P97613 (PTTG1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 88. History...
Names and origin
|Protein names||Recommended name:|
Pituitary tumor-transforming gene 1 protein
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||199 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 p53/TP53. The negative regulation of p53/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 By similarity.
Interacts with the caspase-like ESPL1, and prevents its protease activity by covering its active site. Interacts with p53/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 By similarity. Interacts with RPS10 and DNAJA1. Ref.3
The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway By similarity.
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 By similarity.
Phosphorylated at Ser-162 by CDK1 during mitosis By similarity.
Phosphorylated in vitro by ds-DNA kinase By similarity.
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 By similarity.
|Involvement in disease|
Has strong transforming capabilities on a variety of cell lines including NIH 3T3 fibroblasts and on athymic nude mice. Overexpressed in animals suffering from pituitary adenomas. The transforming capability may be due to its interaction and regulation of p53/TP53 pathway. Ref.1
Belongs to the securin family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 199||198||Securin||PRO_0000206364|
|Motif||58 – 61||4||D-box|
|Motif||68 – 70||3||TEK-box 1|
|Motif||91 – 93||3||TEK-box 2|
|Motif||179 – 192||14||SH3-binding|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine By similarity|
|Modified residue||162||1||Phosphoserine; by CDK1 By similarity|
|||"Isolation and characterization of a pituitary tumor-transforming gene (PTTG)."|
Pei L., Melmed S.
Mol. Endocrinol. 11:433-441(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DISEASE.
Tissue: Pituitary tumor.
|||"Genomic organization and identification of an enhancer element containing binding sites for multiple proteins in rat pituitary tumor-transforming gene."|
J. Biol. Chem. 273:5219-5225(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
|||"Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells."|
J. Biol. Chem. 274:3151-3158(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INTERACTION WITH RPS10 AND DNAJA1.
|+||Additional computationally mapped references.|
|U73030 mRNA. Translation: AAB47974.1.|
AF021802 Genomic DNA. Translation: AAC40036.1.
|RefSeq||NP_071786.1. NM_022391.2. |
3D structure databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000005070; ENSRNOP00000005070; ENSRNOG00000003802. |
|UCSC||RGD:68359. rat. |
|RGD||68359. Pttg1. |
Gene expression databases
Family and domain databases
|InterPro||IPR018008. Securin_separation-inh_met. |
|PANTHER||PTHR10418. PTHR10418. 1 hit. |
|Pfam||PF04856. Securin. 1 hit. |
|Accession||Primary (citable) accession number: P97613|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families