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peptidyl-prolyl cis-trans isomerase NIMA-interacting 1; peptidyl-prolyl cis-trans isomerase Pin1; PPIase Pin1; Rotamase Pin1 (PIN1)

Function: - Pin-1 regulates conformation & function of some phosphorylated proteins including microtubule associated protein tau, & is involved in regulation of mitosis - phosphorylation inactivates pin1 - Pin1 catalyzes prolyl isomerization of specific phospho-Ser/Thr-Pro motifs in [2,4]: - Cdc25C - microtubule associated protein tau - interaction site on tau is phospho-Thr231-Pro232 [7] - NIMA - wee1 - plk1 - myt1 - cdc27 - CENP-F - Incenp - rab4 - bcl-2 - NHERF-1 - KRMP1 - RNA polymerase II - sin3-rpd3 - c-jun - beta-catenin - inhibits interaction with APC - cyclin D1 - both transcriptional & post-translational levels, increases stability & c-jun targeted transcriptional activity of cyclin D1 - DNA damage enhances the interaction of Pin-1 & p53; this is dependent on the WW domain in pin-1 & Ser33/46 in p53 - Pin-1 regulates stability of p53 & its p21 transcriptional activity - loss of pin-1 in vitro results in loss of p53 & p21 responses to DNA damage Expression: - expressed at low levels in most normal tissues - expression is increased with cell proliferation Pathology: - Pin1 expression inversely correlates with neuronal vulnerability & neurofibrillary degeneration in Alzheimer's disease. - Pin1 knockout mice show progressive age dependent neuropathy with motor & behavioral defects, tau hyperphosphorylation, tau filament formation & neurodegeneration [3] - Pin1 is overexpressed in some cancers - breast cancer, prostate cancer, lung cancer, cervical cancer, ovarian cancer, brain tumors, colon cancer, melanoma

Related

PIN1-like protein; peptidylprolyl cis-trans isomerase NIMA-interacting 1 pseudogene 1 (PIN1P1, PIN1L)

General

phosphoprotein peptidyl-prolyl cis/trans isomerase, NIMA-interacting (Pin) peptidyl-prolyl cis/trans isomerase (PPIase) or rotamase

Properties

SIZE: entity length = 163 aa MW = 18 kD COMPARTMENT: cell nucleus MOTIF: WW domain (W/rsp5/WWP domain) {5-39} MOTIF: Ser phosphorylation site {S16} PpiC NAME: PpiC SITE: 52-163 MOTIF: Ser phosphorylation site {S108}

References

  1. Wulf GM et al, Role of Pin1 in the regulation of p53 stability and p21 transactivation, and cell cycle checkpoints in response to DNA damage. J Biol Chem 277:47976-9, 2002 PMID: 11090625 PMID: 12388558
  2. Zhou XZ, Kops O, Werner A, Lu PJ, Shen M, Stoller G, Kullertz G, Stark M, Fischer G, Lu KP. Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins. Mol Cell. 2000 Oct;6(4):873-83. PMID: 11090625
  3. Liou YC et al, Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424:556-60, 2003 PMID: 12891359
  4. Lu KP, Liou YC, Zhou XZ. Pinning down proline-directed phosphorylation signaling. Trends Cell Biol. 2002 Apr;12(4):164-72. Review. PMID: 11978535
  5. Lu KP Prolyl isomerase Pin1 as a molecular target for cancer diagnostics and therapeutics. Cancer Cell. 2003 Sep;4(3):175-80. Review. No abstract available. PMID: 14522251
  6. Entrez Gene :accession 5300
  7. Smet C, Sambo AV, Wieruszeski JM, Leroy A, Landrieu I, Buee L, Lippens G. The peptidyl prolyl cis/trans-isomerase Pin1 recognizes the phospho-Thr212-Pro213 site on Tau Biochemistry 43(7):2032-40, 2004 PMID: 14967043
  8. Bao L, Kimzey A, Sauter G, Sowadski JM, Lu KP, Wang DG. Prevalent overexpression of prolyl isomerase Pin1 in human cancers Am J Pathology 164(5):1727-37, 2004 PMID: 15111319

Databases & Figures

OMIM 601052 UniProt Q13526 PFAM correlations Entrez Gene 5300 Kegg hsa:5300 ENZYME 5.2.1.8 Figures/diagrams/slides/tables related to peptidyl-prolyl cis-trans isomerase NIMA-interacting 1