About Gene List

PF3D7_0624000 (HK)

Genome location: Pf3D7_06_v3:980,208..983,258(+)

Genome classification: Core

Function and Localization

Product Description: hexokinase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.1.- (Phosphotransferases with an alcohol group as acceptor.);2.7.1.1 (Hexokinase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020036 Maurer's cleft
Component GO:0036396 RNA N6-methyladenosine methyltransferase complex
Component GO:0005829 cytosol
Component GO:0005739 mitochondrion
Component GO:0005634 nucleus
Function GO:0008865 fructokinase activity
Function GO:0004340 glucokinase activity
Function GO:0004396 hexokinase activity
Function GO:0019158 mannokinase activity
Process GO:0001678 cellular glucose homeostasis
Process GO:0051156 glucose 6-phosphate metabolic process
Process GO:0006096 glycolytic process
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 0.32 0.84
Trophozoite expressed 0.66 0.63
Schizont expressed 0.20 0.85
Gametocyte expressed 0.30 0.82

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0624000

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.462 | MFS: -2.565 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1122900)

  • Relative Growth Rate: 0.08 ± 0.20
  • Confidence: 4.60

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q02155

"Best" AlphaFill ligand hit: NHE (2-[n-cyclohexylamino]ethane sulfonic acid, Local RMSD=0.36) with 3O1W (Global RMSD=4.68)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.1.- Ex: hamamelose kinase ATPADPCTPUDPAMPGTPGDPUTPCDPITPIDPcAMP...
2.7.1.1 hexokinase BRENDA SOAP query unsuccessful

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
Q38C42 Phosphotransferase Trypanosoma brucei OMA, OrthoDB, OrthoMCL Glucosamine derivative, 6Glucosamine derivative, 8
P52792 Hexokinase-4 OMA, OrthoDB US9409900, 6US9409900, 13US9409900, 65US9409900, 78...
Q38C41 Phosphotransferase Trypanosoma brucei OrthoDB, OrthoMCL med.21724, Compound 153MLS000055225lipoic acid (LA)MLS000550500...
P35557 Hexokinase-4 Homo sapiens OrthoDB benzamide derivative, 6benzamide derivative, 13hbenzamide derivative, 13lbenzamide derivative, 13q...
Q2TB90 Hexokinase HKDC1 [W721R] Homo sapiens OrthoDB MLS000084034cid_68261MLS000052721prostaglandin F2 methyl ester...
P52789 Hexokinase-2 OrthoDB CHEMBL3805703CHEMBL3805460CHEMBL3804930CHEMBL3805765...
P17712 Hexokinase-4 Rattus norvegicus OrthoDB CHEMBL178370CHEMBL178308CHEMBL359618CHEMBL360155...
P19367 Hexokinase-1 Homo sapiens OrthoDB MLS000084626MLS000339491MLS000681605MLS001002736...

Orthology Information

Ortholog Group (OrthoMCL): OG6_100418

Most Similar Human Ortholog: E9PB90

TM-align score: 0.84 | RMSD: 2.24

Seq Identity: 0.31 | Length: 440 / 493

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000156510 hexokinase domain containing 1
ENSG00000156515 hexokinase 1
ENSG00000159399 hexokinase 2
ENSG00000160883 hexokinase 3

Protein Information

Protein Length: 493 | Molecular Weight (kDa): 55.261

UniProt ID(s): C6KT76, Q02155

PDB ID(s): None

Isoelectric Point: 7.05

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001312 Hexokinase
InterPro IPR019807 Hexokinase, binding site
InterPro IPR022672 Hexokinase, N-terminal
InterPro IPR022673 Hexokinase, C-terminal
InterPro IPR043129 ATPase, nucleotide binding domain
PFam PF00349 Hexokinase, N-terminal
PFam PF03727 Hexokinase, C-terminal
Superfamily SSF53067 ATPase, nucleotide binding domain

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 5 31 7 30
disruptive 1 6 3 13
missense 1 6 3 9

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 16 34 17 25
disruptive 2 18 13 43
missense 1 12 10 28

PlasmoDB Total SNPs: 134

Non-coding: 127 | Synonymous: 6 | Nonsynonymous: 1 | Stop Codon: 0

Associated Publications

PMID Title Authors DOI/Link
12368867 Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. Hall N, Pain A, ..., Barrell BG 10.1038/nature01095
16267556 A protein interaction network of the malaria parasite Plasmodium falciparum. LaCount DJ, Vignali M, ..., Hughes RE 10.1038/nature04104
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
23954294 Studies with the Plasmodium falciparum hexokinase reveal that PfHT limits therate of glucose entry into glycolysis. Tjhin ET, Staines HM, ..., Saliba KJ 10.1016/j.febslet.2013.07.052
27458230 Identification of Novel Plasmodium falciparum Hexokinase Inhibitors withAntiparasitic Activity. Davis MI, Patrick SL, ..., Morris JC 10.1128/AAC.00914-16
31384004 Transcriptome-wide dynamics of extensive m(6)A mRNA methylation during Plasmodiumfalciparum blood-stage development. Baumgarten S, Bryant JM, ..., Scherf A 10.1038/s41564-019-0521-7
31631203 A network-based approach reveals novel invasion and Maurer's clefts-relatedproteins in Plasmodium falciparum. Das D, Krishnan SR, Roy A, Bulusu G 10.1039/c9mo00124g
37628920 Structural Analysis of Plasmodium falciparum Hexokinase Provides Novel Information about Catalysis Due to a Plasmodium-Specific Insertion Dillenberger M, Werner AD, ..., Fritz-Wolf K 10.3390/ijms241612739
38423908 Potential inhibitory effect of Auricularia auricula polysaccharide on advancedglycation end-products (AGEs) Gong P, Pei S, ..., Guo Y 10.1016/j.ijbiomac.2024.129856