The first type of this enzyme found proved to be the protein cyclophilin, which binds the immunosuppressant cyclosporin A. Other distinct families of the enzyme exist, one being FK-506 binding proteins (FKBP) and another that includes parvulin from Escherichia coli. The three families are structurally unrelated and can be distinguished by being inhibited by cyclosporin A, FK-506 and 5-hydroxy-1,4-naphthoquinone, respectively.
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SYSTEMATIC NAME
IUBMB Comments
Peptidylproline cis-trans-isomerase
The first type of this enzyme found [1] proved to be the protein cyclophilin, which binds the immunosuppressant cyclosporin A. Other distinct families of the enzyme exist, one being FK-506 binding proteins (FKBP) and another that includes parvulin from Escherichia coli. The three families are structurally unrelated and can be distinguished by being inhibited by cyclosporin A, FK-506 and 5-hydroxy-1,4-naphthoquinone, respectively.
Pin1 modulates RNA polymerase II CTD domain during transcription cycles by interacting with numerous YSPTSPS heptapeptide repeats in the substrate protein
FKBP12 and FKBP52 catalyze cis/trans isomerization of regions of TRPC1 implicated in controlling channel opening, molecular mechanism of FKBP52 in TRPC1 channel opening, overview
Pin1 is a peptidyl prolyl cis-trans isomerase that isomerizes phospho-serine/threonine-proline motifs of its target proteins from cis to trans, it functions in concert with proline directed kinases, such as cyclin-dependent protein kinases, extracellular signal-regulated kinases, and c-Jun N-terminal kinase, that produce the phosphorylated substrates of the isomerase, and with protein phosphatases, such as protein phosphatase 1A and 2B, in a wide range of cellular processes including cell division, DNA damage response, and gene transcription, and in susceptibilty to cancer and neurogenerative diseases, regulation, overview
prolyl isomerase Pin1 recognizes and induces cis-trans isomerization of pSer/Thr-Pro bonds, conferring phosphorylation-dependent conformational changes relevant for protein function. Pin1 can directly modulate the NF dephosphorylation mediated by PP2A, independent of JNK, extracellular signal-regulated kinase, and Cdk5 pathways
Pin1 can stimulate proteins phosphorylation, e.g. of the RNA polymerase II CTD domain, but it can also inhibit protein dephosphorylation, e.g. of NFAT transcription factor or calcineurin. Pin1 interacts with neuronal cytoskeleton proteins such as tau, amyloid-beta protein precursor, alpha-synuclein, and with neurofilaments
Pin1 modulates RNA polymerase II CTD domain during transcription cycles by interacting with numerous YSPTSPS heptapeptide repeats in the substrate protein
FKBP12 and FKBP52 catalyze cis/trans isomerization of regions of TRPC1 implicated in controlling channel opening, molecular mechanism of FKBP52 in TRPC1 channel opening, overview
Pin1 is a peptidyl prolyl cis-trans isomerase that isomerizes phospho-serine/threonine-proline motifs of its target proteins from cis to trans, it functions in concert with proline directed kinases, such as cyclin-dependent protein kinases, extracellular signal-regulated kinases, and c-Jun N-terminal kinase, that produce the phosphorylated substrates of the isomerase, and with protein phosphatases, such as protein phosphatase 1A and 2B, in a wide range of cellular processes including cell division, DNA damage response, and gene transcription, and in susceptibilty to cancer and neurogenerative diseases, regulation, overview
prolyl isomerase Pin1 recognizes and induces cis-trans isomerization of pSer/Thr-Pro bonds, conferring phosphorylation-dependent conformational changes relevant for protein function. Pin1 can directly modulate the NF dephosphorylation mediated by PP2A, independent of JNK, extracellular signal-regulated kinase, and Cdk5 pathways
i.e. 5-hydroxy-1,4-naphthalenedione, from leaves, roots, and bark of plants of family Juglandaceae. The compound causes a partial unfolding of the PPIase active site
inhibition of Pin1 inhibits okadaic acid-induced aberrant perikaryal phosphorylation of NF, and inhibition of Pin1 inhibits the okadaic acid- or Fos-induced neuronal apoptosis
FKBP52 mediates stimulus-dependent TRPC1 gating through isomerization, which is required for chemotropic turning of neuronal growth cones to netrin-1 and myelin-associated glycoprotein and for netrin-1/DCC-dependent midline axon guidance of commissural interneurons in the developing spinal cord. By contrast, FKBP12 mediates spontaneous opening of TRPC1 through isomerization and is not required for growth cone responses to netrin-1, PPIase-dependent molecular mechanism, overview. PPIase-dependent regulation of netrin-1-induced Ca2+ influx by FKBP52. FKBP52 and its regulation of TRPC1 are essential for commissural axon guidance in vivo. The PPIase activity of FKBP52 is required for MAG-induced, but not for Sema3-induced, growth cone repulsion
Pin1 is a peptidyl prolyl cis-trans isomerase that isomerizes phospho-serine/threonine-proline motifs of its target proteins, it functions in concert with proline directed kinases, such as cyclin-dependent protein kinases, extracellular signal-regulated kinases, and c-Jun N-terminal kinase, and with protein phosphatases, such as protein phosphatase 1A and 2B, in a wide range of cellular processes including cell division, DNA damage response, and gene transcription, and in susceptibility to cancer and neurogenerative diseases, detailed overview. Pin1 modulates excitotoxic and oxidative stress induced by perkaryal phosphorylation of NF-H. Pin1 mediates the neural-specific apoptosis machinery. Pin1 is involved in regulation of SMRT levels. Pin1 plays a post-phosphorylation role in regulating protein function, mechanisms, overview
Pin1 recognizes and induces cis-trans isomerization of pSer/Thr-Pro bonds, conferring phosphorylation-dependent conformational changes relevant for protein function. In cortical neurons, Pin1 modulates the topographic phosphorylation of the proline-directed Ser/Thr residues within the tail domain of NF proteins by inhibiting the dephosphorylation by PP2A. Inhibition of Pin1 inhibits okadaic acid-induced aberrant perikaryal phosphorylation of NF, and inhibition of Pin1 inhibits the okadaic acid- or Fos-induced neuronal apoptosis, signaling role of PP2A by Pin1, overview
overexpression of wild-type isoform CypB attenuates endoplasmic reticulum stress-induced cell death, whereas overexpression of isomerase activity-defective mutant R62A increases Ca2+ leakage from the endoplasmic reticulum and generation of reactive oxygen species and decreases mitochondrial membrane potential resulting in cell death
in isoform Pin1-deficient neuronal cell cultures, H2O2 stress-induced phosphoprotein Tau dephosphorylation at Thr231 is significantly lower than in wild-type neurons
enzyme overexpression renders isolated mitochondria far more susceptible to the permeability transition induced by Ca2+ and oxidative stress. Overexpressing cells maintain a lower inner-membrane potential of mitochondria than those of normal cells. Effects are abolished by cyclosporin A. Cyclosporin-D overexpression promotes NO-induced necrosis and inhibits staurosporine-induced apoptosis
overexpression of wild-type isoform CypB attenuates endoplasmic reticulum stress-induced cell death, whereas overexpression of isomerase activity-defective mutant R62A increases Ca2+ leakage from the endoplasmic reticulum and generation of reactive oxygen species and decreases mitochondrial membrane potential resulting in cell death. siRNA-mediated inhibition of CypB expression renders cells more vulnerable to endoplasmic reticulum stress. CypB interacts with the endoplasmic reticulum stress-related chaperones, Bip and Grp94
silencing of Pin1 by siRNA, Pin1 siRNA-transfected neurons show the reduction in perikaryal phosphorylation of NF, siRNA inhibits okadaic acid-induced perikaryal phosphorylation of NF-M/H, immunohistochemic analysis, overview
Purification and N-terminal sequencing of peptidyl-prolyl cis-trans-isomerase from rat liver mitochondrial matrix reveals the existence of a distinct mitochondrial cyclophilin
Galas, M.C.; Dourlen, P.; Begard, S.; Ando, K.; Blum, D.; Hamdane, M.; Buee, L.
The peptidylprolyl cis/trans-isomerase Pin1 modulates stress-induced dephosphorylation of Tau in neurons. Implication in a pathological mechanism related to Alzheimer disease