Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

PTTG1 (pituitary tumor-transforming 1)

Identity

Other namesEAP1
HPTTG
MGC126883
MGC138276
PTTG
SECURIN
Securin
TUTR1
hPTTG
HGNC (Hugo) PTTG1
LocusID (NCBI) 9232
Location 5q33.3
Location_base_pair Starts at 159848917 and ends at 159855751 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

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.
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.

Protein

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
 
  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 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 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.
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945

External links

Nomenclature
HGNC (Hugo)PTTG1   9690
Cards
AtlasPTTG1ID41943ch5q35
Entrez_Gene (NCBI)PTTG1  9232  pituitary tumor-transforming 1
GeneCards (Weizmann)PTTG1
Ensembl (Hinxton)ENSG00000164611 [Gene_View]  chr5:159848917-159855751 [Contig_View]  PTTG1 [Vega]
ICGC DataPortalENSG00000164611
AceView (NCBI)PTTG1
Genatlas (Paris)PTTG1
WikiGenes9232
SOURCE (Princeton)NM_001282382 NM_001282383 NM_004219
Genomic and cartography
GoldenPath (UCSC)PTTG1  -  5q33.3   chr5:159848917-159855751 +  5q35.1   [Description]    (hg19-Feb_2009)
EnsemblPTTG1 - 5q35.1 [CytoView]
Mapping of homologs : NCBIPTTG1 [Mapview]
OMIM604147   
Gene and transcription
Genbank (Entrez)AF062649 AF075242 AF095287 AJ223953 AK312209
RefSeq transcript (Entrez)NM_001282382 NM_001282383 NM_004219
RefSeq genomic (Entrez)AC_000137 NC_000005 NC_018916 NT_023133 NW_001838954 NW_004929325
Consensus coding sequences : CCDS (NCBI)PTTG1
Cluster EST : UnigeneHs.350966 [ NCBI ]
CGAP (NCI)Hs.350966
Alternative Splicing : Fast-db (Paris)GSHG0024426
Alternative Splicing GalleryENSG00000164611
Gene ExpressionPTTG1 [ NCBI-GEO ]     PTTG1 [ SEEK ]   PTTG1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95997 (Uniprot)
NextProtO95997  [Medical]
With graphics : InterProO95997
Splice isoforms : SwissVarO95997 (Swissvar)
Domains : Interpro (EBI)Securin_separation-inh_met    Securin_separation_inhibitor   
Related proteins : CluSTrO95997
Domain families : Pfam (Sanger)Securin (PF04856)   
Domain families : Pfam (NCBI)pfam04856   
DMDM Disease mutations9232
Blocks (Seattle)O95997
Human Protein AtlasENSG00000164611
Peptide AtlasO95997
HPRD04998
IPIIPI00003494   IPI00383627   IPI00974116   
Protein Interaction databases
DIP (DOE-UCLA)O95997
IntAct (EBI)O95997
FunCoupENSG00000164611
BioGRIDPTTG1
IntegromeDBPTTG1
STRING (EMBL)PTTG1
Ontologies - Pathways
QuickGOO95997
Ontology : AmiGOmitotic cell cycle  sequence-specific DNA binding transcription factor activity  cysteine-type endopeptidase inhibitor activity  protein binding  nucleus  cytoplasm  cytosol  DNA repair  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  chromosome segregation  mitotic nuclear division  spermatogenesis  negative regulation of endopeptidase activity  SH3 domain binding  anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process  chromosome organization  
Ontology : EGO-EBImitotic cell cycle  sequence-specific DNA binding transcription factor activity  cysteine-type endopeptidase inhibitor activity  protein binding  nucleus  cytoplasm  cytosol  DNA repair  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  chromosome segregation  mitotic nuclear division  spermatogenesis  negative regulation of endopeptidase activity  SH3 domain binding  anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process  chromosome organization  
Pathways : KEGGCell cycle    Oocyte meiosis    HTLV-I infection   
REACTOMEO95997 [protein]
REACTOME PathwaysREACT_115566 Cell Cycle [pathway]
REACTOME PathwaysREACT_21300 Mitotic M-M/G1 phases [pathway]
Protein Interaction DatabasePTTG1
Wikipedia pathwaysPTTG1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)PTTG1
SNP (GeneSNP Utah)PTTG1
SNP : HGBasePTTG1
Genetic variants : HAPMAPPTTG1
1000_GenomesPTTG1 
ICGC programENSG00000164611 
CONAN: Copy Number AnalysisPTTG1 
Somatic Mutations in Cancer : COSMICPTTG1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DECIPHER (Syndromes)5:159848917-159855751
Mutations and Diseases : HGMDPTTG1
OMIM604147   
MedgenPTTG1
GENETestsPTTG1
Disease Genetic AssociationPTTG1
Huge Navigator PTTG1 [HugePedia]  PTTG1 [HugeCancerGEM]
Genomic VariantsPTTG1  PTTG1 [DGVbeta]
Exome VariantPTTG1
dbVarPTTG1
ClinVarPTTG1
snp3D : Map Gene to Disease9232
DGIdb (Curated mutations)PTTG1
DGIdb (Drug Gene Interaction db)PTTG1
General knowledge
Homologs : HomoloGenePTTG1
Homology/Alignments : Family Browser (UCSC)PTTG1
Phylogenetic Trees/Animal Genes : TreeFamPTTG1
Chemical/Protein Interactions : CTD9232
Chemical/Pharm GKB GenePA34033
Clinical trialPTTG1
Cancer Resource (Charite)ENSG00000164611
Other databases
Probes
Litterature
PubMed172 Pubmed reference(s) in Entrez
CoreMinePTTG1
GoPubMedPTTG1
iHOPPTTG1

Bibliography

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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written03-2008Siva Kumar Panguluri, Sham S Kakar
Department of Medicine and James Graham Brown Cancer Center, University of Louisville KY 40202, USA

Citation

This paper should be referenced as such :
Panguluri, SK ; Kakar, SS
PTTG1 (pituitary tumor-transforming 1)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(1):43-46.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/PTTG1ID41943ch5q35.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Dec 4 15:13:35 CET 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.