PTTG1
Identifiers
AliasesPTTG1, EAP1, HPTTG, PTTG, TUTR1, pituitary tumor-transforming 1, PTTG1 regulator of sister chromatid separation, securin, ECRAR
External IDsOMIM: 604147 MGI: 1353578 HomoloGene: 3110 GeneCards: PTTG1
Orthologs
SpeciesHumanMouse
Entrez

9232

30939

Ensembl

ENSG00000164611

ENSMUSG00000020415

UniProt

O95997
Q6IAL9

Q9CQJ7

RefSeq (mRNA)

NM_004219
NM_001282382
NM_001282383

NM_001131054
NM_013917
NM_001362799

RefSeq (protein)

NP_001124526
NP_038945
NP_001349728

Location (UCSC)Chr 5: 160.42 – 160.43 MbChr 11: 43.31 – 43.32 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Securin is a protein that in humans is encoded by the PTTG1 gene.[5][6][7]

Function

The encoded protein is a homolog of yeast securin proteins, which prevent separins from promoting sister chromatid separation. It is an anaphase-promoting complex (APC) substrate that associates with a separin until activation of the APC. The gene product has transforming activity in vitro and tumorigenic activity in vivo, and the gene is highly expressed in various 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. The gene product is mainly a cytosolic protein, although it partially localizes in the nucleus.[7]

Interactions

PTTG1 has been shown to interact with:

Regulation

During Mitosis CDK1 phosphorylate PTTG1 at Ser-165.[12] PTTG1 is down-regulated in melanoma cells in response to the cyclin-dependent kinase inhibitor PHA-848125.[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164611 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020415 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Domínguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, Pintor-Toro JA (Oct 1998). "hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG". Oncogene. 17 (17): 2187–93. doi:10.1038/sj.onc.1202140. PMID 9811450. S2CID 24151303.
  6. ^ Zhang X, Horwitz GA, Prezant TR, Valentini A, Nakashima M, Bronstein MD, Melmed S (Jan 1999). "Structure, expression, and function of human pituitary tumor-transforming gene (PTTG)". Molecular Endocrinology. 13 (1): 156–66. doi:10.1210/me.13.1.156. PMID 9892021.
  7. ^ a b "Entrez Gene: PTTG1 pituitary tumor-transforming 1".
  8. ^ a b Pei L (Jan 1999). "Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells". The Journal of Biological Chemistry. 274 (5): 3151–8. doi:10.1074/jbc.274.5.3151. PMID 9915854.
  9. ^ Romero F, Multon MC, Ramos-Morales F, Domínguez A, Bernal JA, Pintor-Toro JA, Tortolero M (Mar 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Research. 29 (6): 1300–7. doi:10.1093/nar/29.6.1300. PMC 29753. PMID 11238996.
  10. ^ Bernal JA, Luna R, Espina A, Lázaro I, Ramos-Morales F, Romero F, Arias C, Silva A, Tortolero M, Pintor-Toro JA (Oct 2002). "Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis". Nature Genetics. 32 (2): 306–11. doi:10.1038/ng997. PMID 12355087. S2CID 1770399.
  11. ^ Chien W, Pei L (Jun 2000). "A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product". The Journal of Biological Chemistry. 275 (25): 19422–7. doi:10.1074/jbc.M910105199. PMID 10781616.
  12. ^ Ramos-Morales F, Domínguez A, Romero F, Luna R, Multon MC, Pintor-Toro JA, Tortolero M (Jan 2000). "Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product". Oncogene. 19 (3): 403–9. doi:10.1038/sj.onc.1203320. PMID 10656688. S2CID 21958836.
  13. ^ Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, Del Bufalo D, Desideri M, Bonmassar E, Pfeffer U, D'Atri S (Sep 2012). "Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125". Biochemical Pharmacology. 84 (5): 598–611. doi:10.1016/j.bcp.2012.06.004. PMID 22704958.

Further reading

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