Detailed view for PF3D7_1012400

Basic information

TDR Targets ID: 1197
Plasmodium falciparum, hypoxanthine-guanine phosphoribosyltransferase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 7.6565 | Length (AA): 231 | MW (Da): 26362 | 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

PF00156   Phosphoribosyl transferase domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005737   cytoplasm  
GO:0004422   hypoxanthine phosphoribosyltransferase activity  
GO:0009116   nucleoside metabolic process  
GO:0006166   purine ribonucleoside salvage  

Structural information

Modbase 3D models:

There are 2 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
2 229 1cjb (A) 2 229 99.99 0 1 2.31 -2.29
1 228 3ozf (A) 1 228 99.99 0 1 2.25341 -1.74

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:

PDB tag
  • 1CJB:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2VFA:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3OZF:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3OZG:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, gametocyte, merozoite, sporozoite, early ring, early schizont, early trophozoite, late ring, late schizont, late trophozoite, Oocyst, Ring, Female Gametocyte. Otto TD PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Male Gametocyte. Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Sporozoite. Zanghi G
Show/Hide expression data references
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.
  • 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.
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.

Orthologs

Ortholog group members (OG5_127374)

Species Accession Gene Product
Arabidopsis thaliana AT1G71750   hypoxanthine phosphoribosyltransferase
Brugia malayi Bm1_19890   Phosphoribosyl transferase domain containing protein
Caenorhabditis elegans CELE_Y105E8B.5   Protein Y105E8B.5
Dictyostelium discoideum DDB_G0285193   hypoxanthine phosphoribosyltransferase
Escherichia coli b0125   hypoxanthine phosphoribosyltransferase
Echinococcus granulosus EgrG_000758800   hypoxanthine guanine phosphoribosyltransferase
Echinococcus granulosus EgrG_000758900   hypoxanthine guanine phosphoribosyltransferase
Echinococcus multilocularis EmuJ_000758900   hypoxanthine guanine phosphoribosyltransferase
Echinococcus multilocularis EmuJ_000758800   hypoxanthine guanine phosphoribosyltransferase
Giardia lamblia GL50803_6436   Guanine phosphoribosyltransferase
Homo sapiens ENSG00000099256   phosphoribosyl transferase domain containing 1
Homo sapiens ENSG00000165704   hypoxanthine phosphoribosyltransferase 1
Leishmania braziliensis LbrM.21.0990   hypoxanthine-guanine phosphoribosyltransferase
Leishmania braziliensis LbrM.21.1000   xanthine phosphoribosyltransferase
Leishmania donovani LdBPK_210990.1   xanthine phosphoribosyltransferase
Leishmania donovani LdBPK_210980.1   hypoxanthine-guanine phosphoribosyltransferase
Leishmania infantum LinJ.21.0990   xanthine phosphoribosyltransferase
Leishmania infantum LinJ.21.0980   hypoxanthine-guanine phosphoribosyltransferase
Leishmania major LmjF.21.0845   hypoxanthine-guanine phosphoribosyltransferase
Leishmania major LmjF.21.0850   xanthine phosphoribosyltransferase
Leishmania mexicana LmxM.21.0850   xanthine phosphoribosyltransferase
Leishmania mexicana LmxM.21.0845   hypoxanthine-guanine phosphoribosyltransferase
Mycobacterium leprae ML0214   Probable hypoxanthine-guanine phosphoribosyltransferase Hpt (HGPRT) (HGPRTase) (hypoxanthine phosphoribosyltransferase) (IMP pho
Mus musculus ENSMUSG00000025630   hypoxanthine guanine phosphoribosyl transferase
Mycobacterium tuberculosis Rv3624c   Hypoxanthine-guanine phosphoribosyltransferase Hpt (HGPRT) (HGPRTase) (hypoxanthine phosphoribosyltransferase) (imp pyrophosphor
Mycobacterium ulcerans MUL_4200   hypoxanthine-guanine phosphoribosyltransferase Hpt
Neospora caninum NCLIV_038170   Hypoxanthine phosphoribosyltransferase (EC 2.4.2.8), related
Onchocerca volvulus OVOC11850  
Plasmodium berghei PBANKA_1210800   hypoxanthine-guanine phosphoribosyltransferase, putative
Plasmodium falciparum PF3D7_1012400   hypoxanthine-guanine phosphoribosyltransferase
Plasmodium knowlesi PKNH_0812200   hypoxanthine-guanine phosphoribosyltransferase, putative
Plasmodium vivax PVX_094840   hypoxanthine-guanine phosphoribosyltransferase, putative
Schistosoma japonicum Sjp_0023450   Hypoxanthine-guanine phosphoribosyltransferase, putative
Schistosoma japonicum Sjp_0023460   ko:K00760 hypoxanthine phosphoribosyltransferase [EC2.4.2.8], putative
Schistosoma mansoni Smp_168500   hypoxanthine-guanine phosphoribosyltransferase
Schistosoma mansoni Smp_103560   hypoxanthine-guanine phosphoribosyltransferase
Schmidtea mediterranea mk4.002646.06  
Schmidtea mediterranea mk4.000023.23  
Schmidtea mediterranea mk4.005084.05  
Schmidtea mediterranea mk4.016658.00  
Schmidtea mediterranea mk4.016685.01  
Schmidtea mediterranea mk4.013413.00  
Schmidtea mediterranea mk4.001970.04  
Schmidtea mediterranea mk4.010510.00  
Trypanosoma brucei gambiense Tbg972.10.1690   hypoxanthine-guanine phosphoribosyltransferase, putative
Trypanosoma brucei gambiense Tbg972.10.1600   hypoxanthine-guanine phosphoribosyltransferase, putative
Trypanosoma brucei gambiense Tbg972.10.1590   hypoxanthine-guanine phosphoribosyltransferase, putative
Trypanosoma brucei Tb927.10.1400   hypoxanthine-guanine phosphoribosyltransferase
Trypanosoma brucei Tb927.10.1470   hypoxanthine-guanine phosphoribosyltransferase
Trypanosoma brucei Tb927.10.1390   hypoxanthine-guanine phosphoribosyltransferase, putative
Trypanosoma congolense TcIL3000_10_1180   hypoxanthine-guanine phosphoribosyltransferase, putative
Trypanosoma congolense TcIL3000_10_1280   hypoxanthine-guanine phosphoribosyltransferase
Trypanosoma congolense TcIL3000_10_1170   hypoxanthine-guanine phosphoribosyltransferase, putative
Trypanosoma cruzi TcCLB.509693.80   hypoxanthine-guanine phosphoribosyltransferase, putative
Trypanosoma cruzi TcCLB.506457.40   hypoxanthine-guanine phosphoribosyltransferase, putative
Trypanosoma cruzi TcCLB.509693.70   hypoxanthine-guanine phosphoribosyltransferase, putative
Trypanosoma cruzi TcCLB.506457.30   hypoxanthine-guanine phosphoribosyltransferase, putative
Toxoplasma gondii TGME49_200320   hypoxanthine-xanthine-guanine phosphoribosyl transferase HXGPRT
Trichomonas vaginalis TVAG_243770   hypoxanthine-guanine phosphoribosyltransferase, putative

Essentiality

PF3D7_1012400 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.1390 Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.1390 Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.1390 Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb927.10.1390 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
Tb927.10.1400 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.10.1400 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.1400 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.10.1400 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
b0125 Escherichia coli non-essential goodall
PBANKA_1210800 Plasmodium berghei Slow plasmo
Show/Hide essentiality data references
  • 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.
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • 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.
  • 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) decreased time (PATO:0000716) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) inferred from anti-sense experiment (ECO:0000018) Plasmodium falciparum No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 8366890
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium falciparum No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: Drug: deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol 5-phosphate (immucillinHP) and (1S)-1-(9-deazaguanin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol 5-phosphate (immucillinGP). . References: 10360365 3574349

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

Druggability index (range: 0 to 1): 0.8

Known modulators for this target

Compound Source Reference
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Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Homo sapiens hypoxanthine phosphoribosyltransferase 1 Compounds References
Schistosoma mansoni hypoxanthine-guanine phosphoribosyltransferase Compounds References
Trypanosoma cruzi hypoxanthine-guanine phosphoribosyltransferase, putative Compounds References
Trypanosoma cruzi hypoxanthine-guanine phosphoribosyltransferase, putative Compounds References
Trypanosoma brucei hypoxanthine-guanine phosphoribosyltransferase Compounds References
Trypanosoma brucei hypoxanthine-guanine phosphoribosyltransferase Compounds References
Trypanosoma cruzi hypoxanthine-guanine phosphoribosyltransferase, putative Compounds References
Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase, putative Compounds References
Trypanosoma cruzi hypoxanthine-guanine phosphoribosyltransferase, putative Compounds References
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.1913 1 1
0.0111 1 1
0.0387 1 0.5
0.0197 0.3705 1
0.02 0.5956 1
0.02 0.5214 1
0.0185 0.3855 1
0.0191 0.3619 1
0.0111 1 0.5
0.0111 0.3624 0.5
0.0199 1 0.5
0.1093 1 1
0.0111 0.3115 1
0.1563 1 1
0.2019 0.4241 0.4241
0.0288 0.2516 1
0.0181 1 1
0.0198 1 0.5
0.0111 0.2635 1
0.0332 1 0.5
0.2019 0.4241 0.4241
0.0213 0.2938 0.5
0.0111 0.3115 1
0.0221 1 0.5
0.094 1 1
0.0582 0.4787 1
0.0181 1 1
0.0185 0.3855 1
0.0111 1 0.5
0.0178 1 1
0.0199 1 1
0.0221 1 0.5
0.019 0.3681 1
0.0483 0.6135 0.5
0.0462 1 1
0.0199 1 0.5
0.047 1 1
0.1921 1 1
0.2386 1 1
0.0185 1 1
0.1811 1 1
0.0937 1 1
0.0178 0.3649 1
0.0188 0.3593 1
0.0193 0.9045 1
0.0197 1 0.5
0.0111 0.3624 0.5
0.0192 1 1
0.0291 0.3143 1
0.0111 1 0.5
0.0288 0.2516 1
0.0275 0.3938 1
0.0091 1 1
0.009 1 0.5
0.2386 1 1
0.0295 0.2986 1
0.0179 1 0.5
0.0221 1 0.5
0.009 1 1
0.0196 1 0.5
0.0209 1 0.5
0.021 1 0.5
0.0314 1 0.5
0.0189 0.8616 1
0.0092 0.8505 0.8505
0.0189 0.4774 0.5
0.0195 1 1
0.1039 1 1
0.0198 1 0.5
0.0582 1 1
0.0193 0.9045 1
0.0182 1 0.5
0.1337 1 1
0.0189 0.3924 1
0.2024 1 1
0.0559 0.6319 1
0.0389 0.8303 1
0.0111 1 0.5
0.0194 0.7112 1
0.0488 1 1
0.0091 0.407 0.5
0.0187 0.3297 0.5
0.0193 0.3857 1
0.0094 0.5553 0.5619
0.0111 1 1
0.1039 1 1
0.1416 1 1
0.0091 1 1
0.0577 1 0.5
0.0181 1 1
0.0332 1 0.5
0.0187 0.3297 0.5
0.0091 1 1
0.0192 0.4117 1
0.009 1 0.5
0.0181 0.3509 1
0.0332 1 0.5
0.0196 1 0.5
0.019 0.666 1
0.1421 1 1
0.1936 1 1
0.0197 0.3389 0.5
0.019 0.3648 1
0.02 0.5214 1
0.0185 0.3855 1
0.0187 0.9401 1
0.0443 1 1
0.2019 0.4241 0.4241
0.0194 0.6978 1
0.0206 0.2852 0.3815
0.0272 1 0.5
0.0291 0.3143 1
0.009 0.3034 0.5619
0.1493 1 1
0.0845 1 1
0.0092 0.5553 0.5619
0.0185 0.3691 1
0.0202 1 0.5
0.0582 0.4787 1
0.0189 1 0.5
0.021 0.565 1
0.0221 1 0.5
0.0193 0.9408 1
0.0203 0.3651 0.5
0.0182 0.5043 1
0.0443 0.4881 0.5
0.019 0.4868 1
0.0185 0.3855 1
0.0196 1 1
0.1625 1 1
0.0196 1 0.5
0.1521 1 1
0.1413 1 1
0.037 0.6382 1
0.0111 1 1
0.1737 1 1
0.0332 1 0.5
0.0377 1 1
0.0189 0.3635 1
0.0193 1 0.5
0.02 0.5956 1
0.0197 1 0.5
0.0191 0.3297 0.5
0.0192 1 0.5
0.0111 1 0.5
0.036 1 1
0.0297 1 0.5
0.1728 1 1
0.0655 1 1
0.0096 1 0.5
0.0332 1 0.5
0.02 0.54 1
0.0197 1 1
0.0576 0.5826 1
0.0675 1 1
0.0483 0.6135 0.5
0.0651 1 1
0.0189 0.3924 1
0.0111 0.3624 0.5
0.0187 1 0.5
0.0091 1 1
0.1509 1 1
0.0093 0.5553 0.5619
0.0091 0.407 0.5
0.0559 0.6319 1
0.0189 0.3924 1
0.0272 1 0.5
0.1521 1 1
0.02 0.5214 1
0.0387 1 1
0.0194 1 0.5
0.019 0.3699 1
0.0777 1 1
0.1512 1 1
0.0192 1 0.5
0.0229 0.378 1
0.0576 1 1
0.0196 1 0.5
0.0089 0.5564 0.5619
0.0297 1 0.5
0.0188 1 0.5
0.0576 1 1
0.0206 0.77 1
0.019 0.3681 1
0.0193 0.9045 1
0.0193 1 0.5
0.0091 1 1
0.0582 0.4787 1
0.0197 1 0.5
0.0192 1 0.5
0.0111 0.7794 1
0.036 1 1
0.2523 1 1
0.02 0.5214 1
0.1733 1 1
0.0483 0.6135 0.5
0.0111 1 0.5
0.1421 0.9481 1
0.02 0.54 1
0.2386 1 1
0.0289 0.5814 1

Assayability

Assay information

  • Assay for Hypoxanthine-Guanine (2.4.2.8 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • Growth Inhibition Assay BINDINGDB
  • Growth Inhibition Assay. The [3H]-hypoxanthine growth inhibition assay (Desjardins et al., 1979 Antimicrobial Agents Chemother 16. 710-718) was used to evaluate the in vitro antimalarial activity of the compounds. Briefly, synchronised parasite cultures (>90% rings, 6 to 8 h post invasion) in [3H]-RPMI-LPLF complete medium with 1% parasitaemia and 2% haematocrit were exposed to the compounds at ten two-fold concentrations. Chloroquine was used as a reference drug. Uninfected RBCs at 2% haematocrit were used as background controls. Two drug exposure periods were evaluated (48 h and 96 h). For the 48 h exposure period, the plates were incubated in the gas mixture at 37° C. for approximately 20 h (about 24 h post-invasion). To each well, 0.2 uCi of tritiated hypoxanthine (GE Healthcare, Amersham) solution in [3H]RPMI-1640-LPLF was added. The plates were incubated for a further 24 h at 37° C. in the gas Mixture and then frozen at â¿¿20° C. For the 96 h exposure period, the plates were incubated
  • Spectrophotometric Assay BINDINGDB
  • Spectrophotometric Assay. The Ki values were determined using a spectrophotometric assay at 25° C., 0.1 M Tris-HCl, 10 mM MgCl2, pH 7.4 (Keough, D. T.; Ng, A. L.; Winzor, D. J.; Emmerson, B. T.; de Jersey, J. Purification and characterization of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase and comparison with the human enzyme. Mol. Biochem. Parasitol. 1999, 98, 29-41; Plasmodium vivaxhypoxanthine-guanine phosphoribosyltransferase. a target for anti-malarial chemotherapy. Kerough, D. T. Hockova. D, Krecmerova, M., Naesens, L., Brereton, I. M., de Jersey, J and Guddat, L, W, Mol. Biochem. Parasitol (2010) 173. 165-169). The Ki values are Ki(app) as they were measured at a single concentration of the second substrate. The concentration of the second substrate (guanine) was saturating. 60 ¿M
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falsiparum ( 1 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    PF3D7_1012400 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Plasmodium lophurae ( 1 )

Bibliographic References

32 literature references were collected for this gene.

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Gene identifier PF3D7_1012400 (Plasmodium falciparum), hypoxanthine-guanine phosphoribosyltransferase
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