Detailed view for PF3D7_1246100

Basic information

TDR Targets ID: 5496
Plasmodium falciparum, delta-aminolevulinic acid synthetase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.6311 | Length (AA): 630 | MW (Da): 73547 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 0

Druggability Group : DG3

Targets have been classified into druggability groups (DG) according to their druggability score in network driven prioritizations. DGs range from 1 to 5; the higher the group number, the higher the chance of the target to be druggable

Pfam domains

PF00155   Aminotransferase class I and II

Gene Ontology

Mouse over links to read term descriptions.
GO:0005739   mitochondrion  
GO:0030170   pyridoxal phosphate binding  
GO:0016740   transferase activity  
GO:0003870   5-aminolevulinate synthase activity  
GO:0003824   catalytic activity  
GO:0033014   tetrapyrrole biosynthetic process  
GO:0009058   biosynthetic process  
GO:0008152   metabolic process  

Structural information

Modbase 3D models:

There are 10 models calculated for this protein. More info on these models, including the models themselves is available at: Modbase

Target Beg Target End Template Template Beg Template End Identity Evalue Model Score MPQS zDope
188 614 1js3 (A) 4 474 10.00 0 1 0.63 -0.56
218 616 1fc4 (A) 2 396 29.00 0 1 1.15 -1.49
220 611 2bwn (A) 2 397 36.00 0 1 1.12 -1.62
4 176 4uos (A) 6 178 16.00 0.28 0.03 0.461103 -0.79
20 216 4u0r (A) 209 432 31.00 0.36 0.38 0.200098 1.41
215 616 1fc4 (A) 0 396 29.00 0 1 1.0608 -0.61
221 616 3tqx (A) 1 395 31.00 0 1 1.03127 -0.31
227 608 2bwn (A) 15 394 33.00 0 1 1.04405 -0.46
234 613 3a2b (A) 21 392 29.00 0 1 1.03387 -0.79
257 579 4iw7 (A) 26 335 27.00 0 1 0.780098 0.03

Help me make sense of these data.

Target Beg: first modeled residue
Target End: last modeled residue
Template: template structure used for modelling (PDB accession and chain)
Template Beg: first template residue in target-template alignment
Template End: last template residue in target-template alignment
Identity: sequence identity
Evalue: E value for target-template hit
Model Score: GA341 score (>0.7 for reliable model)
MPQS: ModPipe Quality Score (>1.1 for reliable model)
zDope: zDope Score (negative for reliable model)

A more detailed description of these scores is available at the Modbase Model Evaluation Help Pages, and in the papers referenced therein.

PDB Structures:

No structure availble in the PDB for this protein

Expression

Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile gametocyte, Oocyst. PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile early trophozoite, late trophozoite, Female Gametocyte. PlasmoDB Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, Ring, Sporozoite, Male Gametocyte. Otto TD Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs. Otto TD
Show/Hide expression data references
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.

Orthologs

Ortholog group members (OG5_126783)

Species Accession Gene Product
Arabidopsis thaliana AT5G04620   7-keto-8-aminopelargonic acid (KAPA) synthase
Brugia malayi Bm1_01535   2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial precursor
Candida albicans CaO19.2601   similar to S. cerevisiae HEM1 (YDR232W) mitochondrial 5-aminolevulinic acid synthase involved in heme biosynthesis
Candida albicans CaO19.10132   similar to S. cerevisiae HEM1 (YDR232W) mitochondrial 5-aminolevulinic acid synthase involved in heme biosynthesis
Caenorhabditis elegans CELE_T25B9.1   Protein T25B9.1
Dictyostelium discoideum DDB_G0280763   5-aminolevulinate synthase
Drosophila melanogaster Dmel_CG3017   Aminolevulinate synthase
Drosophila melanogaster Dmel_CG10361   CG10361 gene product from transcript CG10361-RA
Escherichia coli b0776   8-amino-7-oxononanoate synthase
Escherichia coli b3617   glycine C-acetyltransferase
Echinococcus granulosus EgrG_000107200   2 amino 3 ketobutyrate coenzyme A ligase
Echinococcus granulosus EgrG_000574600   5 aminolevulinate synthase
Echinococcus granulosus EgrG_000575200   5 aminolevulinate synthase
Echinococcus multilocularis EmuJ_000107200   2 amino 3 ketobutyrate coenzyme A ligase
Echinococcus multilocularis EmuJ_000574600   5 aminolevulinate synthase
Echinococcus multilocularis EmuJ_000575200   5 aminolevulinate synthase
Homo sapiens ENSG00000158578   5'-aminolevulinate synthase 2
Homo sapiens ENSG00000023330   5'-aminolevulinate synthase 1
Homo sapiens ENSG00000100116   glycine C-acetyltransferase
Loa Loa (eye worm) LOAG_04085   2-amino-3-ketobutyrate coenzyme A ligase
Mycobacterium leprae ML1217   PROBABLE 8-AMINO-7-OXONONANOATE SYNTHASE BIOF (AONS) (8-AMINO-7-KETOPELARGONATE SYNTHASE) (7-KETO-8-AMINO-PELARGONIC ACID SYNTHE
Mus musculus ENSMUSG00000006378   glycine C-acetyltransferase (2-amino-3-ketobutyrate-coenzyme A ligase)
Mus musculus ENSMUSG00000025270   aminolevulinic acid synthase 2, erythroid
Mus musculus ENSMUSG00000032786   aminolevulinic acid synthase 1
Mycobacterium tuberculosis Rv1569   Probable 8-amino-7-oxononanoate synthase BioF1 (AONS) (8-amino-7-ketopelargonate synthase) (7-keto-8-amino-pelargonic acid synth
Mycobacterium tuberculosis Rv0032   Possible 8-amino-7-oxononanoate synthase BioF2 (AONS) (8-amino-7-ketopelargonate synthase) (7-keto-8-amino-pelargonic acid synth
Mycobacterium ulcerans MUL_4045   8-amino-7-oxononanoate synthase
Mycobacterium ulcerans MUL_1560   8-amino-7-oxononanoate synthase
Mycobacterium ulcerans MUL_0241   8-amino-7-oxononanoate synthase
Mycobacterium ulcerans MUL_1966   8-amino-7-oxononanoate synthase
Mycobacterium ulcerans MUL_2843   8-amino-7-oxononanoate synthase
Neospora caninum NCLIV_027820   5-aminolevulinic acid synthase, related
Oryza sativa 4349380   Os10g0560900
Oryza sativa 4327870   Os01g0736400
Plasmodium berghei PBANKA_1459200   delta-aminolevulinic acid synthetase
Plasmodium falciparum PF3D7_1246100   delta-aminolevulinic acid synthetase
Plasmodium knowlesi PKNH_1465700   delta-aminolevulinic acid synthetase, putative
Plasmodium vivax PVX_101195   delta-aminolevulinic acid synthetase, putative
Plasmodium yoelii PY05459   delta-aminolevulinic acid synthetase
Saccharomyces cerevisiae YDR232W   5-aminolevulinate synthase
Schistosoma japonicum Sjp_0209020   ko:K00643 5-aminolevulinate synthase [EC2.3.1.37], putative
Schistosoma mansoni Smp_045260   5-aminolevulinic acid synthase
Schmidtea mediterranea mk4.000755.02   2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial
Schmidtea mediterranea mk4.052690.00   2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial
Schmidtea mediterranea mk4.042742.00   2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial
Schmidtea mediterranea mk4.042742.01   2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial
Schmidtea mediterranea mk4.000655.01   5-aminolevulinate synthase, nonspecific, mitochondrial
Trypanosoma brucei gambiense Tbg972.8.6090   2-amino-3-ketobutyrate coenzyme A ligase, putative,glycine acetyltransferase, putative
Trypanosoma brucei Tb927.8.6060   glycine acetyltransferase, putative
Trypanosoma congolense TcIL3000_8_5850   glycine acetyltransferase, putative
Trypanosoma cruzi TcCLB.511899.40   2-amino-3-ketobutyrate coenzyme A ligase, putative
Trypanosoma cruzi TcCLB.511899.10   2-amino-3-ketobutyrate coenzyme A ligase, putative
Trypanosoma cruzi TcCLB.511071.140   2-amino-3-ketobutyrate coenzyme A ligase, putative
Toxoplasma gondii TGME49_258690   5-aminolevulinic acid synthase domain-containing protein
Wolbachia endosymbiont of Brugia malayi Wbm0133   5-aminolevulinate synthase

Essentiality

PF3D7_1246100 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
mtu1597 Mycobacterium tuberculosis non-essential nmpdr
mtu32 Mycobacterium tuberculosis non-essential nmpdr
Tb927.8.6060 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.6060 Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.6060 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.6060 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
b0776 Escherichia coli non-essential goodall
b3617 Escherichia coli non-essential goodall
YDR232W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1459200 Plasmodium berghei Dispensable plasmo
TGME49_258690 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • goodall The Essential Genome of Escherichia coli K-12 (Transposon directed high-throughput mutagenesis) Goodall, Emily CA, et al. "The essential genome of Escherichia coli K-12." mBio 9.1 (2018): e02096-17.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • sidik A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes. Sidik, Saima M., et al. "A genome-wide CRISPR screen in toxoplasma identifies essential apicomplexan genes." Cell 166.6 (2016): 1423-1435.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • plasmo Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes. Bushell, Ellen, et al. "Functional profiling of a Plasmodium genome reveals an abundance of essential genes." Cell 170.2 (2017): 260-272.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) in vivo inhibition (TDR:00016) Plasmodium falciparum 173163   543925  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 12119044
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium falciparum 173163   543925  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 12119044

In TDR Targets, information about phenotypes that are caused by drugs, or by genetic manipulation of cells (e.g. gene knockouts or knockdowns) is manually curated from the literature. These descriptions help to describe the potential of the target for drug development. If no information is available for this gene or if the information is incomplete, this may mean that i) the papers containing this information either appeared after the curation effort for this organism was carried out or they were inadvertently missed by curators; or that ii) the curation effort for this organism has not yet started.

In any case, if you have information about papers containing relevant validation data for this target, please contact us.

Annotated validation

No validation data for this target

Associated compounds / Druggability

Known modulators for this target

Compound Source Reference
Curated by TDRTargets References
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Non orthologous druggable targets
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model
No druggable targets predicted through repurposing network model

Assayability

Assay information

  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falciparum ( 1 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    PF3D7_1246100 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Plasmodium falciparum ( 1 )

Bibliographic References

8 literature references were collected for this gene.

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Gene identifier PF3D7_1246100 (Plasmodium falciparum), delta-aminolevulinic acid synthetase
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