Genome location: Pf3D7_13_v3:2,615,836..2,618,677(-)
Genome classification: Core
Product Description: adenylyltransferase and sulfurtransferase UBA4, putative
SignalP Peptide: N/A
# Transmembrane Domains: 2
EC Numbers: 2.7.7.- (Nucleotidyltransferases.);2.8.1.- (Sulfurtransferases.);6.2.1.45 (E1 ubiquitin-activating enzyme)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0016020 | membrane |
| Function | GO:0016887 | ATP hydrolysis activity |
| Function | GO:0042292 | URM1 activating enzyme activity |
| Function | GO:0003824 | catalytic activity |
| Function | GO:0016779 | nucleotidyltransferase activity |
| Function | GO:0070733 | protein adenylyltransferase activity |
| Function | GO:0016783 | sulfurtransferase activity |
| Function | GO:0004792 | thiosulfate sulfurtransferase activity |
| Process | GO:0010564 | regulation of cell cycle process |
| Process | GO:0034227 | tRNA thio-modification |
| Process | GO:0030433 | ubiquitin-dependent ERAD pathway |
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 | 0.12 | 0.94 |
| Trophozoite | expressed | 0.20 | 0.87 |
| Schizont | expressed | 0.04 | 0.98 |
| Gametocyte | expressed | 0.23 | 0.86 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1365400
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.12 | MFS: -3.048 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1141200)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8ID54
"Best" AlphaFill ligand hit: POP (pyrophosphate 2-, Local RMSD=0.59) with 6DC6 (Global RMSD=7.96)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.7.7.- | Ex: 2-hydroxyethylphosphonate cytidylyltransferase | ADPAMPUTPKClNAD+NADP+NaAD+ppGpppppGppsuraminADPribosecisplatin... |
| 2.8.1.- | Ex: L-aspartate semialdehyde sulfurtransferase | NEMSDSH2SCaCl2SO42-SO32-malateanionssulfitecitrateSulfidelipoate... |
| 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... |
No evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_100543
Most Similar Human Ortholog: O95396
TM-align score: 0.54 | RMSD: 2.25
Seq Identity: 0.31 | Length: 265 / 584
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000124217 | molybdenum cofactor synthesis 3 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 41 | 16 | 52 |
| disruptive | 26 | 72 | 37 | 96 |
| missense | 15 | 62 | 30 | 73 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 19 | 80 | 25 | 40 |
| disruptive | 44 | 149 | 70 | 147 |
| missense | 27 | 115 | 53 | 100 |
PlasmoDB Total SNPs: 151
Non-coding: 95 | Synonymous: 34 | Nonsynonymous: 22 | Stop Codon: 0
Protein Length: 584 | Molecular Weight (kDa): 68.388
UniProt ID(s): Q8ID54
PDB ID(s): None
Isoelectric Point: 9.23
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000594 | THIF-type NAD/FAD binding fold |
| InterPro | IPR035985 | Ubiquitin-activating enzyme |
| InterPro | IPR036873 | Rhodanese-like domain superfamily |
| PFam | PF00899 | THIF-type NAD/FAD binding fold |
| Superfamily | SSF52821 | Rhodanese-like domain superfamily |
| Superfamily | SSF69572 | Ubiquitin-activating enzyme |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 19502583 | An unusual ERAD-like complex is targeted to the apicoplast of Plasmodiumfalciparum. | Spork S, Hiss JA, ..., Przyborski JM | 10.1128/EC.00083-09 |
| 29718331 | The Uba4 domain interplay is mediated via a thioester that is critical for tRNA thiolation through Urm1 thiocarboxylation | Termathe M, Leidel SA | 10.1093/nar/gky312 |
| 28830344 | Tum1 is involved in the metabolism of sterol esters in Saccharomyces cerevisiae | Ursic K, Ogrizovic M, ..., Petrovic U | 10.1186/s12866-017-1088-1 |
| 25505024 | Functional importance of Psi38 and Psi39 in distinct tRNAs, amplified fortRNAGln(UUG) by unexpected temperature sensitivity of the s2U modification inyeast | Han L, Kon Y, Phizicky EM | 10.1261/rna.048173.114 |
| 25747122 | Loss of anticodon wobble uridine modifications affects tRNA(Lys) function andprotein levels in Saccharomyces cerevisiae | Klassen R, Grunewald P, ..., Schaffrath R | 10.1371/journal.pone.0119261 |
| 25747390 | Urmylation and tRNA thiolation functions of ubiquitin-like Uba4.Urm1 systems areconserved from yeast to man | Judes A, Ebert F, ..., Schaffrath R | 10.1016/j.febslet.2015.02.024 |
| 32901956 | Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNAthiolation and ubiquitin-like conjugation | Pabis M, Termathe M, ..., Glatt S | 10.15252/embj.2020105087 |
| 28357324 | Sulfur transfer and activation by ubiquitin-like modifier system Uba4*Urm1 linkprotein urmylation and tRNA thiolation in yeast | Judes A, Bruch A, ..., Schaffrath R | 10.15698/mic2016.11.539 |
| 22177309 | Lactic-acid stress causes vacuolar fragmentation and impairs intracellularamino-acid homeostasis in Saccharomyces cerevisiae | Suzuki T, Sugiyama M, ..., Harashima S | 10.1016/j.jbiosc.2011.11.010 |
| 20479142 | Allele-specific suppressors of lin-1(R175Opal) identify functions of MOC-3 andDPH-3 in tRNA modification complexes in Caenorhabditis elegans | Kim S, Johnson W, ..., Han M | 10.1534/genetics.110.118406 |