Peptidylprolyl isomerase D

For other uses of the acronym PPID, see PPID.
PPID
Identifiers
Aliases PPID, CYP-40, CYPD, peptidylprolyl isomerase D
External IDs MGI: 1914988 HomoloGene: 31283 GeneCards: PPID
RNA expression pattern


More reference expression data
Orthologs
Species Human Mouse
Entrez

5481

67738

Ensembl

ENSG00000171497

ENSMUSG00000027804

UniProt

Q08752

Q9CR16

RefSeq (mRNA)

NM_005038

NM_026352

RefSeq (protein)

NP_005029.1

NP_080628.1

Location (UCSC) Chr 4: 158.71 – 158.72 Mb Chr 3: 79.59 – 79.6 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Peptidylprolyl isomerase D (cyclophilin D), also known as PPID, is an enzyme which in humans is encoded by the PPID gene on chromosome 4. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the cis-trans isomerization of proline imidic peptide bonds, which allows it to facilitate folding or repair of proteins.[3] In addition, PPID participates in many biological processes, including mitochondrial metabolism, apoptosis, redox, and inflammation, as well as in related diseases and conditions, such as ischemic reperfusion injury, AIDS, and cancer.[4][5][6][7]

Structure

Like other cyclophilins, PPID forms a β-barrel structure with a hydrophobic core. This β-barrel is composed of eight anti-parallel β-strands and capped by two α-helices at the top and bottom. In addition, the β-turns and loops in the strands contribute to the flexibility of the barrel.[6] PPID in particular is composed of 370 residues and shares structural homology with PPIF, FKBP51, and FKBP52, including an N-terminal immunophilin-like domain and a C-terminal tetratricopeptide repeat (TPR) domain.[8]

Function

The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins.[3] Generally, PPIases are found in all eubacteria and eukaryotes, as well as in a few archaebacteria, and thus are highly conserved.[4][9] The PPIase family is further divided into three structurally distinct subfamilies: cyclophilin (CyP), FK506-binding protein (FKBP), and parvulin (Pvn).[4][6] As a cyclophilin, PPID binds cyclosporin A (CsA) and can be found within in the cell or secreted by the cell.[5] In eukaryotes, cyclophilins localize ubiquitously to many cell and tissue types.[5][6] In addition to PPIase and protein chaperone activities, cyclophilins also function in mitochondrial metabolism, apoptosis, immunological response, inflammation, and cell growth and proliferation.[4][5][6] PPID in particular helps chaperone the assembly of heat shock protein Hsp90, as well as the nuclear localization of glucocorticoid, estrogen and progesterone receptors. Along with PPIF, PPID regulates mitochondrial apoptosis. In response to elevated reactive oxygen species (ROS) and calcium ion levels, PPID interacts with Bax to promote mitochondrial pore formation, thus releasing pro-apoptotic factors such as cytochrome C and AIF.[8]

Clinical Significance

As a cyclophilin, PPID binds the immunosuppressive drug CsA to form a CsA-cyclophilin complex, which then targets calcineurin to inhibit the signaling pathway for T-cell activation.

In cardiac myogenic cells, cyclophilins have been observed to be activated by heat shock and hypoxia-reoxygenation as well as complex with heat shock proteins. Thus, cyclophilins may function in cardioprotection during ischemia-reperfusion injury.

Currently, cyclophilin expression is highly correlated with cancer pathogenesis, but the specific mechanisms remain to be elucidated.[5] Studies have shown that PPID protects human keratinocytes from UVA-induced apoptosis, so medication and therapies that inhibit PPID, such as CsA, may inadvertently aid skin cancer development. Conversely, treatments promoting PPID activity may improve patient outcomes when paired with UVA therapies against cancer.[8]

Interactions

PPID has been shown to interact with:

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. 1 2 "Entrez Gene: PPID peptidylprolyl isomerase D (cyclophilin D)".
  4. 1 2 3 4 Kazui T, Inoue N, Yamada O, Komatsu S (Jan 1992). "Selective cerebral perfusion during operation for aneurysms of the aortic arch: a reassessment". The Annals of Thoracic Surgery. 53 (1): 109–14. doi:10.1016/0003-4975(92)90767-x. PMID 1530810.
  5. 1 2 3 4 5 6 Yao Q, Li M, Yang H, Chai H, Fisher W, Chen C (Mar 2005). "Roles of cyclophilins in cancers and other organ systems". World Journal of Surgery. 29 (3): 276–80. doi:10.1007/s00268-004-7812-7. PMID 15706440.
  6. 1 2 3 4 5 Wang T, Yun CH, Gu SY, Chang WR, Liang DC (Aug 2005). "1.88 A crystal structure of the C domain of hCyP33: a novel domain of peptidyl-prolyl cis-trans isomerase". Biochemical and Biophysical Research Communications. 333 (3): 845–9. doi:10.1016/j.bbrc.2005.06.006. PMID 15963461.
  7. ↑ Stocki P, Chapman DC, Beach LA, Williams DB (Aug 2014). "Depletion of cyclophilins B and C leads to dysregulation of endoplasmic reticulum redox homeostasis". The Journal of Biological Chemistry. 289 (33): 23086–96. doi:10.1074/jbc.M114.570911. PMID 24990953.
  8. 1 2 3 4 Jandova J, Janda J, Sligh JE (Mar 2013). "Cyclophilin 40 alters UVA-induced apoptosis and mitochondrial ROS generation in keratinocytes". Experimental Cell Research. 319 (5): 750–60. doi:10.1016/j.yexcr.2012.11.016. PMID 23220213.
  9. ↑ Hoffmann H, Schiene-Fischer C (Jul 2014). "Functional aspects of extracellular cyclophilins". Biological Chemistry. 395 (7-8): 721–35. doi:10.1515/hsz-2014-0125. PMID 24713575.

Further reading

  • Berardini TZ, Bollman K, Sun H, Poethig RS (Mar 2001). "Regulation of vegetative phase change in Arabidopsis thaliana by cyclophilin 40". Science. 291 (5512): 2405–7. doi:10.1126/science.1057144. PMID 11264535. 
  • Kieffer LJ, Thalhammer T, Handschumacher RE (Mar 1992). "Isolation and characterization of a 40-kDa cyclophilin-related protein". The Journal of Biological Chemistry. 267 (8): 5503–7. PMID 1544925. 
  • Hoffmann K, Kakalis LT, Anderson KS, Armitage IM, Handschumacher RE (Apr 1995). "Expression of human cyclophilin-40 and the effect of the His141-->Trp mutation on catalysis and cyclosporin A binding". European Journal of Biochemistry / FEBS. 229 (1): 188–93. doi:10.1111/j.1432-1033.1995.tb20454.x. PMID 7744028. 
  • Kieffer LJ, Seng TW, Li W, Osterman DG, Handschumacher RE, Bayney RM (Jun 1993). "Cyclophilin-40, a protein with homology to the P59 component of the steroid receptor complex. Cloning of the cDNA and further characterization". The Journal of Biological Chemistry. 268 (17): 12303–10. PMID 8509368. 
  • Yokoi H, Shimizu Y, Anazawa H, Lefebvre CA, Korneluk RG, Ikeda JE (Aug 1996). "The structure and complete nucleotide sequence of the human cyclophilin 40 (PPID) gene". Genomics. 35 (3): 448–55. doi:10.1006/geno.1996.0384. PMID 8812478. 
  • Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
  • Silverstein AM, Galigniana MD, Chen MS, Owens-Grillo JK, Chinkers M, Pratt WB (Jun 1997). "Protein phosphatase 5 is a major component of glucocorticoid receptor.hsp90 complexes with properties of an FK506-binding immunophilin". The Journal of Biological Chemistry. 272 (26): 16224–30. doi:10.1074/jbc.272.26.16224. PMID 9195923. 
  • Young JC, Obermann WM, Hartl FU (Jul 1998). "Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa domain of hsp90". The Journal of Biological Chemistry. 273 (29): 18007–10. doi:10.1074/jbc.273.29.18007. PMID 9660753. 
  • Mark PJ, Ward BK, Kumar P, Lahooti H, Minchin RF, Ratajczak T (Jan 2001). "Human cyclophilin 40 is a heat shock protein that exhibits altered intracellular localization following heat shock". Cell Stress & Chaperones. 6 (1): 59–70. doi:10.1379/1466-1268(2001)006<0059:HCIAHS>2.0.CO;2. PMC 434384Freely accessible. PMID 11525244. 
  • Ward BK, Allan RK, Mok D, Temple SE, Taylor P, Dornan J, Mark PJ, Shaw DJ, Kumar P, Walkinshaw MD, Ratajczak T (Oct 2002). "A structure-based mutational analysis of cyclophilin 40 identifies key residues in the core tetratricopeptide repeat domain that mediate binding to Hsp90". The Journal of Biological Chemistry. 277 (43): 40799–809. doi:10.1074/jbc.M207097200. PMID 12145316. 
  • McStay GP, Clarke SJ, Halestrap AP (Oct 2002). "Role of critical thiol groups on the matrix surface of the adenine nucleotide translocase in the mechanism of the mitochondrial permeability transition pore". The Biochemical Journal. 367 (Pt 2): 541–8. doi:10.1042/BJ20011672. PMC 1222909Freely accessible. PMID 12149099. 
  • Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801. 
  • Schubert A, Grimm S (Jan 2004). "Cyclophilin D, a component of the permeability transition-pore, is an apoptosis repressor". Cancer Research. 64 (1): 85–93. doi:10.1158/0008-5472.CAN-03-0476. PMID 14729611. 
  • Machida K, Osada H (Dec 2003). "Molecular interaction between cyclophilin D and adenine nucleotide translocase in cytochrome c release: does it determine whether cytochrome c release is dependent on permeability transition or not?". Annals of the New York Academy of Sciences. 1010: 182–5. doi:10.1196/annals.1299.031. PMID 15033717. 
  • Carrello A, Allan RK, Morgan SL, Owen BA, Mok D, Ward BK, Minchin RF, Toft DO, Ratajczak T (2005). "Interaction of the Hsp90 cochaperone cyclophilin 40 with Hsc70". Cell Stress & Chaperones. 9 (2): 167–81. doi:10.1379/CSC-26R.1. PMC 1065296Freely accessible. PMID 15497503. 
  • Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL (Mar 2005). "High-throughput mapping of a dynamic signaling network in mammalian cells". Science. 307 (5715): 1621–5. doi:10.1126/science.1105776. PMID 15761153. 
  • Machida K, Ohta Y, Osada H (May 2006). "Suppression of apoptosis by cyclophilin D via stabilization of hexokinase II mitochondrial binding in cancer cells". The Journal of Biological Chemistry. 281 (20): 14314–20. doi:10.1074/jbc.M513297200. PMID 16551620. 
  • Mok D, Allan RK, Carrello A, Wangoo K, Walkinshaw MD, Ratajczak T (May 2006). "The chaperone function of cyclophilin 40 maps to a cleft between the prolyl isomerase and tetratricopeptide repeat domains". FEBS Letters. 580 (11): 2761–8. doi:10.1016/j.febslet.2006.04.039. PMID 16650407. 
This article is issued from Wikipedia - version of the 5/20/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.