PTTG1 (pituitary tumor-transforming 1)

2008-03-01   Siva Kumar Panguluri  , Sham S Kakar  

Department of Medicine, James Graham Brown Cancer Center, University of Louisville KY 40202, USA

Identity

HGNC
PTTG1
LOCATION
5q33.3
LOCUSID
9232
ALIAS
EAP1,HPTTG,PTTG,TUTR1

DNA/RNA

Note

The encoded protein is a homolog of yeast securin proteins, which prevent separins from promoting sister chromatid separation.
Atlas Image
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.

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.

Proteins

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.

WavelengthMolar Extinction w/o DisulfidesMolar Extinction w/ All Disulfides
27884008527
27983508470
28082508370
28280008100

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.

WavelengthMolar Extinction w/o DisulfidesMolar Extinction w/ All Disulfides
2780.35680.3622
2790.35460.3597
2800.35040.3555
2820.33980.3440
Atlas Image
The ClustalW alignment of human PTTG isoforms protein sequences.

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.

Mutations

Note

See Figure 3

Implicated in

Entity name
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.
Entity name
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.

Article Bibliography

Pubmed IDLast YearTitleAuthors
171496952007Pituitary tumor transforming gene: an important gene in normal cellular functions and tumorigenesis.Bradshaw C et al
179281332007The emerging role of pituitary tumour transforming gene (PTTG) in endocrine tumourigenesis.Kim DS et al
173253392007Pituitary tumor-transforming gene: physiology and implications for tumorigenesis.Vlotides G et al

Other Information

Locus ID:

NCBI: 9232
MIM: 604147
HGNC: 9690
Ensembl: ENSG00000164611

Variants:

dbSNP: 9232
ClinVar: 9232
TCGA: ENSG00000164611
COSMIC: PTTG1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000164611ENST00000352433O95997
ENSG00000164611ENST00000352433Q6IAL9
ENSG00000164611ENST00000393964O95997
ENSG00000164611ENST00000393964Q6IAL9
ENSG00000164611ENST00000517480E5RJR4
ENSG00000164611ENST00000520452O95997
ENSG00000164611ENST00000520452Q6IAL9

Expression (GTEx)

0
50
100
150
200
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Cell cycleKEGGko04110
Cell cycleKEGGhsa04110
Oocyte meiosisKEGGko04114
Oocyte meiosisKEGGhsa04114
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
M PhaseREACTOMER-HSA-68886
Mitotic Metaphase and AnaphaseREACTOMER-HSA-2555396
Mitotic AnaphaseREACTOMER-HSA-68882
Separation of Sister ChromatidsREACTOMER-HSA-2467813
Regulation of mitotic cell cycleREACTOMER-HSA-453276
APC/C-mediated degradation of cell cycle proteinsREACTOMER-HSA-174143
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteinsREACTOMER-HSA-176814
APC/C:Cdc20 mediated degradation of mitotic proteinsREACTOMER-HSA-176409
APC/C:Cdc20 mediated degradation of SecurinREACTOMER-HSA-174154
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1REACTOMER-HSA-174178

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
364145142024Pituitary tumor transforming gene 1 promotes proliferation and malignant phenotype in osteosarcoma via NF-κB signaling.0
384208102024Multi-Omics Analysis of the Oncogenic Value of Pituitary Tumor-Transforming Gene 1 (PTTG1) in Human Cancers.0
364145142024Pituitary tumor transforming gene 1 promotes proliferation and malignant phenotype in osteosarcoma via NF-κB signaling.0
384208102024Multi-Omics Analysis of the Oncogenic Value of Pituitary Tumor-Transforming Gene 1 (PTTG1) in Human Cancers.0
374005292023Phosphorylated PTTG1 switches its subcellular distribution and promotes β-catenin stabilization and subsequent transcription activity.4
380692142023SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma.0
374005292023Phosphorylated PTTG1 switches its subcellular distribution and promotes β-catenin stabilization and subsequent transcription activity.4
380692142023SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma.0
331481012022miR-362-3p suppresses sinonasal squamous cell carcinoma progression via directly targeting pituitary tumor-transforming gene 1.3
350505502022The pituitary tumour-transforming gene 1/delta-like homologue 1 pathway plays a key role in liver fibrogenesis.4
352342602022miR‑374c‑5p regulates PTTG1 and inhibits cell growth and metastasis in hepatocellular carcinoma by regulating epithelial‑mesenchymal transition.4
357306252022SIRT1 suppresses pituitary tumor progression by downregulating PTTG1 expression.2
357688322022Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer.1
331481012022miR-362-3p suppresses sinonasal squamous cell carcinoma progression via directly targeting pituitary tumor-transforming gene 1.3
350505502022The pituitary tumour-transforming gene 1/delta-like homologue 1 pathway plays a key role in liver fibrogenesis.4

Citation

Siva Kumar Panguluri ; Sham S Kakar

PTTG1 (pituitary tumor-transforming 1)

Atlas Genet Cytogenet Oncol Haematol. 2008-03-01

Online version: http://atlasgeneticsoncology.org/gene/41943/case-report-explorer/favicon/js/web-card-_common.js