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MGP003835

UniProt Annotations

Entry Information

Gene Name	pituitary tumor-transforming 1
Protein Entry	PTTG1_HUMAN
UniProt ID	O95997
Species	Human

Comments

Comment type	Description
Developmental Stage	Low level during G1 and S phases. Peaks at M phase. During anaphase, it is degraded.
Domain	The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway. {ECO:0000250}.
Domain	The TEK-boxes are required for 'Lys-11'-linked ubiquitination and facilitate the transfer of the first ubiquitin and ubiquitin chain nucleation. TEK-boxes may direct a catalytically competent orientation of the UBE2C/UBCH10-ubiquitin thioester with the acceptor lysine residue. {ECO:0000269\|PubMed:18485873}.
Function	Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of TP53. The negative regulation of TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation. {ECO:0000269\|PubMed:10411507, ECO:0000269\|PubMed:11238996, ECO:0000269\|PubMed:11371342, ECO:0000269\|PubMed:12355087}.
Ptm	Phosphorylated at Ser-165 by CDK1 during mitosis. {ECO:0000269\|PubMed:10656688}.
Ptm	Phosphorylated in vitro by ds-DNA kinase. {ECO:0000269\|PubMed:10656688}.
Ptm	Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties by the anaphase promoting complex (APC) at the onset of anaphase, conducting to its degradation. 'Lys-11'-linked ubiquitination is mediated by the E2 ligase UBE2C/UBCH10. {ECO:0000269\|PubMed:10411507, ECO:0000269\|PubMed:18485873}.
Similarity	Belongs to the securin family. {ECO:0000305}.
Subcellular Location	Cytoplasm. Nucleus.
Subunit	Interacts with RPS10 and DNAJA1 (By similarity). Interacts with the caspase-like ESPL1, and prevents its protease activity probably by covering its active site. Interacts with TP53 and blocks its activity probably by blocking its binding to DNA. Interacts with the Ku 70 kDa subunit of ds-DNA kinase. Interacts with PTTG1IP. {ECO:0000250, ECO:0000269\|PubMed:10411507, ECO:0000269\|PubMed:10781616, ECO:0000269\|PubMed:11238996, ECO:0000269\|PubMed:12355087}.
Tissue Specificity	Expressed at low level in most tissues, except in adult testis, where it is highly expressed. Overexpressed in many patients suffering from pituitary adenomas, primary epithelial neoplasias, and esophageal cancer. {ECO:0000269\|PubMed:9811450}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PTTG1ID41943ch5q35.html";