About Gene List

PF3D7_1116800 (HSP101)

Genome location: Pf3D7_11_v3:635,806..641,374(-)

Genome classification: Core

Function and Localization

Product Description: heat shock protein 101

SignalP Peptide: MTRRYLKYYIFVTLLFFVQVINNVLC

# Transmembrane Domains: 1

EC Numbers: None

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020036 Maurer's cleft
Component GO:0097619 PTEX complex
Component GO:0020007 apical complex
Component GO:0005737 cytoplasm
Component GO:0005783 endoplasmic reticulum
Component GO:1903561 extracellular vesicle
Component GO:0020026 merozoite dense granule
Component GO:0005634 nucleus
Component GO:0020003 symbiont-containing vacuole
Component GO:0020005 symbiont-containing vacuole membrane
Function GO:0016887 ATP hydrolysis activity
Function GO:0003723 RNA binding
Function GO:0005515 protein binding
Process GO:0034605 cellular response to heat
Process GO:0043335 protein unfolding
Process GO:0009408 response to heat
Process GO:0006986 response to unfolded protein
Process GO:0044053 translocation of peptides or proteins into host cell cytoplasm

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 2.93 0.08
Trophozoite expressed 1.08 0.47
Schizont expressed 0.59 0.69
Gametocyte possibly expressed 0.77 0.60

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1116800

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: 0.119 | MFS: -3.014 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0931200)

  • Relative Growth Rate: 0.11 ± 0.29
  • Confidence: 3.83

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0931200)

Modification: Tagged | RMgm-5275

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IIJ8

"Best" AlphaFill ligand hit: ANP (phosphoaminophosphonic acid-adenylate ester, Local RMSD=0.34) with 1QVR (Global RMSD=5.71)

No associated EC numbers

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_100223

Most Similar Human Ortholog: A0A2R8Y602

TM-align score: 0.61 | RMSD: 4.33

Seq Identity: 0.31 | Length: 282 / 906

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000162129 caseinolytic mitochondrial matrix peptidase chaperone subunit B

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 10 52 33 63
disruptive 8 24 16 40
missense 8 22 14 32

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 27 111 32 40
disruptive 15 68 43 127
missense 13 51 35 92

PlasmoDB Total SNPs: 180

Non-coding: 151 | Synonymous: 22 | Nonsynonymous: 7 | Stop Codon: 0

Protein Information

Protein Length: 906 | Molecular Weight (kDa): 102.874

UniProt ID(s): Q8IIJ8, Q9NFG9

PDB ID(s): 4IOD, 4IRF, 6E10, 6E11

Isoelectric Point: 9.66

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001270 ClpA/B family
InterPro IPR003593 AAA+ ATPase domain
InterPro IPR003959 ATPase, AAA-type, core
InterPro IPR004176 Clp, repeat (R) domain
InterPro IPR018368 ClpA/B, conserved site 1
InterPro IPR019489 Clp ATPase, C-terminal
InterPro IPR027417 P-loop containing nucleoside triphosphate hydrolase
InterPro IPR028299 ClpA/B, conserved site 2
InterPro IPR036628 Clp, N-terminal domain superfamily
InterPro IPR041546 ClpA/ClpB, AAA lid domain
PFam PF00004 ATPase, AAA-type, core
PFam PF02861 Clp, repeat (R) domain
PFam PF07724 ATPase, AAA-type, core
PFam PF10431 Clp ATPase, C-terminal
PFam PF17871 ClpA/ClpB, AAA lid domain
Superfamily SSF52540 P-loop containing nucleoside triphosphate hydrolase
Superfamily SSF81923 Clp, N-terminal domain superfamily

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
16267556 A protein interaction network of the malaria parasite Plasmodium falciparum. LaCount DJ, Vignali M, ..., Hughes RE 10.1038/nature04104
19536257 A newly discovered protein export machine in malaria parasites. de Koning-Ward TF, Gilson PR, ..., Crabb BS 10.1038/nature08104
20887733 The Clp chaperones and proteases of the human malaria parasite Plasmodiumfalciparum. El Bakkouri M, Pow A, ..., Houry WA 10.1016/j.jmb.2010.09.051
22253438 Biosynthesis, localization, and macromolecular arrangement of the Plasmodiumfalciparum translocon of exported proteins (PTEX). Bullen HE, Charnaud SC, ..., Gilson PR 10.1074/jbc.M111.328591
22970262 An exported heat shock protein 40 associates with pathogenesis-related knobs inPlasmodium falciparum infected erythrocytes. Acharya P, Chaubey S, Grover M, Tatu U 10.1371/journal.pone.0044605
25043010 PTEX component HSP101 mediates export of diverse malaria effectors into hosterythrocytes. Beck JR, Muralidharan V, Oksman A, Goldberg DE 10.1038/nature13574
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
29487358 PV1, a novel Plasmodium falciparum merozoite dense granule protein, interactswith exported protein in infected erythrocytes. Morita M, Nagaoka H, ..., Takashima E 10.1038/s41598-018-22026-0
29637707 The malaria PTEX component PTEX88 interacts most closely with HSP101 at thehost-parasite interface. Chisholm SA, Kalanon M, ..., de Koning-Ward TF 10.1111/febs.14463
30150771 Malaria parasite translocon structure and mechanism of effector export. Ho CM, Beck JR, ..., Zhou ZH 10.1038/s41586-018-0469-4
30379851 Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. Briquet S, Ourimi A, ..., Vaquero C 10.1371/journal.pone.0205596
31164473 Uncoupling the Threading and Unfoldase Actions of Plasmodium H SP101 Reveals Differences in Export between Soluble and Insoluble Proteins Matthews KM, Kalanon M, de Koning-Ward TF 10.1128/mBio.01106-19
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
33906926 Functional Characterization of the m(6)A-Dependent Translational Modulator PfYTH Sinha A, Baumgarten S, ..., Scherf A 10.1128/mBio.00661-21
35192672 A revised mechanism for how Plasmodium falciparum recruits and exports proteinsinto its erythrocytic host cell. Gabriela M, Matthews KM, ..., Gilson PR 10.1371/journal.ppat.1009977
37552754 Knock-sideways by inducible ER retrieval enables a unique approach for studyingPlasmodium-secreted proteins Fierro MA, Hussain T, Campin LJ, Beck JR 10.1073/pnas.2308676120
36238365 Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake andmetabolism in Plasmodium falciparum Gupta P, Pandey R, ..., Malhotra P 10.1096/fba.2022-00021
36445080 The PTEX Pore Component EXP2 Is Important for Intrahepatic Development during the Plasmodium Liver Stage Hussain T, Linera-Gonzalez J, ..., Beck JR 10.1128/mbio.03096-22
37926971 Sequence elements within the PEXEL motif and its downstream region modulate PTEX-dependent protein export in Plasmodium falciparum Gabriela M, Barnes CBG, ..., Gilson PR 10.1111/tra.12922