PF3D7_0306200 (AHA1)

Genome location: Pf3D7_03_v3:291,924..295,013(+)

Genome classification: Core

Function and Localization

Product Description: activator of Hsp90 ATPase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: None

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0005829	cytosol
Function	GO:0001671	ATPase activator activity
Function	GO:0051879	Hsp90 protein binding
Process	GO:0032781	positive regulation of ATP-dependent activity
Process	GO:0006457	protein folding

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage	LR class	MCA mean	MCA prop. zeros
Sporozoite	possibly expressed	N/A	N/A
Ring	expressed	0.29	0.86
Trophozoite	expressed	0.61	0.66
Schizont	expressed	0.05	0.97
Gametocyte	expressed	0.95	0.55

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0306200

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: Mutable in CDS

MIS: 0.854 | MFS: -3.363 | #Insertions: 1

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0404600)

Relative Growth Rate: 0.97 ± 0.12
Confidence: 5.61

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0404600)

Modification: Disrupted | RMgm-1850

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: O97244

"Best" AlphaFill ligand hit: DCM (2'-deoxycytidine-5'-monophosphate, Local RMSD=0.68) with 2JAT (Global RMSD=17.04)

No associated EC numbers

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_114697

No human ortholog(s)

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	1	13	6	19
disruptive	5	39	26	56
missense	5	38	24	54

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	4	24	19	24
disruptive	13	77	34	97
missense	8	72	32	74

PlasmoDB Total SNPs: 135

Non-coding: 123 | Synonymous: 4 | Nonsynonymous: 7 | Stop Codon: 1

Protein Information

Protein Length: 349 | Molecular Weight (kDa): 41.591

UniProt ID(s): O97244, Q689C6

PDB ID(s): None

Isoelectric Point: 4.96

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR015310	Activator of Hsp90 ATPase, N-terminal
InterPro	IPR036338	Activator of Hsp90 ATPase, Aha1
InterPro	IPR039981	Activator of 90kDa heat shock protein ATPase-like
PFam	PF09229	Activator of Hsp90 ATPase, N-terminal
Superfamily	SSF103111	Activator of Hsp90 ATPase, Aha1

Associated Publications

PMID	Title	Authors	DOI/Link
10448855	The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum.	Bowman S, Lawson D, ..., Barrell BG	10.1038/22964
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
22100910	Molecular analysis of Plasmodium falciparum co-chaperone Aha1 supports itsinteraction with and regulation of Hsp90 in the malaria parasite.	Chua CS, Low H, Lehming N, Sim TS	10.1016/j.biocel.2011.10.021
33538363	Febrile temperature causes transcriptional downregulation of Plasmodiumfalciparum Sirtuins through Hsp90-dependent epigenetic modification.	Tabassum W, Bhattacharyya S, Varunan SM, Bhattacharyya MK	10.1111/mmi.14692
36516069	A Split Renilla Luciferase Complementation Assay for the Evaluation of Hsp90/Aha1Complex Disruptors and Their Activity at the Aha1 C-Terminal Domain	Keegan BM, Blagg BSJ	10.1021/acschembio.2c00854
37515325	Aha1 regulates Hsp90's conformation and function in a stoichiometry-dependent way	Mondol T, Silbermann LM, ..., Hugel T	10.1016/j.bpj.2023.07.020
37228112	Hsp90 mutants with distinct defects provide novel insights into cochaperone regulation of the folding cycle	Mercier R, Yama D, LaPointe P, Johnson JL	10.1371/journal.pgen.1010772