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FKBP prolyl isomerase 1A

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Target id: 2609

Nomenclature: FKBP prolyl isomerase 1A

Abbreviated Name: FKBP12

Family: Peptidyl-prolyl cis/trans isomerases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 108 20p13 FKBP1A FKBP prolyl isomerase 1A
Mouse - 108 2 G3 Fkbp1a FK506 binding protein 1a
Rat - 108 3q41 Fkbp1a FKBP prolyl isomerase 1A
Previous and Unofficial Names Click here for help
FK506 binding protein 1a | FK506 binding protein 1A | FK506 binding protein 1A, 12kDa | FKBP12 | Peptidyl-prolyl cis-trans isomerase FKBP1A | PKC12 | PPIASE
Database Links Click here for help
Alphafold P62942 (Hs), P26883 (Mm), Q62658 (Rn)
BRENDA 5.2.1.8
ChEMBL Target CHEMBL1902 (Hs), CHEMBL4295736 (Mm), CHEMBL2095 (Rn)
DrugBank Target P62942 (Hs)
Ensembl Gene ENSG00000088832 (Hs), ENSMUSG00000032966 (Mm), ENSRNOG00000008822 (Rn)
Entrez Gene 2280 (Hs), 14225 (Mm), 25639 (Rn)
Human Protein Atlas ENSG00000088832 (Hs)
KEGG Enzyme 5.2.1.8
KEGG Gene hsa:2280 (Hs), mmu:14225 (Mm), rno:25639 (Rn)
OMIM 186945 (Hs)
Pharos P62942 (Hs)
RefSeq Nucleotide NM_000801 (Hs), NM_008019 (Mm), NM_013102 (Rn)
RefSeq Protein NP_000792 (Hs), NP_032045 (Mm), NP_037234 (Rn)
SynPHARM 80549 (in complex with sirolimus)
78882 (in complex with tacrolimus)
UniProtKB P62942 (Hs), P26883 (Mm), Q62658 (Rn)
Wikipedia FKBP1A (Hs)
Enzyme Reaction Click here for help
EC Number: 5.2.1.8

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
sirolimus Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.7 pKi 4
⤷ pKi 9.7 (Ki 2x10-10 M) [4]
Description: Measuring ability to inhibit the proteins rotamase activity
tacrolimus Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.4 pKi 4
⤷ pKi 9.4 (Ki 4x10-10 M) [4]
zotarolimus Small molecule or natural product Primary target of this compound Hs Binding 8.6 pIC50 2
⤷ pIC50 8.6 (IC50 2.8x10-9 M) [2]
pimecrolimus Small molecule or natural product Approved drug Primary target of this compound Rn Inhibition 8.2 pIC50 5
⤷ pIC50 8.2 (IC50 6x10-9 M) [5]
Description: Indirect measurement of primary target inhibition via rotamase inhibition
SLF Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - 6.9 pIC50 3
⤷ pIC50 6.9 (IC50 1.14x10-7 M) [3]
Description: Binding affinity determined by a fluorescence polarization assay
cycloheximide Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.5 pIC50 1
⤷ pIC50 5.5 (IC50 3.4x10-6 M) [1]
View species-specific inhibitor tables
Inhibitor Comments
Further information regarding the mechanism of action and clinical use of pimecrolimus is available in these references:- [6-7].
Immuno Process Associations
Immuno Process:  T cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Immuno Process:  Cytokine production & signalling

References

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1. Christner C, Wyrwa R, Marsch S, Küllertz G, Thiericke R, Grabley S, Schumann D, Fischer G. (1999) Synthesis and cytotoxic evaluation of cycloheximide derivatives as potential inhibitors of FKBP12 with neuroregenerative properties. J Med Chem, 42 (18): 3615-22. [PMID:10479292]

2. Garcia-Touchard A, Burke SE, Toner JL, Cromack K, Schwartz RS. (2006) Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks. Eur Heart J, 27 (8): 988-93. [PMID:16449248]

3. Gopalakrishnan R, Kozany C, Wang Y, Schneider S, Hoogeland B, Bracher A, Hausch F. (2012) Exploration of pipecolate sulfonamides as binders of the FK506-binding proteins 51 and 52. J Med Chem, 55 (9): 4123-31. [PMID:22455398]

4. Hamilton GS, Steiner JP. (1998) Immunophilins: beyond immunosuppression. J Med Chem, 41 (26): 5119-43. [PMID:9857082]

5. Hultsch T, Müller KD, Meingassner JG, Grassberger M, Schopf RE, Knop J. (1998) Ascomycin macrolactam derivative SDZ ASM 981 inhibits the release of granule-associated mediators and of newly synthesized cytokines in RBL 2H3 mast cells in an immunophilin-dependent manner. Arch Dermatol Res, 290 (9): 501-7. [PMID:9808344]

6. Luger T, Van Leent EJ, Graeber M, Hedgecock S, Thurston M, Kandra A, Berth-Jones J, Bjerke J, Christophers E, Knop J et al.. (2001) SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis. Br J Dermatol, 144 (4): 788-94. [PMID:11298538]

7. Zuberbier T, Chong SU, Grunow K, Guhl S, Welker P, Grassberger M, Henz BM. (2001) The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) is a potent inhibitor of mediator release from human dermal mast cells and peripheral blood basophils. J Allergy Clin Immunol, 108 (2): 275-80. [PMID:11496246]

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