シクロフィリン、サイクロフィリン
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2012/09/27 00:05:34」(JST)
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peptidylprolyl isomerase A (cyclophilin A) |
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Ribbon diagram of cyclophilin A in complex with ciclosporin (yellow). From PDB 1CWA. |
Identifiers |
Symbol |
PPIA |
Entrez |
5478 |
HUGO |
9253 |
OMIM |
123840 |
RefSeq |
NM_203430 |
UniProt |
Q3KQW3 |
Other data |
EC number |
5.2.1.8 |
Locus |
Chr. 7 p13 |
Pro_isomerase |
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x-ray structure of peptidyl-prolyl cis-trans isomerase a, ppia, rv0009, from mycobacterium tuberculosis. |
Identifiers |
Symbol |
Pro_isomerase |
Pfam |
PF00160 |
Pfam clan |
CL0475 |
InterPro |
IPR002130 |
PROSITE |
PDOC00154 |
SCOP |
1cyh |
SUPERFAMILY |
1cyh |
Available protein structures: |
Pfam |
structures |
PDB |
RCSB PDB; PDBe |
PDBsum |
structure summary |
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Cyclophilins are a family of proteins from vertebrates and other organisms that bind to cyclosporine, an immunosuppressant which is usually used to suppress rejection after internal organ transplants [1]. These proteins have peptidyl prolyl isomerase activity, which catalyzes the isomerization of peptide bonds from trans form to cis form at proline residues and facilitates protein folding.
Cyclophilin A is a cytosolic and highly abundant protein. The protein belongs to a family of isozymes, including cyclophilins B and C, and natural killer cell cyclophilin-related protein.[2][3][4] Major isoforms have been found throughout the cell, including the ER, and some are even secreted.
Contents
- 1 Cyclophilin A (CycA)
- 2 Cyclophilin D
- 3 Examples
- 4 References
- 5 External links
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Cyclophilin A (CycA)
Cyclophilin A also known as peptidylprolyl isomerase A, which is found in the cytosol, has a beta barrel structure with two alpha helices and a beta-sheet. Other cyclophilins have similar structures to cyclophilin A. The ciclosporin-cyclophilin A complex inhibits a calcium/calmodulin-dependent phosphatase, calcineurin, the inhibition of which is thought to suppress organ rejection by halting the production of the pro-inflammatory molecules TNF alpha and interleukin 2.
Cyclophilin A is also known to be recruited by the Gag polyprotein during HIV-1 virus infection, and its incorporation into new virus particles is essential for HIV-1 infectivity.
Cyclophilin D
Cyclophilin D, which is located in the matrix of mitochondria, is only a modulatory, but not structural component of the mitochondrial permeability transition pore [5] [6] . The pore opening raises the permeability of the mitochondrial inner membrane, allows influx of cytosolic molecules into the mitochondrial matrix, increases the matrix volume, and disrupts the mitochondrial outer membrane. As a result, the mitochondria fall into a functional disorder, so the opening of the pore plays an important role in cell death. Cyclophilin D is thought to regulate the opening of the pore because cyclosporin A (CsA), which binds to CyP-D, inhibits the pore opening. However, mitochondria obtained from the cysts of Artemia franciscana, do not exhibit the mitochondrial permeability transition pore [7] [8]
Examples
Human genes encoding proteins containing the cyclophilin type peptidyl-prolyl cis-trans isomerase domain include:
- PPIA, PPIB, PPIC, PPID, PPIE, PPIF, PPIG, PPIH
- PPIL1, PPIL2, PPIL3, PPIL4, PPIAL4, PPIL6
- PPWD1
References
- ^ Stamnes MA, Rutherford SL, Zuker CS (September 1992). "Cyclophilins: a new family of proteins involved in intracellular folding". Trends Cell Biol. 2 (9): 272–6. doi:10.1016/0962-8924(92)90200-7. PMID 14731520.
- ^ Trandinh CC, Pao GM, Saier MH (December 1992). "Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl-prolyl cis-trans isomerases". FASEB J. 6 (15): 3410–20. PMID 1464374.
- ^ Galat A (September 1993). "Peptidylproline cis-trans-isomerases: immunophilins". Eur. J. Biochem. 216 (3): 689–707. doi:10.1111/j.1432-1033.1993.tb18189.x. PMID 8404888.
- ^ Hacker J, Fischer G (November 1993). "Immunophilins: structure-function relationship and possible role in microbial pathogenicity". Mol. Microbiol. 10 (3): 445–56. doi:10.1111/j.1365-2958.1993.tb00917.x. PMID 7526121.
- ^ Basso E, Fante L, Fowlkes J, Petronilli V, Forte MA, Bernardi P (May 2005). "Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D". J. Biol. Chem. 280 (19): 18558–61. doi:10.1074/jbc.C500089200. PMID 15792954.
- ^ Doczi J, Turiák L, Vajda S, et al. (February 2011). "Complex contribution of cyclophilin D to Ca2+-induced permeability transition in brain mitochondria, with relation to the bioenergetic state". J. Biol. Chem. 286 (8): 6345–53. doi:10.1074/jbc.M110.196600. PMC 3057831. PMID 21173147. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3057831/.
- ^ Menze MA, Hutchinson K, Laborde SM, Hand SC (July 2005). "Mitochondrial permeability transition in the crustacean Artemia franciscana: absence of a calcium-regulated pore in the face of profound calcium storage". Am. J. Physiol. Regul. Integr. Comp. Physiol. 289 (1): R68–76. doi:10.1152/ajpregu.00844.2004. PMID 15718386.
- ^ Konràd C, Kiss G, Töröcsik B, et al. (March 2011). "A distinct sequence in the adenine nucleotide translocase from Artemia franciscana embryos is associated with insensitivity to bongkrekate and atypical effects of adenine nucleotides on Ca2+ uptake and sequestration". FEBS J. 278 (5): 822–36. doi:10.1111/j.1742-4658.2010.08001.x. PMID 21205213.
External links
- Cyclophilins at the US National Library of Medicine Medical Subject Headings (MeSH)
Isomerases: geometric (EC 5.2)
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5.2.1 |
FKBP: FKBP1A · FKBP1B · FKBP2 · FKBP3 · FKBP5 · FKBP6 · FKBP8 · FKBP9 · FKBP10 · FKBP52 · FKBPL
other: Cyclophilin · Parvulin · Prolyl isomerase
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 2.7.10
- 2.7.11-12
- 3.1
- 4.1
- 5.1
- 6.1-3
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Transmembrane receptors: Immunoglobulin superfamily immune receptors
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Antibody receptor:
Fc receptor |
Epsilon (ε)
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FcεRI · (FcεRII is C-type lectin)
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Gamma (γ)
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FcγRI · FcγRII · FcγRIII · Neonatal
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Alpha (α)/mu (μ)
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FcαRI · Fcα/μR
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Secretory
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Polymeric immunoglobulin receptor
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Antigen receptor |
B cells
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Antigen receptor
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BCR
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Co-receptor
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stimulate: CD21/CD19/CD81
inhibit: CD22
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Accessory molecules
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Ig-α/Ig-β (CD79)
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T cells
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Ligands
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MHC (MHC class I and MHC class II)
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Antigen receptor
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TCR: TRA@ · TRB@ · TRD@ · TRG@
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Co-receptors
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CD8 (with two glycoprotein chains CD8α and CD8β) · CD4
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Accessory molecules
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CD3 · CD3γ · CD3δ · CD3ε · ζ-chain (also called CD3ζ and TCRζ)
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Cytokine receptor |
see cytokine receptors
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Killer-cell IG-like receptors |
KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KIR3DS1
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Leukocyte IG-like receptors |
LILRA1 · LILRA2 · LILRA3 · LILRA4 · LILRA5 · LILRA6 · LILRB1 · LILRB2 · LILRB3 · LILRB4 · LILRB5 · LILRA6 · LILRA5
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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cell/phys/auag/auab/comp, igrc
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UpToDate Contents
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English Journal
- The prolyl-isomerase Pin1 activates the mitochondrial death program of p53.
- Sorrentino G, Mioni M, Giorgi C, Ruggeri N, Pinton P, Moll U, Mantovani F, Del Sal G.Source1] Laboratorio Nazionale CIB, Area Science Park, Padriciano 99, 34149 Trieste, Italy [2] Department of Life Sciences, University of Trieste, 34100 Trieste, Italy.
- Cell death and differentiation.Cell Death Differ.2013 Feb;20(2):198-208. doi: 10.1038/cdd.2012.112. Epub 2012 Aug 31.
- In response to intense stress, the tumor protein p53 (p53) tumor suppressor rapidly mounts a direct mitochondrial death program that precedes transcription-mediated apoptosis. By eliminating severely damaged cells, this pathway contributes to tumor suppression as well as to cancer cell killing induc
- PMID 22935610
- Cyclophilin inhibitors for hepatitis C therapy.
- Membreno FE, Espinales JC, Lawitz EJ.SourceAlamo Medical Research, San Antonio, TX 78215, USA. membreno@alamomedicalresearch.com
- Clinics in liver disease.Clin Liver Dis.2013 Feb;17(1):129-39. doi: 10.1016/j.cld.2012.09.008.
- This article highlights a unique time in the history of hepatitis C therapy. In the last few years new families of direct-acting antivirals have emerged, that block different viral proteins to interrupt viral replication, such as protease, NS5A inhibitors, and NS5B inhibitors. There are few host-tar
- PMID 23177289
- Cyclophilin A predicts clinical outcome in patients with congestive heart failure undergoing endomyocardial biopsy.
- Zuern CS, Müller KA, Seizer P, Geisler T, Banya W, Klingel K, Kandolf R, Bauer A, Gawaz M, May AE.SourceMedizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universitätsklinikum Tübingen, Germany.
- European journal of heart failure.Eur J Heart Fail.2013 Feb;15(2):176-84. doi: 10.1093/eurjhf/hfs185. Epub 2012 Dec 12.
- AIMS: Cyclophilin A (CyPA) represents a ubiquitous intracellular protein, which is secreted by inflammatory and by dying/necrotic cells. The aim of this study was to evaluate the prognostic relevance of CyPA expression in endomyocardial biopsies of consecutive patients with congestive heart failure.
- PMID 23243067
Japanese Journal
- Discovery of Cyclic Peptides Binding to a Cyclophilin Powered by the RaPID System
- ITO Risa,GOTO Yuki,SUGA Hiroaki
- Peptide science : proceedings of the ... Japanese Peptide Symposium 2010, 244, 2011-03-01
- NAID 10028238026
- Cyclophilin A : Promising New Target in Cardiovascular Therapy
- SATOH Kimio,SHIMOKAWA Hiroaki,BERK Bradford C.
- Circulation journal : official journal of the Japanese Circulation Society 74(11), 2249-2256, 2010-10-25
- … Cyclophilin A (CyPA) has been studied as a multifunctional protein that is upregulated in a variety of inflammatory conditions, such as rheumatoid arthritis, autoimmune disease, and cancer. …
- NAID 10026972151
- Identification of cellular and viral factors related to anti-hepatitis C virus activity of cyclophilin inhibitor
- GOTO Kaku,WATASHI Koichi,INOUE Daisuke,HIJIKATA Makoto,SHIMOTOHNO Kunitada
- Cancer science 100(10), 1943-1950, 2009-10-10
- NAID 10027196002
Related Links
- Cyclophilins are a family of proteins from vertebrates and other organisms that bind to cyclosporine, an immunosuppressant which is usually used to suppress rejection after internal organ transplants. These proteins have peptidyl prolyl ...
- Cyclophilin A(CyPA)は,大腸菌からヒトに至る生物. に存在し,細胞質に大量に存在 する蛋白質である 1). ... HIV-1 粒子内に peptidyl-prolyl cis-trans isomerase cyclophilin A(CyPA)が取り込まれることは,. 周知の事実である.しかし,ウイルス 粒子を精製 ...
Related Pictures
★リンクテーブル★
[★]
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-cyclophilin
[★]
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- cyclophilin
- 関
- シクロフィリン