Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)
The protein contains 163 amino acids for an estimated molecular weight of 18243 Da.
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) (PubMe (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Cell cycle
Cytokine-mediated signaling pathway
Innate immune response
Negative regulation of amyloid-beta formation
Negative regulation of cell motility
Negative regulation of ERK1 and ERK2 cascade
Negative regulation of neuron apoptotic process
Negative regulation of protein binding
Negative regulation of protein catabolic process
Negative regulation of transforming growth factor beta receptor signaling pathway
Negative regulation of type I interferon production
Neuron differentiation
Positive regulation of canonical Wnt signaling pathway
Positive regulation of cell growth involved in cardiac muscle cell development
Positive regulation of GTPase activity
Positive regulation of neuron apoptotic process
Positive regulation of protein binding
Positive regulation of protein dephosphorylation
Positive regulation of protein phosphorylation
Positive regulation of transcription by RNA polymerase II
Positive regulation of ubiquitin-protein transferase activity
Protein peptidyl-prolyl isomerization
Protein stabilization
Regulation of cytokinesis
Regulation of gene expression
Regulation of mitotic nuclear division
Regulation of pathway-restricted SMAD protein phosphorylation
Regulation of protein localization to nucleus
Regulation of protein phosphorylation
Regulation of protein stability
Regulation of signal transduction by p53 class mediator
Response to hypoxia
Synapse organization
Cellular Component
Ciliary basal body
Cytoplasm
Cytosol
Glutamatergic synapse
Midbody
Mitochondrion
Neuron projection
Nuclear speck
Nucleoplasm
Nucleus
Postsynaptic cytosol
Molecular Function
Beta-catenin binding
Cis-trans isomerase activity
GTPase activating protein binding
Mitogen-activated protein kinase kinase binding
Motor activity
Peptidyl-prolyl cis-trans isomerase activity
Phosphoprotein binding
Phosphoserine residue binding
Phosphothreonine residue binding
Tau protein binding
The reference OMIM entry for this protein is 601052
Peptidyl-prolyl cis/trans isomerase, nima-interacting, 1; pin1
Dodo, drosophila, homolog of; dod
DESCRIPTION
Peptidyl-prolyl cis/trans isomerases (PPIases; EC 5.2.1.8), such as PIN1, catalyze the cis/trans isomerization of peptidyl-prolyl peptide bonds. PIN1 is the only PPIase that specifically binds to phosphorylated ser/thr-pro motifs to catalytically regulate the post-phosphorylation conformation of its substrates. PIN1-catalyzed conformational regulation has a profound impact on key proteins involved in the regulation of cell growth, genotoxic and other stress responses, the immune response, germ cell development, neuronal differentiation, and survival (review by Lu and Zhou, 2007).CLONING
Maleszka et al. (1996) sequenced the region of DNA adjacent to the Drosophila flightless (fli) gene, which is homologous to human FLII (600362). They characterized 4 transcriptional units within this region of the Drosophila genome, including the dod gene. By database analysis, Maleszka et al. (1996) identified human DOD, or PIN1, which encodes a predicted 163-amino acid protein. Both Drosophila and human DOD contain a WW domain for protein-protein interactions and a peptidylprolyl cis-trans isomerase (PPIase; EC 5.2.1.8) domain, and they are related to the Ess1 cell division gene of Saccharomyces cerevisiae. Lu et al. (1996) also described human PIN1.GENE FUNCTION
Maleszka et al. (1996) found that expression of the Drosophila dod gene product in S. cerevisiae rescued the lethal phenotype of Ess1 mutation. Lu et al. (1996) showed that deletion of PIN1 from HeLa cells induced mitotic arrest, whereas HeLa cells overexpressing PIN1 arrested in G2 phase. In the frog, Pin1 is implicated in the regulation of cell cycle progression and required for the DNA replication checkpoint. By fluorescence microscopy, Winkler et al. (2000) observed that nuclear extracts from Xenopus eggs depleted of Pin1 inappropriately transited from the G2 to the M phase of the cell cycle in the presence of a DNA replication inhibitor. Immunoblot analysis revealed that inappropriate transition was accompanied by hyperphosphorylation of CDC25 (see CDC25A, 116947), activation of CDC2 (116940)/cyclin B (123836), and mitotic phosphoproteins. Addition of recombinant wildtype, but not mutant, Pin1 reversed the defect in replication checkpoint function. Liou et al. (2002) demonstrated that loss of Pin1 function in mouse causes phenotypes resembling cyclin D1 (168461)-null phenotypes. Their findings confirmed that Pin1 positively regulates cyclin D1 function at the transcriptional level and also through posttranslational stabilization. The results provided genetic evidence for an essential role of Pin1 in maintaining cell proliferation and regulating cyclin D1 function. Zacchi et al. (2002) demonstrated that, on DNA damage, p53 (191170) interacts with PIN1, which regulates the function of many proteins involved in cell cycle control and apoptosis. The interaction is strictly dependent on p53 phosphorylation, and requires ser33, thr81, and ser315. On binding, PIN1 generates conformational changes in p53, enhancing its transactivation activity. Stabilization of p53 is impaired in UV-treated Pin1 -/- cells owing to its inability to efficiently dissociate from MDM2 (164785). As a consequence, a reduced p53-dependent response was detected in Pin1 -/- cells, and this correlated with a diminished transcriptional activation of some p53-regulated genes. Zacchi et al. (2002) concluded that following stress-induced phosphorylation, p53 needs to form a complex ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601052 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed