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Information on EC 5.2.1.8 - peptidylprolyl isomerase and Organism(s) Mus musculus and UniProt Accession Q61576
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5.2.1.8 peptidylprolyl isomeraseIUBMB Comments
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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- 5.2.1.8
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cyclosporine
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isomerization
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voltage-dependent
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phosphorylation-dependent
- ns5a
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ca2+-induced
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direct-acting
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normfinder
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ribosome-associated
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The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
cyclophilin, cyclophilin a, fkbp12, ppiase, fkbp51, trigger factor, fkbp52, fk506-binding protein, peptidyl-prolyl isomerase, cyclophilin b, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
12 kDa FKBP
-
-
-
-
12.6 kDa FKBP
-
-
-
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13 kDa FKBP
-
-
-
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15 kDa FKBP
-
-
-
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19 kDa FK506-binding protein
-
-
-
-
22 kDa FK506-binding protein
-
-
-
-
25 kDa FKBP
-
-
-
-
27 kDa membrane protein
-
-
-
-
36 kDa FK506 binding protein
-
-
-
-
40 kDa thylakoid lumen PPIase
-
-
-
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40 kDa thylakoid lumen rotamase
-
-
-
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51 kDa FK506-binding protein
-
-
-
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52 kDa FK506 binding protein
-
-
-
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54 kDa progesterone receptor-associated immunophilin
-
-
-
-
65 kDa FK506-binding protein
-
-
-
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CGI-124
-
-
-
-
Chl-Mip
-
-
-
-
CPH
-
-
-
-
Cyclophilin
-
-
-
-
Cyclophilin 18
-
-
-
-
Cyclophilin 33
-
-
-
-
Cyclophilin A
-
-
-
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Cyclophilin B
-
-
-
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Cyclophilin C
-
-
-
-
Cyclophilin cyp2
-
-
-
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Cyclophilin homolog
-
-
-
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Cyclophilin ScCypA
-
-
-
-
Cyclophilin ScCypB
-
-
-
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Cyclophilin-10
-
-
-
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Cyclophilin-11
-
-
-
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Cyclophilin-40
-
-
-
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Cyclophilin-60
-
-
-
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Cyclophilin-like protein Cyp-60
-
-
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Cyclophilin-related protein
-
-
-
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Cyclosporin A-binding protein
-
-
-
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CYP-40
-
-
-
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CYP-S1
-
-
-
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Cyp3 PPIase
-
-
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CyPA
-
-
-
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CyPB
-
-
-
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Estrogen receptor binding cyclophilin
-
-
-
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FF1 antigen
-
-
-
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FKBP
-
-
-
-
FKBP-12
-
-
-
-
FKBP-12.6
-
-
-
-
FKBP-13
-
-
-
-
FKBP-15
-
-
-
-
FKBP-19
-
-
-
-
FKBP-21
-
-
-
-
FKBP-22
-
-
-
-
FKBP-23
-
-
-
-
FKBP-25
-
-
-
-
FKBP-36
-
-
-
-
FKBP-51
-
-
-
-
FKBP-70
-
-
-
-
FKBP22
-
-
-
-
FKBP52 protein
-
-
-
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FKBP54
-
-
-
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FKBP59
-
-
-
-
FKBP65
-
-
-
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FKBP65RS
-
-
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HBI
-
-
-
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Histidine rich protein
-
-
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hPar14
-
-
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HSP binding immunophilin
-
-
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HSP90-binding immunophilin
-
-
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Immunophilin FKBP12
-
-
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Immunophilin FKBP12.6
-
-
-
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Immunophilin FKBP36
-
-
-
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Immunophilin FKBP65
-
-
-
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Isomerase, peptidylprolyl cis-trans
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-
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Macrolide binding protein
-
-
-
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Macrophage infectivity potentiator
-
-
-
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MtFK
-
-
-
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Nucleolar proline isomerase
-
-
-
-
p17.7
-
-
-
-
P31
-
-
-
-
P54
-
-
-
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p59 protein
-
-
-
-
Par14
Parvulin
Parvulin 14
-
-
-
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Peptide bond isomerase
-
-
-
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Peptidyl-prolyl cis-trans isomerase
Peptidyl-prolyl cis-trans isomerase plp
-
-
-
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Peptidyl-prolyl cis-trans isomerase surA
-
-
-
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Peptidyl-prolyl cis/trans isomerase EPVH
-
-
-
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Peptidylprolyl cis-trans isomerase
-
-
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PfCyP
-
-
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Pin1
Planta-induced rust protein 28
-
-
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PPIase
PPIase Pin1
-
-
-
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PPIase Pin4
-
-
-
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Proline rotamase
-
-
-
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Proteins, cyclophilins
-
-
-
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Proteins, specific or class, cyclophilins
-
-
-
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Rapamycin-binding protein
-
-
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Rapamycin-selective 25 kDa immunophilin
-
-
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Rotamase
-
-
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Rotamase Pin1
-
-
-
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Rotamase Pin4
-
-
-
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Rotamase plp
-
-
-
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S-cyclophilin
-
-
-
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S1205-06
-
-
-
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SCYLP
-
-
-
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SmCYP A
-
-
-
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SmCYP B
-
-
-
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Smp17.7
-
-
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SP18
-
-
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WHP
-
-
-
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Par14
-
-
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Parvulin
-
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Peptidyl-prolyl cis-trans isomerase
-
-
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PPIase
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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.
CAS REGISTRY NUMBER
COMMENTARY
95076-93-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(cis)-Pro in microtubule associated protein tau
(trans)-Pro in microtubule associated protein tau
-
-
-
?
(cis)-Pro residue in protein FOXO3
(trans)-Pro residue in protein FOXO3
-
-
-
r
acetyl-Ala-Ala-Ser(PO3H2)-(cis)-Pro-Arg-NH-4-nitroanilide
acetyl-Ala-Ala-Ser(PO3H2)-(trans)-Pro-Arg-NH-4-nitroanilide
-
-
-
-
?
succinyl-Ala-Glu-(trans)-Pro-Phe-7-amido-4-methylcoumarin
succinyl-Ala-Glu-(cis)-Pro-Phe-7-amido-4-methylcoumarin
-
-
-
r
additional information
?
-
-
the enzyme is involved in cell cycle progression
-
?
additional information
?
-
-
general function of enzyme in binding of cargo for retrograde movement along microtubules
-
-
?
additional information
?
-
-
Par14 behaves as a component of the preribosomal ribonucleoprotein, pre-rRNP, complexes in vivo interacting via its residues 36-41, proteomics analysis of the Par14-associated pre-rRNP complexes, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
the enzyme is involved in cell cycle progression
-
?
additional information
?
-
-
general function of enzyme in binding of cargo for retrograde movement along microtubules
-
-
?
additional information
?
-
-
Par14 behaves as a component of the preribosomal ribonucleoprotein, pre-rRNP, complexes in vivo interacting via its residues 36-41, proteomics analysis of the Par14-associated pre-rRNP complexes, overview
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,7-dimethylbenzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetrone
-
IC50: 0.002 mM
diethyl 1,3,8,10-tetrahydro-1,3,8,10-tetraoxoanthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-2,9-diacetate
-
IC50: 0.0015 mM
diethyl-1,3,6,8-tetrahydro-1,3,6,8-tetraoxobenzo[lmn][3,8]phenanthroline 2,7-diacetate
-
IC50: 0.0015 mM, inhibitor with the least non-specific toxicity
additional information
-
Pin1 inhibitors may be used as a novel type of anticancer drug that acts by blocking cell cycle progression
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
equine chorionic gonadotropin
significant increase in expression of isoform Pin1 mRNA, application of human chorionic gonadotropin attenuates this increase. mRNA expression of E2F transcription factor, which controls the expression of Pin1, is decreased in the ovaries after treatment with equine chorionic gonadotropin. Protein level of Pin1 shows the same tendencies as the expression of RNA
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
2,7-dimethylbenzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetrone
Mus musculus
-
IC50: 0.002 mM
0.0015
diethyl 1,3,8,10-tetrahydro-1,3,8,10-tetraoxoanthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-2,9-diacetate
Mus musculus
-
IC50: 0.0015 mM
0.0015
diethyl-1,3,6,8-tetrahydro-1,3,6,8-tetraoxobenzo[lmn][3,8]phenanthroline 2,7-diacetate
Mus musculus
-
IC50: 0.0015 mM, inhibitor with the least non-specific toxicity
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
comparative analysis of enzyme activities and mRNA level of Pin1 and other prolyl cis/trans isomerases
-
comparative analysis of enzyme activities and mRNA level of Pin1 and other prolyl cis/trans isomerases
of mice treated with equine or human chorionic gonadotropin, eCG or hCG, resp.
-
comparative analysis of enzyme activities and mRNA level of Pin1 and other prolyl cis/trans isomerases
-
embryonic fibroblast,comparative analysis of enzyme activities and mRNA level of Pin1 and other prolyl cis/trans isomerases
-
comparative analysis of enzyme activities and mRNA level of Pin1 and other prolyl cis/trans isomerases
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
endogenous Par14 is present in nuclear Pre-40 S and Pre-60 S ribosomal fractions
additional information
-
co-localizing with the nucleolar-specific protein B23 in quiescent cells, Par14 localizes to the nucleolus of those cells during interphase, and Par14 co-localized almost completely with B23 in the spindle apparatus during mitosis
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
enzyme regulates lysyl hydroxylase LH2-mediated collagen cross-linking. FKBP65 deficiency diminishes hydroxylysine-aldehyde derived intermolecular collagen cross-links and increases the non-hydroxylated lysine-aldehyde-derived collagen cross-links
malfunction
-
Pin1 knock-out mice exhibit impaired insulin signaling with glucose intolerance. Pin1 knock-out mice are resistant to diet-induced obesity
physiological function
physiological function
-
peptidyl-prolyl isomerase, Pin1, is a critical regulator of NF-kappaB activation facilitating NF-kappaB binding in hepatocytes and protects against hepatic ischemia/reperfusion injury. Pin1 is required for full production of MIP-2, but not for production of TNFalpha
physiological function
-
Pin1 plays a critical role in adipose differentiation. Pin1 binds to IRS-1 and thereby markedly enhances insulin action, essential for adipogenesis
physiological function
In response to genotoxic drug doxorubicin, Pin1 binds and decreases levels of the phosphorylated Foxo3, the positive transcription factor of P-glycoprotein (P-gp) gene. Thereby, Pin1 decreases the level of P-gp and signals the cell to pump the genotoxic drugs out
physiological function
mice lacking the Pin1 gene form more megakaryocytes than wild type mice, and the proplatelet formation of megakaryocytes is poorer in Pin1-/- mice than in wild-type mice. Treatment of megakaryoblastic floating cell line Meg-01 with shRNA against Pin1 suppresses the proplatelet formation. Expression of tau, a microtubule associated protein is induced in megakaryocytes during proplatelet formation. Pin1 binds tau and promotes microtubule polymerization
physiological function
PIN1 inhibition dramatically reduces the tumor volume in a subcutaneous mouse xenograft model and angiogenesis as well as hypoxia-induced transcriptional activity of hypoxia-inducible factor HIF-1alpha
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). FKB10_MOUSE
581
0
64697
Swiss-Prot
Mitochondrion (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of murine cyclophilin C complexed with immunosuppressive drug cyclosporin A
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R68/69A
mutant has lost the binding site to the phosphorylated Ser/Thre-Pro residues of substrates, still is able to decrease the transcriptional activity of FOXO3
W34A
mutant lacks the WW motif of the FOXO3 binding site, is not able to decrease the transcriptional activity of FOXO3
additional information
-
Pin1 knockout mice show reduced neutrophile accumulation in the liver, reduced NF-kappaB activation, and increased nuclear p65 protein expression compared to wild-type mice, phenotypes, overview
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the overexpression of Pin1 in Hep-G2 cells markedly enhances insulin-induced IRS-1 phosphorylation and its downstream events: phosphatidylinositol 3-kinase binding with IRS-1andAkt phosphorylation. Pin1 expression is up-regulated in accordance with nutrient conditions such as food intake or a high-fat diet
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
Pin1 inhibitors can be used as a novel type of anticancer drug that acts by blocking cell cycle progression
medicine
PIN1 inhibition dramatically reduces the tumor volume in a subcutaneous mouse xenograft model and angiogenesis as well as hypoxia-induced transcriptional activity of hypoxia-inducible factor HIF-1alpha
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ke, H.; Zhao, Y.; Luo, F.; Weissman, I.; Friedman, J.
Crystal structure of murine cyclophilin C complexed with immunosuppressive drug cyclosporin A
Proc. Natl. Acad. Sci. USA
90
11850-11854
1993
Mus musculus
Uchida, T.; Takamiya, M.; Takahashi, M.; Miyashita, H.; Ikeda, H.; Terada, T.; Matsuo, Y.; Shirouzu, M.; Yokoyama, S.; Fujimori, F.; Hunter, T.
Pin1 and Par14 peptidyl prolyl isomerase inhibitors block cell proliferation
Chem. Biol.
10
15-24
2003
Mus musculus
Galigniana, M.D.; Morishima, Y.; Gallay, P.A.; Pratt, W.B.
Cyclophilin-A is bound through its peptidylprolyl isomerase domain to the cytoplasmic dynein motor protein complex
J. Biol. Chem.
279
55754-55759
2004
Oryctolagus cuniculus, Mus musculus
Fanghaenel, J.; Akiyama, H.; Uchida, C.; Uchida, T.
Comparative analysis of enzyme activities and mRNA levels of peptidyl prolyl cis/trans isomerases in various organs of wild type and Pin1-/- mice
FEBS Lett.
580
3237-3245
2006
Mus musculus
Shimizu, T.; Akiyama, H.; Abe, Y.; Sasada, H.; Sato, E.; Miyamoto, A.; Uchida, T.
Expression of Pin1, a peptidyl-prolyl isomerase, in the ovaries of eCG/hCG-treated immature female mice
J. Reprod. Dev.
52
287-291
2006
Mus musculus (Q9QUR7)
Kuboki, S.; Sakai, N.; Clarke, C.; Schuster, R.; Blanchard, J.; Edwards, M.J.; Lentsch, A.B.
The peptidyl-prolyl isomerase, Pin1, facilitates NF-kappaB binding in hepatocytes and protects against hepatic ischemia/reperfusion injury
J. Hepatol.
51
296-306
2009
Mus musculus
Fujiyama-Nakamura, S.; Yoshikawa, H.; Homma, K.; Hayano, T.; Tsujimura-Takahashi, T.; Izumikawa, K.; Ishikawa, H.; Miyazawa, N.; Yanagida, M.; Miura, Y.; Shinkawa, T.; Yamauchi, Y.; Isobe, T.; Takahashi, N.
Parvulin (Par14), a peptidyl-prolyl cis-trans isomerase, is a novel rRNA processing factor that evolved in the metazoan lineage
Mol. Cell. Proteomics
8
1552-1565
2009
Homo sapiens, Mus musculus
Nakatsu, Y.; Sakoda, H.; Kushiyama, A.; Zhang, J.; Ono, H.; Fujishiro, M.; Kikuchi, T.; Fukushima, T.; Yoneda, M.; Ohno, H.; Horike, N.; Kanna, M.; Tsuchiya, Y.; Kamata, H.; Nishimura, F.; Isobe, T.; Ogihara, T.; Katagiri, H.; Oka, Y.; Takahashi, S.; Kurihara, H.; Uchida, T.; Asano, T.
Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with insulin receptor substrate-1 and enhances insulin actions and adipogenesis
J. Biol. Chem.
286
20812-20822
2011
Homo sapiens, Mus musculus
Chen, Y.; Terajima, M.; Banerjee, P.; Guo, H.; Liu, X.; Yu, J.; Yamauchi, M.; Kurie, J.M.
FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch
Sci. Rep.
7
46021
2017
Mus musculus (Q61576), Mus musculus
Shimizu, T.; Bamba, Y.; Kawabe, Y.; Fukuda, T.; Fujimori, F.; Takahashi, K.; Uchida, C.; Uchida, T.
Prolyl isomerase Pin1 regulates doxorubicin-inducible P-glycoprotein level by reducing Foxo3 stability
Biochem. Biophys. Res. Commun.
471
328-333
2016
Mus musculus (Q9QUR7)
Shimizu, T.; Uchida, C.; Shimizu, R.; Motohashi, H.; Uchida, T.
Prolyl isomerase Pin1 promotes proplatelet formation of megakaryocytes via tau
Biochem. Biophys. Res. Commun.
493
946-951
2017
Mus musculus (Q9QUR7)
Han, H.J.; Kwon, N.; Choi, M.A.; Jung, K.O.; Piao, J.Y.; Ngo, H.K.; Kim, S.J.; Kim, D.H.; Chung, J.K.; Cha, Y.N.; Youn, H.; Choi, B.Y.; Min, S.H.; Surh, Y.J.
Peptidyl prolyl isomerase PIN1 directly binds to and stabilizes hypoxia-inducible factor-1alpha
PLoS ONE
11
e0147038
2016
Homo sapiens (Q13526), Mus musculus (Q9QUR7)
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