PF3D7_1321400 (DHHC8)

Genome location: Pf3D7_13_v3:886,652..889,804(+)

Genome classification: Core

Function and Localization

Product Description: palmitoyltransferase DHHC8, putative

SignalP Peptide: N/A

# Transmembrane Domains: 4

EC Numbers: 2.3.1.- (Transferring groups other than amino-acyl groups.);2.3.1.225 (Protein S-acyltransferase)

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0005794	Golgi apparatus
Component	GO:0005783	endoplasmic reticulum
Function	GO:0016746	acyltransferase activity
Function	GO:0016409	palmitoyltransferase activity
Function	GO:0019706	protein-cysteine S-palmitoyltransferase activity
Function	GO:0008270	zinc ion binding
Process	GO:0018230	peptidyl-L-cysteine S-palmitoylation
Process	GO:0018345	protein palmitoylation
Process	GO:0006612	protein targeting to membrane

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	0.05	0.97
Trophozoite	expressed	0.04	0.97
Schizont	expressed	0.03	0.98
Gametocyte	expressed	0.04	0.98

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1321400

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: 0.287 | MFS: -2.86 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1419700)

Relative Growth Rate: 0.19 ± 0.16
Confidence: 5.06

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1419700)

Modification: Tagged | RMgm-902

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IEA0

"Best" AlphaFill ligand hit: POV (popc, Local RMSD=0.67) with 6BMS (Global RMSD=4.44)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
2.3.1.-	Ex: [myelin-proteolipid] O-palmitoyltransferase	CoAKClArgATPADPEDTAMgCl2CaCl2MnCl2AgNO3CoCl2FeSO4...
2.3.1.225	protein S-acyltransferase	stearoyl-CoAmyristoyl-CoA2-Bromopalmitate2-bromo-palmitateacyl-CoA binding protein

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_104772

Most Similar Human Ortholog: E9PMA5

TM-align score: 0.87 | RMSD: 1.72

Seq Identity: 0.31 | Length: 135 / 313

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000099904	zinc finger DHHC-type palmitoyltransferase 8
ENSG00000156599	zinc finger DHHC-type palmitoyltransferase 5

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	3	18	12	20
disruptive	3	14	14	42
missense	3	13	13	38

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	4	37	14	23
disruptive	6	53	29	56
missense	4	46	25	40

PlasmoDB Total SNPs: 151

Non-coding: 135 | Synonymous: 14 | Nonsynonymous: 2 | Stop Codon: 0

Protein Information

Protein Length: 313 | Molecular Weight (kDa): 36.491

UniProt ID(s): Q8IEA0

PDB ID(s): None

Isoelectric Point: 8.73

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR001594	Palmitoyltransferase, DHHC domain
PFam	PF01529	Palmitoyltransferase, DHHC domain
Superfamily	N/A	N/A

Associated Publications

PMID	Title	Authors	DOI/Link
30761251	Plasmodium palmitoylation machinery engineered in E. coli for high-throughputscreening of palmitoyl acyl-transferase inhibitors.	Yadav P, Ayana R, ..., Singh S	10.1002/2211-5463.12564
22325201	Palmitoylation by DHHC5/8 targets GRIP1 to dendritic endosomes to regulate AMPA-Rtrafficking	Thomas GM, Hayashi T, ..., Huganir RL	10.1016/j.neuron.2011.11.021
30965003	Palmitoylation by Multiple DHHC Enzymes Enhances Dopamine Transporter Function and Stability	Bolland DE, Moritz AE, ..., Foster JD	10.1021/acschemneuro.8b00558
37035671	GCP16 stabilizes the DHHC9 subfamily of protein acyltransferases through aconserved C-terminal cysteine motif	Nguyen PL, Greentree WK, Kawate T, Linder ME	10.3389/fphys.2023.1167094
19556522	Palmitoylation of ATP-binding cassette transporter A1 is essential for itstrafficking and function	Singaraja RR, Kang MH, ..., Hayden MR	10.1161/CIRCRESAHA.108.193011
24068808	DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellarlong-term synaptic depression	Thomas GM, Hayashi T, Huganir RL, Linden DJ	10.1523/JNEUROSCI.1283-13.2013