Genome location: Pf3D7_13_v3:1,724,600..1,727,877(-)
Genome classification: Core
Product Description: kelch protein K13
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: None
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005829 | cytosol |
| Component | GO:0005783 | endoplasmic reticulum |
| Component | GO:0031982 | vesicle |
| Function | GO:0005515 | protein binding |
| Process | GO:0006897 | endocytosis |
| Process | GO:0042493 | response to drug |
| 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 | 1.46 | 0.43 |
| Trophozoite | expressed | 0.42 | 0.76 |
| Schizont | expressed | 0.70 | 0.61 |
| Gametocyte | expressed | 0.45 | 0.75 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1343700
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: 0.122 | MFS: -2.96 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1356700)
Modification: Mutated | RMgm-4878
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IDQ2
"Best" AlphaFill ligand hit: FUM (fumaric acid, Local RMSD=0.32) with 7C5E (Global RMSD=2.24)
No associated EC numbersNo evidence of orthology to BindingDB entries
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 3 | 28 | 26 | 37 |
| disruptive | 23 | 48 | 19 | 87 |
| missense | 22 | 46 | 18 | 80 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 13 | 78 | 24 | 41 |
| disruptive | 33 | 102 | 47 | 153 |
| missense | 27 | 86 | 38 | 120 |
PlasmoDB Total SNPs: 132
Non-coding: 102 | Synonymous: 17 | Nonsynonymous: 13 | Stop Codon: 0
Protein Length: 726 | Molecular Weight (kDa): 83.665
UniProt ID(s): A0A077LQB4, A0A0K2FG53, A0A4D7RU84, A0A4D7RWF4, A0A4D7RWM7, A0A4D7RX47, A0A4D7RXP5, A0A4D7S136, A0A4D7S1N8, A0A4D7S8H5, Q8IDQ2
PDB ID(s): 4ZGC
Isoelectric Point: 5.67
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000210 | BTB/POZ domain |
| InterPro | IPR003131 | Potassium channel tetramerisation-type BTB domain |
| InterPro | IPR006652 | Kelch repeat type 1 |
| InterPro | IPR011333 | SKP1/BTB/POZ domain superfamily |
| InterPro | IPR015915 | Kelch-type beta propeller |
| PFam | PF01344 | Kelch repeat type 1 |
| PFam | PF02214 | Potassium channel tetramerisation-type BTB domain |
| PFam | PF13418 | |
| Superfamily | SSF117281 | Kelch-type beta propeller |
| Superfamily | SSF54695 | SKP1/BTB/POZ domain superfamily |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 24352242 | A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. | Ariey F, Witkowski B, ..., Menard D | 10.1038/nature12876 |
| 25874676 | A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. | Mbengue A, Bhattacharjee S, ..., Haldar K | 10.1038/nature14412 |
| 26503652 | Emergence of Mutations in the K13 Propeller Gene of Plasmodium falciparumIsolates from Dakar, Senegal, in 2013-2014. | Boussaroque A, Fall B, ..., Pradines B | 10.1128/AAC.01346-15 |
| 26535806 | Plasmodium falciparum kelch 13: a potential molecular marker for tacklingartemisinin-resistant malaria parasites. | Mita T, Tachibana S, Hashimoto M, Hirai M | 10.1586/14787210.2016.1106938 |
| 28288121 | A genetic system to study Plasmodium falciparum protein function. | Birnbaum J, Flemming S, ..., Spielmann T | 10.1038/nmeth.4223 |
| 29363540 | Remodeling of the malaria parasite and host human red cell by vesicleamplification that induces artemisinin resistance. | Bhattacharjee S, Coppens I, ..., Haldar K | 10.1182/blood-2017-11-814665 |
| 29976207 | Introduction of F446I mutation in the K13 propeller gene leads to increased ringsurvival rates in Plasmodium falciparum isolates. | Wang J, Huang Y, ..., Pan W | 10.1186/s12936-018-2396-0 |
| 30277206 | Absence of Plasmodium falciparum K13 Propeller Domain Polymorphisms among FieldIsolates Collected from the Brazilian Amazon Basin between 1984 and 2011. | Inoue J, Jovel I, ..., Martensson A | 10.4269/ajtmh.18-0554 |
| 30535043 | Novel pfkelch13 Gene Polymorphism Associates With Artemisinin Resistance inEastern India. | Das S, Manna S, ..., Roy S | 10.1093/cid/ciy1038 |
| 30651111 | Association of mutations in the Plasmodium falciparum Kelch13 gene(Pf3D7_1343700) with parasite clearance rates after artemisinin-basedtreatments-a WWARN individual patient data meta-analysis. | 10.1186/s12916-018-1207-3 | |
| 31009824 | In vitro susceptibility of Plasmodium falciparum isolates from the China-Myanmarborder area to artemisinins and correlation with K13 mutations. | Zhang J, Li N, ..., Yang Z | 10.1016/j.ijpddr.2019.04.002 |
| 31563454 | Importance of kelch 13 C580Y mutation in the studies of artemisinin resistance inPlasmodium falciparum in Greater Mekong Subregion. | Zaw MT, Lin Z, Emran NA | 10.1016/j.jmii.2019.07.006 |
| 31896710 | A Kelch13-defined endocytosis pathway mediates artemisinin resistance in malariaparasites. | Birnbaum J, Scharf S, ..., Spielmann T | 10.1126/science.aax4735 |
| 32098812 | Role of Plasmodium falciparum Kelch 13 Protein Mutations in P. falciparum Populations from Northeastern Myanmar in Mediating Artemisinin Resistance | Siddiqui FA, Boonhok R, ..., Cui L | 10.1128/mBio.01134-19 |
| 32171330 | Targeted deep amplicon sequencing of kelch 13 and cytochrome b in Plasmodiumfalciparum isolates from an endemic African country using the Malaria ResistanceSurveillance (MaRS) protocol. | L'Episcopia M, Kelley J, ..., Talundzic E | 10.1186/s13071-020-4005-7 |
| 32258150 | Sequence Analysis of the K13-Propeller Gene in Artemisinin Challenging Plasmodiumfalciparum Isolates from Malaria Endemic Areas of Odisha, India: A MolecularSurveillance Study. | Rana R, Ranjit M, ..., Das A | 10.1155/2020/8475246 |
| 32310999 | Insights into the intracellular localization, protein associations andartemisinin resistance properties of Plasmodium falciparum K13. | Gnadig NF, Stokes BH, ..., Fidock DA | 10.1371/journal.ppat.1008482 |
| 32394893 | Local emergence in Amazonia of Plasmodium falciparum k13 C580 Y mutants associatedwith in vitro artemisinin resistance | Mathieu LC, Cox H, ..., Musset L | 10.7554/eLife.51015 |
| 32822392 | The lack of K13-propeller mutations associated with artemisinin resistance inPlasmodium falciparum in Democratic Republic of Congo (DRC). | Yobi DM, Kayiba NK, ..., Hayette MP | 10.1371/journal.pone.0237791 |
| 33827592 | Molecular surveillance of drug resistance: Plasmodium falciparum artemisininresistance single nucleotide polymorphisms in Kelch protein propeller (K13)domain from Southern Pakistan. | Ghanchi NK, Qurashi B, Raees H, Beg MA | 10.1186/s12936-021-03715-0 |
| 33933099 | Molecular surveillance of anti-malarial resistance pfcrt, pfmdr1, and pfk13polymorphisms in African Plasmodium falciparum imported parasites to Wuhan,China. | Cheng W, Song X, ..., Li J | 10.1186/s12936-021-03737-8 |
| 34146993 | A review of the frequencies of Plasmodium falciparum Kelch 13 artemisininresistance mutations in Africa. | Ndwiga L, Kimenyi KM, ..., Ochola-Oyier LI | 10.1016/j.ijpddr.2021.06.001 |
| 34279219 | Plasmodium falciparum K13 mutations in Africa and Asia impact artemisininresistance and parasite fitness | Stokes BH, Dhingra SK, ..., Fidock DA | 10.7554/eLife.66277 |
| 34606334 | Mutation in the Plasmodium falciparum BTB/POZ Domain of K13 Protein ConfersArtemisinin Resistance. | Paloque L, Coppee R, ..., Benoit-Vical F | 10.1128/AAC.01320-21 |
| 35551239 | Novel pfk13 polymorphisms in Plasmodium falciparum population in Ghana. | Matrevi SA, Tandoh KZ, ..., Duah-Quashie NO | 10.1038/s41598-022-11790-9 |
| 37208708 | Anti-malarial resistance in Mozambique: Absence of Plasmodium falciparum Kelch 13(K13) propeller domain polymorphisms associated with resistance to artemisinins. | da Silva C, Matias D, ..., Nogueira F | 10.1186/s12936-023-04589-0 |
| 37754284 | Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea. | Mihreteab S, Platon L, ..., Menard D | 10.1056/NEJMoa2210956 |
| 37871569 | Molecular characterization of the Plasmodium falciparum k13 gene helix domain insamples from native communities of Condorcanqui, Amazonas, Peru. | Sandoval-Bances J, Saavedra-Samillan M, ..., Chenet SM | 10.7705/biomedica.6849 |
| 37974079 | Distribution of Plasmodium falciparum K13 gene polymorphisms across transmissionsettings in Ghana | Dieng CC, Morrison V, ..., Lo E | 10.1186/s12879-023-08812-w |
| 38159875 | Artemisinin resistance-associated gene mutations in Plasmodium falciparum: A casestudy of severe malaria from Mozambique | Casanova D, Baptista V, ..., Veiga MI | 10.1016/j.tmaid.2023.102684 |
| 37219373 | A novel Modulator of Ring Stage Translation (MRST) gene alters artemisininsensitivity in Plasmodium falciparum | Simmons C, Gibbons J, ..., Adams JH | 10.1128/msphere.00152-23 |
| 38169593 | Induction of Artesunate Resistance in Plasmodium falciparum 3D7 Strain UsingIntermittent Exposure Method and Comparing P.fk13 Sequence between Susceptibleand Resistant Strains | Barati S, Haghi AM, ..., Etemadi S | 10.18502/ijpa.v18i4.14244 |
| 38196592 | Expansion of Artemisinin Partial Resistance Mutations and Lack of Histidine RichProtein-2 and -3 Deletions in Plasmodium falciparum infections from Rukara,Rwanda | Schreidah C, Giesbrecht D, ..., Karema C | 10.1101/2023.12.17.23300081 |
| 37269964 | Molecular insights into artemisinin resistance in Plasmodium falciparum: Anupdated review | Azmi WA, Rizki AFM, ..., Siregar JE | 10.1016/j.meegid.2023.105460 |
| 38352311 | Evidence of artemisinin partial resistance in North-western Tanzania: clinicaland drug resistance markers study | Ishengoma DS, Mandara CI, ..., Warsame M | 10.1101/2024.01.31.24301954 |
| 37986920 | Country wide surveillance reveals prevalent artemisinin partial resistancemutations with evidence for multiple origins and expansion of high levelsulfadoxine-pyrimethamine resistance mutations in northwest Tanzania | Juliano JJ, Giesbrecht DJ, ..., Ishengoma DS | 10.1101/2023.11.07.23298207 |
| 37640962 | Plasmodium falciparum resistant to artemisinin and diagnostics have emerged inEthiopia | Fola AA, Feleke SM, ..., Bailey JA | 10.1038/s41564-023-01461-4 |
| 38377613 | Burden of Submicroscopic Plasmodium Infections and Detection of kelch13 MutantParasites in Military and Civilian Populations in Papua New Guinea | Pickering PA, Harris I, ..., Cheng Q | 10.4269/ajtmh.23-0508 |
| 37633420 | Artemisinin resistance in P. falciparum: probing the interacting partners ofKelch13 protein in parasite | Atul, Chaudhary P, ..., Pandey KC | 10.1016/j.jgar.2023.08.012 |
| 37494337 | Antimalarial mass drug administration in large populations and the evolution ofdrug resistance | Nguyen TD, Tran TN, ..., Boni MF | 10.1371/journal.pgph.0002200 |
| 38287365 | Molecular surveillance of Kelch 13 polymorphisms in Plasmodium falciparumisolates from Kenya and Ethiopia | Jeang B, Zhong D, ..., Yan G | 10.1186/s12936-023-04812-y |
| 38377612 | Detection of Artemisinin Resistance Marker Kelch-13 469Y in Plasmodiumfalciparum, South Kivu, Democratic Republic of the Congo, 2022 | van Loon W, Bisimwa BC, ..., Bahizire E | 10.4269/ajtmh.23-0740 |
| 37385107 | Multi-omics dissection of stage-specific artemisinin tolerance mechanisms inKelch13-mutant Plasmodium falciparum | Chen J, Gao P, ..., Wang J | 10.1016/j.drup.2023.100978 |
| 37602587 | Molecular detection of drug-resistant Plasmodium falciparum mutants in Assam | Barman L, Sharma A, ..., Saikia L | 10.4103/ijmr.IJMR_2976_20 |
| 37292709 | Parasite proteostasis and artemisinin resistance | Rosenthal M, Ng C | 10.21203/rs.3.rs-2926003/v1 |
| 38105992 | Single cell transcriptional changes across the blood stages of artemisininresistant K13(C580Y) mutant Plasmodium falciparum upon dihydroartemisininexposure | Oduor CI, Cunningham C, ..., Bailey JA | 10.1101/2023.12.06.570387 |
| 38352505 | Selection of artemisinin partial resistance Kelch13 mutations in Uganda in2016-22 was at a rate comparable to that seen previously in South-East Asia | Meier-Scherling CPG, Watson OJ, ..., Bailey JA | 10.1101/2024.02.03.24302209 |
| 38039338 | The Kelch13 compartment contains highly divergent vesicle trafficking proteins inmalaria parasites | Schmidt S, Wichers-Misterek JS, ..., Spielmann T | 10.1371/journal.ppat.1011814 |