PF3D7_1317100 (MCM4)

Genome location: Pf3D7_13_v3:711,294..715,548(+)

Genome classification: Core

Function and Localization

Product Description: DNA replication licensing factor MCM4

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 3.6.4.12 (DNA helicase)

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0042555	MCM complex
Component	GO:0005634	nucleus
Function	GO:0003688	DNA replication origin binding
Function	GO:0003697	single-stranded DNA binding
Process	GO:0006270	DNA replication initiation
Process	GO:0006271	DNA strand elongation involved in DNA replication
Process	GO:0006268	DNA unwinding involved in DNA replication
Process	GO:0000727	double-strand break repair via break-induced replication
Process	GO:1902975	mitotic DNA replication initiation
Process	GO:0006267	pre-replicative complex assembly involved in nuclear cell cycle DNA replication

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	not expressed	0.10	0.95
Trophozoite	expressed	0.79	0.58
Schizont	expressed	0.59	0.66
Gametocyte	expressed	0.63	0.66

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1317100

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: 0.16 | MFS: -2.972 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1415600)

Relative Growth Rate: 0.10 ± nan
Confidence: 1.00

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IEE5

"Best" AlphaFill ligand hit: ADP (adenosine-5'-diphosphate, Local RMSD=0.21) with 4R7Y (Global RMSD=0.82)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
3.6.4.12	DNA helicase	No BRENDA inhibitors

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_101805

Most Similar Human Ortholog: A0A3B3IRR8

TM-align score: 0.93 | RMSD: 1.59

Seq Identity: 0.55 | Length: 189 / 1005

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000104738	minichromosome maintenance complex component 4

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	12	61	18	61
disruptive	4	35	25	64
missense	3	32	23	51

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	28	109	35	40
disruptive	18	95	73	173
missense	13	72	54	116

PlasmoDB Total SNPs: 143

Non-coding: 97 | Synonymous: 30 | Nonsynonymous: 14 | Stop Codon: 2

Protein Information

Protein Length: 1005 | Molecular Weight (kDa): 115.217

UniProt ID(s): Q8IEE5, Q9GR06

PDB ID(s): None

Isoelectric Point: 6.29

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR001208	MCM domain
InterPro	IPR008047	Mini-chromosome maintenance complex protein 4
InterPro	IPR012340	Nucleic acid-binding, OB-fold
InterPro	IPR018525	Mini-chromosome maintenance, conserved site
InterPro	IPR027417	P-loop containing nucleoside triphosphate hydrolase
InterPro	IPR031327	Mini-chromosome maintenance protein
InterPro	IPR033762	MCM OB domain
InterPro	IPR041562	MCM, AAA-lid domain
PFam	PF00493	MCM domain
PFam	PF17207	MCM OB domain
PFam	PF17855	MCM, AAA-lid domain
Superfamily	SSF50249	Nucleic acid-binding, OB-fold
Superfamily	SSF52540	P-loop containing nucleoside triphosphate hydrolase

PMID	Title	Authors	DOI/Link
16842352	Analogous expression pattern of Plasmodium falciparum replication initiationproteins PfMCM4 and PfORC1 during the asexual and sexual stages ofintraerythrocytic developmental cycle.	Gupta A, Mehra P, ..., Dhar SK	10.1111/j.1574-6968.2006.00324.x
30379851	Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation.	Briquet S, Ourimi A, ..., Vaquero C	10.1371/journal.pone.0205596