PF3D7_0817000 (UBA3)

Genome location: Pf3D7_08_v3:772,568..773,737(+)

Genome classification: Core

Function and Localization

Product Description: NEDD8-activating enzyme E1 catalytic subunit, putative

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 6.2.1.45 (E1 ubiquitin-activating enzyme);6.2.1.64 (E1 NEDD8-activating enzyme)

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0005737	cytoplasm
Component	GO:0005634	nucleus
Function	GO:0019781	NEDD8 activating enzyme activity
Process	GO:0032446	protein modification by small protein conjugation
Process	GO:0045116	protein neddylation

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

Stage	LR class	MCA mean	MCA prop. zeros
Sporozoite	not expressed	N/A	N/A
Ring	not expressed	0.01	1.00
Trophozoite	expressed	0.04	0.97
Schizont	possibly expressed	0.01	1.00
Gametocyte	possibly expressed	0.06	0.96

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0817000

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: 0.12 | MFS: -3.028 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: C0H4V1

"Best" AlphaFill ligand hit: AMP (adenosine monophosphate, Local RMSD=0.74) with 7SOL (Global RMSD=3.26)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
6.2.1.45	E1 ubiquitin-activating enzyme	LMO2PYR-41AtMUB3largazoletrichostatin Aginsenoside Reginsenoside Rg1[ubiquitin carrier protein Ubc4]-L-cysteine5'-[[(L-cysteinylglycylglycyl)sulfamoyl]amino]-5'-deoxyadenosine1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester(5R,8S)-11-ethenyl-5-methyl-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione...
6.2.1.64	E1 NEDD8-activating enzyme	MLN4924TAS4464

Orthology to BindingDB Entries:

UniProt	Protein Name	Species	Homology Source	BindingDB Ligands
Q8TBC4	NEDD8-activating enzyme E1 catalytic subunit		OMA, OrthoDB	MITOXANTRONEPevonedistatCHEMBL4878088CHEMBL4865086...
A0AVT1	Ubiquitin-like modifier-activating enzyme 6	Homo sapiens	OrthoDB	US9593121, 1-01US9593121, I-02US9593121, I-03US9593121, I-04...
P41226	Ubiquitin-like modifier-activating enzyme 7	Homo sapiens	OrthoDB	CHEMBL2017005
Q9UBT2	SUMO-activating enzyme subunit 2		OrthoDB	US9796725, Compound I-001US9796725, Compound I-098US9796725, Compound I-003US9796725, Compound I-004...
P22314	Ubiquitin-like modifier-activating enzyme 1	Homo sapiens	OrthoDB	Compound ICompound ICompound IUS9796725, Compound I-001...

Orthology Information

Ortholog Group (OrthoMCL): OG6_101845

Most Similar Human Ortholog: Q8TBC4

TM-align score: 0.68 | RMSD: 4.06

Seq Identity: 0.25 | Length: 315 / 389

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000144744	ubiquitin like modifier activating enzyme 3

Protein Information

Protein Length: 389 | Molecular Weight (kDa): 45.703

UniProt ID(s): C0H4V1

PDB ID(s): None

Isoelectric Point: 7.51

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR000594	THIF-type NAD/FAD binding fold
InterPro	IPR030468	NEDD8-activating enzyme E1 catalytic subunit
InterPro	IPR035985	Ubiquitin-activating enzyme
PFam	PF00899	THIF-type NAD/FAD binding fold
Superfamily	SSF69572	Ubiquitin-activating enzyme

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	3	20	11	19
disruptive	3	19	10	36
missense	3	19	10	28

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	4	31	16	27
disruptive	11	34	24	70
missense	8	29	17	49

PlasmoDB Total SNPs: 41

Non-coding: 0 | Synonymous: 34 | Nonsynonymous: 7 | Stop Codon: 0