PIN1

The human PIN1 gene encodes an essential nuclear peptidylprolyl cis-trans isomerase (PPIase; EC 5.2.1.8) involved in regulation of mitosis. PIN1 belongs to a class of PPIases that includes the E. coli parvulin, yeast Ess1, and Drosophila dodo (dod) gene products (Lu et al., 1996 [PubMed 8606777]).[supplied by OMIM

Full Name

peptidylprolyl cis/trans isomerase, NIMA-interacting 1

Function

Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs (PubMed:21497122, PubMed:23623683, PubMed:29686383).
By inducing conformational changes in a subset of phosphorylated proteins, acts as a molecular switch in multiple cellular processes (PubMed:21497122, PubMed:22033920, PubMed:23623683).
Displays a preference for acidic residues located N-terminally to the proline bond to be isomerized. Regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Down-regulates kinase activity of BTK (PubMed:16644721).
Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation (PubMed:15664191).
Binds and targets PML and BCL6 for degradation in a phosphorylation-dependent manner (PubMed:17828269).
Acts as a regulator of JNK cascade by binding to phosphorylated FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation: degradation of FBXW7 leads to subsequent stabilization of JUN (PubMed:22608923).
May facilitate the ubiquitination and proteasomal degradation of RBBP8/CtIP through CUL3/KLHL15 E3 ubiquitin-protein ligase complex, hence favors DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:23623683, PubMed:27561354).
Upon IL33-induced lung inflammation, catalyzes cis-trans isomerization of phosphorylated IRAK3/IRAK-M, inducing IRAK3 stabilization, nuclear translocation and expression of pro-inflammatory genes in dendritic cells (PubMed:29686383).

Biological Process

Cell cycleIEA:UniProtKB-KW
Negative regulation of amyloid-beta formationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of cell motilityManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of protein bindingManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of protein catabolic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Neuron differentiationISS:ParkinsonsUK-UCL
Positive regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of GTPase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of protein bindingManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of protein dephosphorylationManual Assertion Based On ExperimentTAS:ARUK-UCL
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentIGI:MGI
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of ubiquitin-protein transferase activityManual Assertion Based On ExperimentIDA:BHF-UCL
Protein peptidyl-prolyl isomerizationManual Assertion Based On ExperimentIDA:UniProtKB
Protein stabilizationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Regulation of cytokinesisManual Assertion Based On ExperimentIMP:MGI
Regulation of gene expressionManual Assertion Based On ExperimentIDA:ARUK-UCL
Regulation of mitotic nuclear divisionManual Assertion Based On ExperimentTAS:ProtInc
Regulation of pathway-restricted SMAD protein phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of protein localization to nucleusManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:ARUK-UCL
Regulation of protein stabilityManual Assertion Based On ExperimentIMP:UniProtKB
Response to hypoxiaManual Assertion Based On ExperimentIDA:UniProtKB
Synapse organizationISS:ParkinsonsUK-UCL

Cellular Location

Nucleus
Nucleus speckle
Cytoplasm
Colocalizes with NEK6 in the nucleus (PubMed:16476580).
Mainly localized in the nucleus but phosphorylation at Ser-71 by DAPK1 results in inhibition of its nuclear localization (PubMed:21497122).

PTM

Phosphorylation at Ser-71 by DAPK1 results in inhibition of its catalytic activity, nuclear localization, and its ability to induce centrosome amplification, chromosome instability and cell transformation (PubMed:21497122).
Ser-71 is dephosphorylated upon IL33-stimulation of dendritic cells (By similarity).