Genome location: Pf3D7_13_v3:1,768,122..1,772,620(+)
Genome classification: Core
Product Description: endoplasmic reticulum chaperone GRP170
SignalP Peptide: MRPRFFLFLLFIIYIYNS
# Transmembrane Domains: 0
EC Numbers: None
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005783 | endoplasmic reticulum |
| Component | GO:0034663 | endoplasmic reticulum chaperone complex |
| Function | GO:0005515 | protein binding |
| Process | GO:0071456 | cellular response to hypoxia |
| Process | GO:1903298 | negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway |
| Process | GO:0006950 | response to stress |
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 | 0.63 | 0.71 |
| Trophozoite | no data | 0.95 | 0.52 |
| Schizont | no data | 0.62 | 0.67 |
| Gametocyte | no data | 0.36 | 0.80 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1344200
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: 0.143 | MFS: -2.839 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1357200)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: C0H5H0
"Best" AlphaFill ligand hit: TMO (trimethylamine oxide, Local RMSD=0.03) with 4FL9 (Global RMSD=6.52)
No associated EC numbersNo evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_101811
Most Similar Human Ortholog: J3KSR2
TM-align score: 0.85 | RMSD: 1.07
Seq Identity: 0.03 | Length: 38 / 932
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000149428 | hypoxia up-regulated 1 |
| ENSG00000280682 | hypoxia up-regulated 1 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 63 | 36 | 64 |
| disruptive | 16 | 79 | 63 | 159 |
| missense | 12 | 78 | 60 | 143 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 17 | 110 | 52 | 65 |
| disruptive | 38 | 200 | 103 | 254 |
| missense | 24 | 177 | 87 | 179 |
PlasmoDB Total SNPs: 181
Non-coding: 129 | Synonymous: 32 | Nonsynonymous: 20 | Stop Codon: 0
Protein Length: 932 | Molecular Weight (kDa): 108.185
UniProt ID(s): C0H5H0
PDB ID(s): None
Isoelectric Point: 5.36
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR013126 | Heat shock protein 70 family |
| InterPro | IPR029048 | Heat shock protein 70kD, C-terminal domain superfamily |
| InterPro | IPR043129 | ATPase, nucleotide binding domain |
| PFam | PF00012 | Heat shock protein 70 family |
| Superfamily | SSF100934 | Heat shock protein 70kD, C-terminal domain superfamily |
| Superfamily | SSF53067 | ATPase, nucleotide binding domain |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 19294420 | Return to sender: use of Plasmodium ER retrieval sequences to study proteintransport in the infected erythrocyte and predict putative ER protein families. | Kulzer S, Gehde N, Przyborski JM | 10.1007/s00436-009-1397-x |
| 21191678 | Plasmodium falciparum encodes a single cytosolic type I Hsp40 that functionallyinteracts with Hsp70 and is upregulated by heat shock. | Botha M, Chiang AN, ..., Blatch GL | 10.1007/s12192-010-0250-6 |
| 31087747 | The endoplasmic reticulum chaperone PfGRP170 is essential for asexual developmentand is linked to stress response in malaria parasites. | Kudyba HM, Cobb DW, ..., Muralidharan V | 10.1111/cmi.13042 |
| 35383173 | Mapping SP-C co-chaperone binding sites reveals molecular consequences ofdisease-causing mutations on protein maturation | Pobre-Piza KFR, Mann MJ, Flory AR, Hendershot LM | 10.1038/s41467-022-29478-z |
| 31695116 | Protective effects of seaweed supplemented diet on antioxidant and immuneresponses in European seabass (Dicentrarchus labrax) subjected to bacterial infection | Peixoto MJ, Ferraz R, ..., Ozorio ROA | 10.1038/s41598-019-52693-6 |
| 37905119 | Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions | Mann MJ, Melendez-Suchi C, ..., Buck TM | 10.19.563191 |
| 33525518 | The Role of Non-Canonical Hsp70s (Hsp110/Grp170) in Cancer | Chakafana G, Shonhai A | 10.3390/cells10020254 |
| 36520302 | Nucleotide Exchange Factors for Hsp70 Molecular Chaperones: GrpE, Hsp110/Grp170,HspBP1/Sil1, and BAG Domain Proteins | Bracher A, Verghese J | 10.1007/978-3-031-14740-1_1 |
| 30205291 | Understanding the role of glucose regulated protein 170 (GRP170) as a nucleotideexchange factor through molecular simulations | Pagare PP, Wang H, Wang XY, Zhang Y | 10.1016/j.jmgm.2018.09.001 |
| 34353437 | Targeting heat shock protein 90 for anti-cancer drug development | Aswad A, Liu T | 10.1016/bs.acr.2021.03.006 |
| 35905823 | Grp94 Works Upstream of BiP in Protein Remodeling Under Heat Stress | Amankwah YS, Collins P, ..., Kravats AN | 10.1016/j.jmb.2022.167762 |