PF3D7_0709700 (PARE)

Genome location: Pf3D7_07_v3:434,748..436,518(-)

Genome classification: Core

Function and Localization

Product Description: prodrug activation and resistance esterase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 3.1.-.- (Acting on ester bonds.);3.1.1.23 (Acylglycerol lipase)

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0005737	cytoplasm
Component	GO:0016020	membrane
Function	GO:0047372	acylglycerol lipase activity
Function	GO:0016787	hydrolase activity
Function	GO:0016788	hydrolase activity, acting on ester bonds
Function	GO:0016298	lipase activity
Process	GO:0052651	monoacylglycerol catabolic process
Process	GO:0006644	phospholipid metabolic 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	0.13	0.93
Trophozoite	expressed	0.23	0.85
Schizont	expressed	0.34	0.77
Gametocyte	expressed	0.52	0.72

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0709700

Resistome Missense Mutations: G51D, S94R, G206E, H304Y, L323H, P344L, N346Y, I353S, L357P

Resistome Compounds with Missense Mutations: AN13762, AN13956, MMV011438, Pepstatin n-butyl ester

Resistome # Samples with Disruptive Mutations: 26 (13 missense, 12 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 0.913 | MFS: -2.961 | #Insertions: 1

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1220300)

Relative Growth Rate: 1.09 ± 0.18
Confidence: 4.84

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1220300)

Modification: Disrupted | RMgm-3276

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IBZ2

"Best" AlphaFill ligand hit: No AlphaFill hits

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
3.1.-.-	Ex: 5-phospho-D-xylono-1,4-lactonase	paraoxonatropineethylene terephthalatediisopropyl fluorophosphonatebis(2-hydroxyethyl) terephthalic acidphosphoric acid-bis-4-nitrophenyl ester
3.1.1.23	acylglycerol lipase	BRENDA SOAP query unsuccessful

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_100231

Most Similar Human Ortholog: A0A3B3ITT3

TM-align score: 0.86 | RMSD: 1.90

Seq Identity: 0.23 | Length: 242 / 368

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000074416	monoglyceride lipase

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	5	12	9	30
disruptive	4	13	8	49
missense	4	12	7	43

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	7	33	14	25
disruptive	9	34	30	75
missense	7	20	28	61

PlasmoDB Total SNPs: 93

Non-coding: 76 | Synonymous: 11 | Nonsynonymous: 6 | Stop Codon: 0

Protein Information

Protein Length: 368 | Molecular Weight (kDa): 42.358

UniProt ID(s): Q8IBZ2

PDB ID(s): None

Isoelectric Point: 9.52

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR006494	Plasmodium subtelomeric PST-A
InterPro	IPR022742	Serine aminopeptidase, S33
InterPro	IPR029058	Alpha/Beta hydrolase fold
PFam	PF12146	Serine aminopeptidase, S33
Superfamily	SSF53474	Alpha/Beta hydrolase fold

PMID	Title	Authors	DOI/Link
28106035	Esterase mutation is a mechanism of resistance to antimalarial compounds.	Istvan ES, Mallari JP, ..., Goldberg DE	10.1038/ncomms14240
31772212	Functional annotation of serine hydrolases in the asexual erythrocytic stage ofPlasmodium falciparum.	Elahi R, Ray WK, ..., Klemba M	10.1038/s41598-019-54009-0