Genome location: Pf3D7_08_v3:1,364,640..1,369,862(-)
Genome classification: Core
Product Description: heat shock protein 70
SignalP Peptide: MKTKICSYIHYIVLFLIATTTVHT
# Transmembrane Domains: 1
EC Numbers: None
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020036 | Maurer's cleft |
| Component | GO:0005737 | cytoplasm |
| Component | GO:1903561 | extracellular vesicle |
| Component | GO:0030430 | host cell cytoplasm |
| Component | GO:0044164 | host cell cytosol |
| Component | GO:0005634 | nucleus |
| Component | GO:0032991 | protein-containing complex |
| Component | GO:0020003 | symbiont-containing vacuole |
| Function | GO:0005524 | ATP binding |
| Function | GO:0016887 | ATP hydrolysis activity |
| Function | GO:0003723 | RNA binding |
| Function | GO:0031072 | heat shock protein binding |
| Function | GO:0051787 | misfolded protein binding |
| Function | GO:0005515 | protein binding |
| Function | GO:0044183 | protein folding chaperone |
| Function | GO:0051082 | unfolded protein binding |
| Process | GO:0034620 | cellular response to unfolded protein |
| Process | GO:0051085 | chaperone cofactor-dependent protein refolding |
| Process | GO:0020035 | cytoadherence to microvasculature, mediated by symbiont protein |
| Process | GO:0042026 | protein refolding |
| Process | GO:0006986 | response to unfolded protein |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | no data | N/A | N/A |
| Ring | no data | 2.67 | 0.21 |
| Trophozoite | no data | 1.88 | 0.25 |
| Schizont | no data | 0.61 | 0.70 |
| Gametocyte | no data | 0.66 | 0.70 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0831700
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 1 | MFS: 0.585 | #Insertions: 5
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0711900)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: P12078
"Best" AlphaFill ligand hit: TMO (trimethylamine oxide, Local RMSD=0.19) with 4FL9 (Global RMSD=6.80)
No associated EC numbersNo evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_100083
Most Similar Human Ortholog: E9PK54
TM-align score: 0.99 | RMSD: 0.63
Seq Identity: 0.77 | Length: 183 / 679
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000044574 | heat shock protein family A (Hsp70) member 5 |
| ENSG00000109971 | heat shock protein family A (Hsp70) member 8 |
| ENSG00000126803 | heat shock protein family A (Hsp70) member 2 |
| ENSG00000173110 | heat shock protein family A (Hsp70) member 6 |
| ENSG00000204388 | heat shock protein family A (Hsp70) member 1B |
| ENSG00000204389 | heat shock protein family A (Hsp70) member 1A |
| ENSG00000204390 | heat shock protein family A (Hsp70) member 1 like |
| ENSG00000206383 | heat shock protein family A (Hsp70) member 1 like |
| ENSG00000212866 | heat shock protein family A (Hsp70) member 1B |
| ENSG00000215328 | heat shock protein family A (Hsp70) member 1A |
| ENSG00000224501 | heat shock protein family A (Hsp70) member 1B |
| ENSG00000226704 | heat shock protein family A (Hsp70) member 1 like |
| ENSG00000231555 | heat shock protein family A (Hsp70) member 1B |
| ENSG00000232804 | heat shock protein family A (Hsp70) member 1B |
| ENSG00000234258 | heat shock protein family A (Hsp70) member 1 like |
| ENSG00000234475 | heat shock protein family A (Hsp70) member 1A |
| ENSG00000235941 | heat shock protein family A (Hsp70) member 1A |
| ENSG00000236251 | heat shock protein family A (Hsp70) member 1 like |
| ENSG00000237724 | heat shock protein family A (Hsp70) member 1A |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 1 | 0 | 1 | 1 |
| disruptive | 0 | 2 | 2 | 4 |
| missense | 0 | 2 | 2 | 4 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 1 | 2 | 0 | 4 |
| disruptive | 1 | 2 | 6 | 12 |
| missense | 1 | 1 | 6 | 9 |
PlasmoDB Total SNPs: 198
Non-coding: 176 | Synonymous: 14 | Nonsynonymous: 8 | Stop Codon: 0
Protein Length: 679 | Molecular Weight (kDa): 75.053
PDB ID(s): 6RZQ, 6S02, 6ZHI, 7NQR, 7NQS, 7NQU, 7NQZ, 7OOE, 7OOG, 7OOH, 7P31
Isoelectric Point: 5.44
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR013126 | Heat shock protein 70 family |
| InterPro | IPR018181 | Heat shock protein 70, conserved site |
| InterPro | IPR029047 | Heat shock protein 70kD, peptide-binding domain superfamily |
| InterPro | IPR029048 | Heat shock protein 70kD, C-terminal domain superfamily |
| InterPro | IPR043129 | ATPase, nucleotide binding domain |
| PFam | PF00012 | Heat shock protein 70 family |
| Superfamily | SSF100920 | Heat shock protein 70kD, peptide-binding domain superfamily |
| Superfamily | SSF100934 | Heat shock protein 70kD, C-terminal domain superfamily |
| Superfamily | SSF53067 | ATPase, nucleotide binding domain |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 20482550 | Parasite-encoded Hsp40 proteins define novel mobile structures in the cytosol ofthe P. falciparum-infected erythrocyte. | Kulzer S, Rug M, ..., Przyborski JM | 10.1111/j.1462-5822.2010.01477.x |
| 22925632 | Plasmodium falciparum-encoded exported hsp70/hsp40 chaperone/co-chaperonecomplexes within the host erythrocyte. | Kulzer S, Charnaud S, ..., Przyborski JM | 10.1111/j.1462-5822.2012.01840.x |
| 23340228 | Identification of an exported heat shock protein 70 in Plasmodium falciparum. | Grover M, Chaubey S, Ranade S, Tatu U | 10.1051/parasite/2012002 |
| 24028577 | Plasmodium falciparum Hsp70-x: a heat shock protein at the host-parasiteinterface. | Hatherley R, Blatch GL, Bishop OT | 10.1080/07391102.2013.834849 |
| 26083397 | Overexpression, Purification and Characterisation of the Plasmodium falciparumHsp70-z (PfHsp70-z) Protein. | Zininga T, Achilonu I, ..., Shonhai A | 10.1371/journal.pone.0129445 |
| 26845441 | The Malarial Exported PFA0660w Is an Hsp40 Co-Chaperone of PfHsp70-x. | Daniyan MO, Boshoff A, ..., Blatch GL | 10.1371/journal.pone.0148517 |
| 27824087 | Trafficking of the exported P. falciparum chaperone PfHsp70x. | Rhiel M, Bittl V, ..., Przyborski JM | 10.1038/srep36174 |
| 28732045 | The exported chaperone Hsp70-x supports virulence functions for Plasmodiumfalciparum blood stage parasites. | Charnaud SC, Dixon MWA, ..., Gilson PR | 10.1371/journal.pone.0181656 |
| 28944300 | Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyanclinical isolate defines a core parasite secretome. | Abdi A, Yu L, ..., Rayner J | 10.12688/wellcomeopenres.11910.2 |
| 30183110 | Structural and biochemical characterization of Plasmodium falciparum Hsp70-xreveals functional versatility of its C-terminal EEVN motif. | Mabate B, Zininga T, ..., Shonhai A | 10.1002/prot.25600 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 30804381 | Cholesterol bound Plasmodium falciparum co-chaperone 'PFA0660w' complexes withmajor virulence factor 'PfEMP1' via chaperone 'PfHsp70-x'. | Behl A, Kumar V, ..., Mishra PC | 10.1038/s41598-019-39217-y |
| 31430682 | Structural insights into the binding mechanism of Plasmodium falciparum exportedHsp40-Hsp70 chaperone pair. | Behl A, Mishra PC | 10.1016/j.compbiolchem.2019.107099 |
| 33906926 | Functional Characterization of the m(6)A-Dependent Translational Modulator PfYTH | Sinha A, Baumgarten S, ..., Scherf A | 10.1128/mBio.00661-21 |
| 29211247 | Immunoproteomics of Plasmodium falciparum-infected red blood cell membranefractions | Cabral FJ, Vianna LG, ..., Wunderlich G | 10.1590/0074-02760170041 |
| 28959740 | The Exported Chaperone PfHsp70x Is Dispensable for the Plasmodium falciparumIntraerythrocytic Life Cycle | Cobb DW, Florentin A, ..., Muralidharan V | 10.1128/mSphere.00363-17 |
| 27019089 | Proteomic analysis reveals novel proteins associated with the Plasmodium proteinexporter PTEX and a loss of complex stability upon truncation of the core PTEXcomponent, PTEX150 | Elsworth B, Sanders PR, ..., Gilson PR | 10.1111/cmi.12596 |
| 31690116 | The Plasmodium falciparum Hsp70-x chaperone assists the heat stress response ofthe malaria parasite | Day J, Passecker A, Beck HP, Vakonakis I | 10.1096/fj.201901741R |
| 37074531 | Human granzyme B binds Plasmodium falciparum Hsp70-x and mediates antiplasmodialactivity in vitro | Ramatsui L, Dongola TH, ..., Shonhai A | 10.1007/s12192-023-01339-8 |
| 31717270 | Establishing Computational Approaches Towards Identifying Malarial AllostericModulators: A Case Study of Plasmodium falciparum Hsp70s | Amusengeri A, Astl L, ..., Tastan Bishop O | 10.3390/ijms20225574 |