PIN1

PIN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1F8A, 1I6C, 1I8G, 1I8H, 1NMV, 1NMW, 1PIN, 1ZCN, 2F21, 2ITK, 2KBU, 2KCF, 2LB3, 2M8I, 2M8J, 2M9E, 2M9F, 2M9I, 2M9J, 2Q5A, 2RUC, 2RUD, 2XP3, 2XP4, 2XP5, 2XP6, 2XP7, 2XP8, 2XP9, 2XPA, 2XPB, 2ZQS, 2ZQT, 2ZQU, 2ZQV, 2ZR4, 2ZR5, 2ZR6, 3I6C, 3IK8, 3IKD, 3IKG, 3JYJ, 3KAB, 3KAC, 3KAD, 3KAF, 3KAG, 3KAH, 3KAI, 3KCE, 3NTP, 3ODK, 3OOB, 3TC5, 3TCZ, 3TDB, 3WH0, 4GWT, 4GWV, 4QIB, 4TNS, 4TYO, 4U84, 4U85, 4U86, 2RUQ, 2N1O, 2RUR
Identifiers
Aliases	PIN1, DOD, UBL5, peptidylprolyl cis/trans isomerase, NIMA-interacting 1
External IDs	MGI: 1346036 HomoloGene: 4531 GeneCards: PIN1
Gene location (Human) Chr. Chromosome 19 (human)[1] Band No data available Start 9,835,257 bp[1] End 9,849,682 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band No data available Start 20,652,095 bp[2] End 20,666,584 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GTPase activating protein binding • beta-catenin binding • isomerase activity • peptidyl-prolyl cis-trans isomerase activity • protein binding • mitogen-activated protein kinase kinase binding • motor activity • phosphoserine residue binding • phosphothreonine residue binding Cellular component • cytoplasm • cytosol • nuclear speck • midbody • mitochondrion • neuron projection • nucleus • nucleoplasm Biological process • negative regulation of neuron apoptotic process • positive regulation of protein phosphorylation • regulation of cytokinesis • positive regulation of protein dephosphorylation • negative regulation of protein catabolic process • positive regulation of canonical Wnt signaling pathway • synapse organization • negative regulation of cell motility • protein stabilization • negative regulation of transforming growth factor beta receptor signaling pathway • negative regulation of protein binding • protein peptidyl-prolyl isomerization • regulation of protein localization to nucleus • positive regulation of GTPase activity • positive regulation of neuron apoptotic process • positive regulation of ubiquitin-protein transferase activity • neuron differentiation • negative regulation of ERK1 and ERK2 cascade • cell cycle • negative regulation of type I interferon production • positive regulation of cell growth involved in cardiac muscle cell development • regulation of pathway-restricted SMAD protein phosphorylation • positive regulation of transcription from RNA polymerase II promoter • regulation of mitotic nuclear division • regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5300	23988
Ensembl	ENSG00000127445	ENSMUSG00000032171
UniProt	Q13526	Q9QUR7
RefSeq (mRNA)	NM_006221	NM_023371
RefSeq (protein)	NP_006212	NP_075860
Location (UCSC)	Chr 19: 9.84 – 9.85 Mb	Chr 19: 20.65 – 20.67 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 is an enzyme that in humans is encoded by the PIN1 gene.^[5][6] (Not to be confused with PIN1 (Pin-formed 1), an auxin transporter in Arabidopsis thaliana.)

Pin 1, or peptidyl-prolyl cis/trans isomerase (PPIase), isomerizes only phospho-Serine/Threonine-Proline motifs. The enzyme binds to a subset of proteins and thus plays a role as a post phosphorylation control in regulating protein function. Studies have shown that the deregulation of Pin1 may play a pivotal role in various diseases. Notably, the up-regulation of Pin1 is implicated in certain cancers, and the down-regulation of Pin1 is implicated in Alzheimer's disease. Inhibitors of Pin1 may have therapeutic implications for cancer and immune disorders.

Discovery

The gene encoding Pin1 was identified in 1996 as a result of a genetic/biochemical screen for proteins involved in mitotic regulation. It was found to be essential for cell division in some organisms. By 1999, however, it was apparent that Pin1 knockout mice had a surprisingly mild phenotype, indicating that the enzyme was not required for cell division per se. Further studies later found that loss of Pin1 in mice displays are not only neuronal degenerative phenotypes but also several abnormalities, similar to those of cyclin D1-null mice, suggesting the conformation changes mediated by Pin1 may be crucial for cell normal function.

Activation

Phosphorylation of Ser/Thr-Pro motifs in substrates is required for recognition by Pin1. Pin is a small protein at 18 kDa and does not have a nuclear localization or export signal. However, 2009, Lufei et al reported that Pin1 has putative novel nuclear localization signal (NLS) and Pin1 interacts with importin α5 (KPNA1).^[7] Substrate interactions and a WW domain determine subcellular distribution. Expression is induced by growth signals from E2F transcription factors. Expression levels fluctuate in normal, but not in cancerous cells. Expression is often associated with cell proliferation. Postranslational modifications such as phosphorylation on Ser16 inhibit the ability of Pin1 to bind substrate, and this inhibitory process may be altered during oncogenesis. It is hypothesized, but not proven, that Pin1 might also be regulated by proteolytic pathways.

Function

Pin1 activity regulates the outcome of proline-directed kinase (e.g. MAPK, CDK or GSK3) signalling and consequently regulates cell proliferation (in part through control of cyclin D1 levels and stability) and cell survival. The precise effects of Pin1 depend upon the system: Pin1 accelerates dephosphorylation of Cdc25 and Tau, but protects phosphorylated cyclin D from ubiquitination and proteolysis. Recent data also implicate Pin1 as playing an important role in immune responses, at least in part by increasing the stability of cytokine mRNAs by influencing the protein complexes to which they bind. A recent review by Kun Ping Lu attempts to provide a unifying framework for understanding Pin1 function by hypothesising that Pin1 acts as a molecular timer.^[8]

Interactions

PIN1 has been shown to interact with:

References

Further reading