Genome location: Pf3D7_12_v3:1,954,020..1,957,694(-)
Genome classification: Core
Product Description: peptidyl-prolyl cis-trans isomerase FKBP35
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 5.2.1.8 (Peptidylprolyl isomerase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005634 | nucleus |
| Function | GO:0005528 | FK506 binding |
| Function | GO:0003755 | peptidyl-prolyl cis-trans isomerase activity |
| Function | GO:0046983 | protein dimerization activity |
| Process | GO:0061077 | chaperone-mediated protein folding |
| Process | GO:0032515 | negative regulation of phosphoprotein phosphatase activity |
| Process | GO:0006457 | protein folding |
| Process | GO:0000413 | protein peptidyl-prolyl isomerization |
| Process | GO:0009410 | response to xenobiotic stimulus |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | expressed | N/A | N/A |
| Ring | expressed | 0.35 | 0.84 |
| Trophozoite | expressed | 1.15 | 0.45 |
| Schizont | expressed | 0.22 | 0.85 |
| Gametocyte | expressed | 0.59 | 0.68 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1247400
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.126 | MFS: -2.83 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PY17X_1463000)
Modification: Tagged | RMgm-1565
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I4V8
"Best" AlphaFill ligand hit: DTV ((2s,3s)-1,4-dimercaptobutane-2,3-diol, Local RMSD=0.12) with 4QT3 (Global RMSD=1.33)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 5.2.1.8 | peptidylprolyl isomerase | ATPNEMSDSPCMBFK506QAEGPKAla-ProjugloneSer-ProGPI-1046RNase T1Rapamycin... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P18203 | Peptidyl-prolyl cis-trans isomerase FKBP1A | Bos taurus | OrthoDB | N-Glyoxylprolyl ketone, 5aN-Glyoxylprolyl ketone, 5bN-Glyoxylprolyl ketone, 5cN-Glyoxylprolyl ketone, 5e... |
| Q00688 | Peptidyl-prolyl cis-trans isomerase FKBP3 | Homo sapiens | OrthoDB | CHEMBL4090599 |
| Q13451 | Peptidyl-prolyl cis-trans isomerase FKBP5 | Homo sapiens | OrthoDB, OrthoMCL BLAST | CHEMBL3623623CHEMBL3623622CHEMBL3623621CHEMBL3623620... |
| P62942 | Peptidyl-prolyl cis-trans isomerase FKBP1A | Homo sapiens | OrthoDB | Tetracyclic aza-amide, 5aTetracyclic aza-amide, 5bTetracyclic aza-amide, 5cTetracyclic aza-amide, 5d... |
| Q02790 | Peptidyl-prolyl cis-trans isomerase FKBP4 | Homo sapiens | OrthoDB | CHEMBL3623618Cyclosporine AASCOMYCINCHEMBL4090599... |
| Q8QGU2 | Peptidylprolyl isomerase | Gallus gallus | OrthoDB, OrthoMCL | CHEMBL51710CHEMBL417192CHEMBL54189CHEMBL300040... |
| P68106 | Peptidyl-prolyl cis-trans isomerase FKBP1B | Homo sapiens | OrthoDB | CHEMBL2370706CHEMBL2370707CHEMBL216520CHEMBL2370711... |
Ortholog Group (OrthoMCL): OG6_100299
Most Similar Human Ortholog: F5H1U3
TM-align score: 0.98 | RMSD: 0.50
Seq Identity: 0.45 | Length: 86 / 304
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000004478 | FKBP prolyl isomerase 4 |
| ENSG00000096060 | FKBP prolyl isomerase 5 |
| ENSG00000119782 | FKBP prolyl isomerase 1B |
| ENSG00000198225 | FKBP prolyl isomerase 1C |
Protein Length: 304 | Molecular Weight (kDa): 34.827
UniProt ID(s): Q8I4V8
PDB ID(s): 2FBN, 2OFN, 2VN1, 4J4N, 4QT2, 4QT3
Isoelectric Point: 5.13
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001179 | FKBP-type peptidyl-prolyl cis-trans isomerase domain |
| InterPro | IPR011990 | Tetratricopeptide-like helical domain superfamily |
| InterPro | IPR019734 | Tetratricopeptide repeat |
| PFam | PF00254 | FKBP-type peptidyl-prolyl cis-trans isomerase domain |
| PFam | PF13181 | Tetratricopeptide repeat |
| Superfamily | SSF48452 | Tetratricopeptide-like helical domain superfamily |
| Superfamily | SSF54534 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 0 | 0 | 0 | 0 |
| disruptive | 0 | 0 | 0 | 1 |
| missense | 0 | 0 | 0 | 0 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 0 | 0 | 0 | 0 |
| disruptive | 0 | 0 | 1 | 0 |
| missense | 0 | 0 | 0 | 0 |
PlasmoDB Total SNPs: 170
Non-coding: 157 | Synonymous: 12 | Nonsynonymous: 1 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 15664653 | A Plasmodium falciparum FK506-binding protein (FKBP) with peptidyl-prolylcis-trans isomerase and chaperone activities. | Monaghan P, Bell A | 10.1016/j.molbiopara.2004.10.007 |
| 15850699 | The FK506-binding protein of the malaria parasite, Plasmodium falciparum, is aFK506-sensitive chaperone with FK506-independent calcineurin-inhibitory activity. | Kumar R, Adams B, ..., Barik S | 10.1016/j.molbiopara.2005.02.007 |
| 17289400 | Expression, purification, and molecular characterization of Plasmodium falciparumFK506-binding protein 35 (PfFKBP35). | Yoon HR, Kang CB, ..., Yoon HS | 10.1016/j.pep.2006.12.019 |
| 23181666 | Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. | Oehring SC, Woodcroft BJ, ..., Voss TS | 10.1186/gb-2012-13-11-r108 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 33209191 | Targeted Covalent Inhibition of Plasmodium FK506 Binding Protein 35. | Atack TC, Raymond DD, ..., Sellers WR | https://pubmed.ncbi.nlm.nih.gov/33209191/ |
| 37934560 | Genetic validation of PfFKBP35 as an antimalarial drug target | Thommen BT, Dziekan JM, ..., Brancucci NMB | 10.7554/eLife.86975 |
| 31120120 | Expression and characterization of functional domains of FK506-binding protein 35 from Plasmodium knowlesi | Goh CKW, Silvester J, ..., Budiman C | 10.1093/protein/gzz008 |
| 23974147 | Small molecule Plasmodium FKBP35 inhibitor as a potential antimalaria agent | Harikishore A, Niang M, ..., Yoon HS | 10.1038/srep02501 |
| 18465874 | Crystal structure of the FK506 binding domain of Plasmodium falciparum FKBP35 incomplex with FK506 | Kotaka M, Ye H, ..., Lescar J | 10.1021/bi800004u |
| 36118020 | Structural insights into Plasmodium PPIases | Rajan S, Yoon HS | 10.3389/fcimb.2022.931635 |
| 19636818 | 1H, 13C, and 15N resonance assignments of FK506-binding domain of Plasmodiumfalciparum FKBP35 | Kang CB, Ye H, Yoon HR, Yoon HS | 10.1007/s12104-007-9005-4 |
| 32035313 | Understanding the potency of malarial ligand (D44) in plasmodium FKBP35 andmodelled halogen atom (Br, Cl, F) functional groups | Deepa P, Thirumeignanam D | 10.1016/j.jmgm.2020.107553 |
| 26057671 | Two crystal structures of the FK506-binding domain of Plasmodium falciparumFKBP35 in complex with rapamycin at high resolution | Bianchin A, Allemand F, ..., Guichou JF | 10.1107/S1399004715006239 |
| 25978804 | Molecular docking study of macrocycles as Fk506-binding protein inhibitors | MacDonald CA, Boyd RJ | 10.1016/j.jmgm.2015.04.009 |
| 19691130 | Crystallographic structure of the tetratricopeptide repeat domain of Plasmodiumfalciparum FKBP35 and its molecular interaction with Hsp90 C-terminalpentapeptide | Alag R, Bharatham N, ..., Yoon HS | 10.1002/pro.226 |
| 24900611 | Adamantyl derivative as a potent inhibitor of Plasmodium FK506 binding protein35 | Harikishore A, Leow ML, ..., Yoon HS | 10.1021/ml400306r |
| 20572013 | NMR and crystallographic structures of the FK506 binding domain of human malarialparasite Plasmodium vivax FKBP35 | Alag R, Qureshi IA, ..., Yoon HS | 10.1002/pro.438 |
| 26091727 | Computational insights into the suicide inhibition of Plasmodium falciparumFk506-binding protein 35 | MacDonald CA, Boyd RJ | 10.1016/j.bmcl.2015.05.079 |