PTTG1 (pituitary tumor-transforming 1)

Identity

Other names	EAP1
	HPTTG
	MGC126883
	MGC138276
	PTTG
	SECURIN
	Securin
	TUTR1
	hPTTG
Hugo	PTTG1
Location	5q35

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

	The ClustalW alignment of human PTTG isoforms protein sequences.

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
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.

External links

	Nomenclature
Hugo	PTTG1
GDB	PTTG1
Entrez_Gene	PTTG1  9232  pituitary tumor-transforming 1
	Cards
Atlas	PTTG1ID41943ch5q35
GeneCards	PTTG1
Ensembl	PTTG1 [Search_View]   ENSG00000164611 [Gene_View]
Genatlas	PTTG1
GeneLynx	PTTG1
eGenome	PTTG1
euGene	9232
	Genomic and cartography
GoldenPath	PTTG1  -  5q35   chr5:159781443-159788323 +  5q35.1   [Description]    (hg18-Mar_2006)
Ensembl	PTTG1 - 5q35.1 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	PTTG1
	Gene and transcription
Genbank	AF062649 [ ENTREZ ]
Genbank	AF075242 [ ENTREZ ]
Genbank	AF095287 [ ENTREZ ]
Genbank	AJ223953 [ ENTREZ ]
Genbank	BC026003 [ ENTREZ ]
RefSeq	NM_004219 [ SRS ]    NM_004219 [ ENTREZ ]
RefSeq	AC_000048 [ SRS ]    AC_000048 [ ENTREZ ]
RefSeq	NC_000005 [ SRS ]    NC_000005 [ ENTREZ ]
RefSeq	NT_023133 [ SRS ]    NT_023133 [ ENTREZ ]
RefSeq	NW_922784 [ SRS ]    NW_922784 [ ENTREZ ]
AceView	PTTG1 AceView - NCBI
Unigene	Hs.350966 [ SRS ]    Hs.350966 [ NCBI ]     HS350966 [ spliceNest ]
Fast-db	12715 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O95997 [ SRS]    O95997 [ EXPASY ]     O95997 [ INTERPRO ]
Interpro	IPR006940 Securin [ SRS ]    IPR006940 Securin [ EBI ]
CluSTr	O95997
Pfam	PF04856 Securin [ SRS ]    PF04856 Securin [ Sanger ]    pfam04856 [ NCBI-CDD ]
Blocks	O95997
HPRD	04998
	Protein Interaction databases
DIP	O95997
IntAct	O95997
	Polymorphism : SNP, mutations, diseases
OMIM	604147    [ map ]
GENECLINICS	604147
SNP	PTTG1 [dbSNP-NCBI]
SNP	NM_004219 [SNP-NCI]
SNP	PTTG1 [GeneSNPs - Utah]  PTTG1] [HGBASE - SRS]
HAPMAP	PTTG1 [HAPMAP]
COSMIC	PTTG1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	PTTG1
	General knowledge
Family Browser	PTTG1 [UCSC Family Browser]
SOURCE	NM_004219
SMD	Hs.350966
SAGE	Hs.350966
GO	molecular_function [Amigo]  molecular_function
GO	transcription factor activity [Amigo]  transcription factor activity
GO	cysteine protease inhibitor activity [Amigo]  cysteine protease inhibitor activity
GO	protein binding [Amigo]  protein binding
GO	cellular_component [Amigo]  cellular_component
GO	nucleus [Amigo]  nucleus
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	cytoplasm [Amigo]  cytoplasm
GO	DNA metabolic process [Amigo]  DNA metabolic process
GO	DNA repair [Amigo]  DNA repair
GO	transcription from RNA polymerase II promoter [Amigo]  transcription from RNA polymerase II promoter
GO	cell cycle [Amigo]  cell cycle
GO	chromosome segregation [Amigo]  chromosome segregation
GO	mitosis [Amigo]  mitosis
GO	spermatogenesis [Amigo]  spermatogenesis
GO	chromosome organization and biogenesis [Amigo]  chromosome organization and biogenesis
GO	cell division [Amigo]  cell division
KEGG	Cell cycle
PubGene	PTTG1
TreeFam	PTTG1
CTD	9232 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	PTTG1 Related clones (RZPD - Berlin)
	PubMed
PubMed	61 Pubmed reference(s) in LocusLink

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 articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	03-2008	Siva 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. March 2008 . URL : http://AtlasGeneticsOncology.org/Genes/PTTG1ID41943ch5q35.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:26:25 2008