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Target has curated data in GtoImmuPdb
Target id: 2751
Nomenclature: peptidylprolyl isomerase A
Abbreviated Name: Cyclophilin A
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 165 | 7p13 | PPIA | peptidylprolyl isomerase A | |
Mouse | - | 164 | 11 3.97 cM | Ppia | peptidylprolyl isomerase A | |
Rat | - | 164 | 14q21 | Ppia | peptidylprolyl isomerase A |
Previous and Unofficial Names |
CYPA | peptidylprolyl isomerase A (cyclophilin A) |
Database Links | |
Alphafold | P62937 (Hs), P17742 (Mm), P10111 (Rn) |
BRENDA | 5.2.1.8 |
CATH/Gene3D | 2.40.100.10 |
ChEMBL Target | CHEMBL1949 (Hs), CHEMBL2780 (Rn) |
Ensembl Gene | ENSG00000196262 (Hs), ENSMUSG00000071866 (Mm), ENSRNOG00000027864 (Rn), ENSRNOG00000068764 (Rn) |
Entrez Gene | 5478 (Hs), 268373 (Mm), 25518 (Rn) |
Human Protein Atlas | ENSG00000196262 (Hs) |
KEGG Enzyme | 5.2.1.8 |
KEGG Gene | hsa:5478 (Hs), mmu:268373 (Mm), rno:25518 (Rn) |
OMIM | 123840 (Hs) |
Pharos | P62937 (Hs) |
RefSeq Nucleotide | NM_021130 (Hs), NM_008907 (Mm), NM_017101 (Rn) |
RefSeq Protein | NP_066953 (Hs), NP_032933 (Mm), NP_058797 (Rn) |
SynPHARM | 79182 (in complex with cyclosporin A) |
UniProtKB | P62937 (Hs), P17742 (Mm), P10111 (Rn) |
Wikipedia | PPIA (Hs) |
Selected 3D Structures | |||||||||||||
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Enzyme Reaction | ||||
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Inhibitor Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cyclosporin A does not inhibit calcineurin activity directly. It must be in complex with its immunophilin 'receptor', cyclophilin A (PPIA), before it is able to bind and inhibit calcineurin [8]. |
Immunopharmacology Comments |
Cyclophilin A (CypA) is well known as a specific binding protein for cyclosporin A (CsA) [3]. It is this mechanism that inhibits the calcineurin pathway, an effect that has long been used for immunosuppression in humans [10]. In addition CypA is a molecular chaperone that modulates protein folding by catalyzing cis‐trans isomerization at proline residues (peptidyl‐prolyl cis‐trans isomerase, or PPIase, activity). CypA has intracellular activities, and extracellular functions when it is secreted, either in response to inflammatory activation or as a response to oxidative stress [11]. Extracellular CypA has been proposed as an endogenous ligand for the innate immune triggering receptor expressed on myeloid cells 2 (TREM2: TREM2; Q9NZC2) [4]. In this role CypA influences TREM2 signaling. |
Immuno Process Associations | ||
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1. Bänteli R, Wagner J, Zenke G. (2001) Synthesis of derivatives of the novel cyclophilin-binding immunosuppressant sanglifehrin A with reduced numbers of polar functions. Bioorg Med Chem Lett, 11 (12): 1609-12. [PMID:11412991]
2. Fruman DA, Klee CB, Bierer BE, Burakoff SJ. (1992) Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. Proc Natl Acad Sci USA, 89 (9): 3686-90. [PMID:1373887]
3. Handschumacher RE, Harding MW, Rice J, Drugge RJ, Speicher DW. (1984) Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science, 226 (4674): 544-7. [PMID:6238408]
4. Ji KY, Kim SM, Yee SM, Kim MJ, Ban YJ, Kim EM, Lee EH, Choi HR, Yun H, Lee CW et al.. (2021) Cyclophilin A is an endogenous ligand for the triggering receptor expressed on myeloid cells-2 (TREM2). FASEB J, 35 (4): e21479. [PMID:33710680]
5. Kuglstatter A, Mueller F, Kusznir E, Gsell B, Stihle M, Thoma R, Benz J, Aspeslet L, Freitag D, Hennig M. (2011) Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin). Acta Crystallogr D Biol Crystallogr, 67 (Pt 2): 119-23. [PMID:21245533]
6. Kuo J, Bobardt M, Chatterji U, Mayo PR, Trepanier DJ, Foster RT, Gallay P, Ure DR. (2019) A Pan-Cyclophilin Inhibitor, CRV431, Decreases Fibrosis and Tumor Development in Chronic Liver Disease Models. J Pharmacol Exp Ther, 371 (2): 231-241. [PMID:31406003]
7. Lammers M, Neumann H, Chin JW, James LC. (2010) Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization. Nat Chem Biol, 6 (5): 331-7. [PMID:20364129]
8. Liu J, Farmer Jr JD, Lane WS, Friedman J, Weissman I, Schreiber SL. (1991) Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell, 66 (4): 807-15. [PMID:1715244]
9. Mackman RL, Steadman VA, Dean DK, Jansa P, Poullennec KG, Appleby T, Austin C, Blakemore CA, Cai R, Cannizzaro C et al.. (2018) Discovery of a Potent and Orally Bioavailable Cyclophilin Inhibitor Derived from the Sanglifehrin Macrocycle. J Med Chem, 61 (21): 9473-9499. [PMID:30074795]
10. Porter Jr GA, Beutner G. (2018) Cyclophilin D, Somehow a Master Regulator of Mitochondrial Function. Biomolecules, 8 (4). [PMID:30558250]
11. Yurchenko V, Constant S, Eisenmesser E, Bukrinsky M. (2010) Cyclophilin-CD147 interactions: a new target for anti-inflammatory therapeutics. Clin Exp Immunol, 160 (3): 305-17. [PMID:20345978]