |
| Entity | Cancer |
| Note | Securin at its normal cellular function inhibits the sister-chromatids to separate until the late anaphase. During anaphase, the Securin will be cleaved by Anaphase Promoting Complex (APC), which activated Separins and there by sister-chromatid separation. The failure of this process cause incomplete sister-chromatid separation and cause aneuploidy.
The PTTG is found to be expressed in higher levels in several tumors including pituitary, thyroid, colon, ovary, testis, lung and breast. Overexpressions of PTTG enhance cell proliferation, induce cellular transformation and promote tumor formation in vitro, and in vivo. The mechanism of PTTG to induce cell transformation is still not completely understood.
Recently we showed that the human Pituitary tumor transforming gene (PTTG) regulates angiogenesis and invasion through increased expression and secretion of matrix metalloproteinase-2 (MMP-2). We also found overexpression of many growth factors like TGF-beta, bFGF, VEGF and integrins. The role of PTTG in regulating metastatic potential in cancer cells is under investigation. |
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| Entity | Type 2 Diabetes |
| Note | The role of this gene in cell proliferation makes it very essential for many other physiological functions. The overexpression of this gene found to down-regulate Hexokinase-2, an important gene for Glycolysis, Fructose, Mannose, Galactose, Sucrose and Starch metabolism (Un-published data). The down regulation of Hexokinase can cause Type 2 diabetes. The PTTG knockout mice showed reduction in islets size in the pancreas when compared to the normal animal suggesting its role in islets development. |
| Prognosis | The knockout of PTTG1 in vitro in many cancer cell lines showed decreased cell proliferation, cell migration, cell invasion and colony formation, suggesting that the siRNA mediated knockout of this gene specifically to the cancer cells can be a good choice for targeted cancer therapy. |
| Oncogenesis | The over expression of this gene was found in several tumors. The recent data suggest that the PTTG regulates c-myc and increase cell proliferation. There are also reports that the p53 binds to the PTTG regulatory elements. We have reported that the PTTG regulates cell proliferation by overexpressing MMP-2. We also found the up-regulation of growth factors like bFGF, VEGF, TGF-beta and integrins. |
| | |
| Pituitary tumor transforming gene: an important gene in normal cellular functions and tumorigenesis. |
| Bradshaw C, Kakar SS. |
| Histol Histopathol. 2007 Feb;22(2):219-26. Review. |
| PMID 17149695 |
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| The emerging role of pituitary tumour transforming gene (PTTG) in endocrine tumourigenesis. |
| Kim DS, Fong J, Read ML, McCabe CJ. |
| Mol Cell Endocrinol. 2007 Nov 15;278(1-2):1-6. Epub 2007 Aug 28. Review. |
| PMID 17928133 |
| |
| Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. |
| Vlotides G, Eigler T, Melmed S. |
| Endocr Rev. 2007 Apr;28(2):165-86. Epub 2007 Feb 26. Review. |
| PMID 17325339 |
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