Detailed view for TcCLB.509167.20

Basic information

TDR Targets ID: 33497
Trypanosoma cruzi, 3-hydroxy-3-methylglutaryl-CoA reductase, putative

Source Database / ID:  TriTrypDB  GeneDB

pI: 8.7213 | Length (AA): 452 | MW (Da): 48011 | Paralog Number: 1

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 1

Druggability Group : DG4

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

PF00368   Hydroxymethylglutaryl-coenzyme A reductase

Gene Ontology

Mouse over links to read term descriptions.
GO:0016616   oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor  
GO:0004420   hydroxymethylglutaryl-CoA reductase (NADPH) activity  
GO:0016021   integral to membrane  
GO:0050662   coenzyme binding  
GO:0050661   NADP binding  
GO:0055114   oxidation reduction  
GO:0015936   coenzyme A metabolic process  
GO:0008299   isoprenoid biosynthetic process  

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
37 448 1dqa (A) 462 870 52.00 0 1 1.59 -0.97
23 438 3ccz (A) 448 860 51.00 0 1 1.52065 -0.29

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 80-100% percentile epimastigote, metacyclic. Smircich P
Show/Hide expression data references
  • Smircich P Ribosome profiling reveals translation control as a key mechanism generating differential gene expression in Trypanosoma cruzi.

Orthologs

Ortholog group members (OG5_127955)

Species Accession Gene Product
Arabidopsis thaliana AT1G76490   3-hydroxy-3-methylglutaryl-coenzyme A reductase 1
Arabidopsis thaliana AT2G17370   3-hydroxy-3-methylglutaryl-coenzyme A reductase 2
Brugia malayi Bm1_54020   Hydroxymethylglutaryl-coenzyme A reductase family protein
Candida albicans CaO19.1031   hydroxymethylglutaryl-CoA reductase (ergosterol biosynthesis)
Candida albicans CaO19.8633   hydroxymethylglutaryl-CoA reductase (ergosterol biosynthesis)
Caenorhabditis elegans CELE_F08F8.2   Protein HMGR-1
Dictyostelium discoideum DDB_G0276615   hmg CoA reductase B
Dictyostelium discoideum DDB_G0269142   hmg CoA reductase A
Drosophila melanogaster Dmel_CG10367   HMG Coenzyme A reductase
Echinococcus granulosus EgrG_000630800   hydroxymethylglutaryl coenzyme A reductase
Echinococcus multilocularis EmuJ_000630800   hydroxymethylglutaryl coenzyme A reductase
Homo sapiens ENSG00000113161   3-hydroxy-3-methylglutaryl-CoA reductase
Leishmania braziliensis LbrM.30.3180   3-hydroxy-3-methylglutaryl-CoA reductase, putative
Leishmania donovani LdBPK_303230.1   3-hydroxy-3-methylglutaryl-CoA reductase, putative
Leishmania infantum LinJ.30.3230   3-hydroxy-3-methylglutaryl-CoA reductase, putative
Leishmania major LmjF.30.3190   3-hydroxy-3-methylglutaryl-CoA reductase
Leishmania mexicana LmxM.29.3190   3-hydroxy-3-methylglutaryl-CoA reductase, putative
Loa Loa (eye worm) LOAG_01960   hypothetical protein
Mus musculus ENSMUSG00000021670   3-hydroxy-3-methylglutaryl-Coenzyme A reductase
Mycobacterium ulcerans MUL_3522   hydroxymethylglutaryl-coenzyme a (HMG-CoA) reductase
Oryza sativa 4347443   Os09g0492700
Oryza sativa 9272427   Os02g0713900
Oryza sativa 4346017   Os08g0512700
Saccharomyces cerevisiae YML075C   hydroxymethylglutaryl-CoA reductase (NADPH) HMG1
Saccharomyces cerevisiae YLR450W   hydroxymethylglutaryl-CoA reductase (NADPH) HMG2
Schistosoma japonicum Sjp_0210190   ko:K00021 3-hydroxy-3-methylglutaryl-CoA reductase [EC1.1.1.34], putative
Schistosoma mansoni Smp_138590   hydroxymethylglutaryl-CoA reductase (NADPH)
Schmidtea mediterranea mk4.000523.07   3-hydroxy-3-methylglutaryl-coenzyme A reductase
Schmidtea mediterranea mk4.000523.08   3-hydroxy-3-methylglutaryl-coenzyme A reductase
Trypanosoma brucei gambiense Tbg972.6.4330   3-hydroxy-3-methylglutaryl-CoA reductase, putative
Trypanosoma brucei Tb927.6.4540   3-hydroxy-3-methylglutaryl-CoA reductase, putative
Trypanosoma congolense TcIL3000_6_3990   3-hydroxy-3-methylglutaryl-CoA reductase, putative
Trypanosoma cruzi TcCLB.506831.40   3-hydroxy-3-methylglutaryl-CoA reductase
Trypanosoma cruzi TcCLB.509167.20   3-hydroxy-3-methylglutaryl-CoA reductase, putative

Essentiality

TcCLB.509167.20 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.6.4540 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.6.4540 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.6.4540 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.6.4540 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F08F8.2 Caenorhabditis elegans embryonic lethal wormbase
CELE_F08F8.2 Caenorhabditis elegans larval arrest wormbase
CELE_F08F8.2 Caenorhabditis elegans slow growth wormbase
CELE_F08F8.2 Caenorhabditis elegans sterile wormbase
Show/Hide essentiality data references
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • 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

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) decreased (PATO:0000468) epimastigote (BTO:0000409) inferred from in vitro culture assay (ECO:0000182) Trypanosoma cruzi 9366   213003   581126  
Annotator: millerja@u.washington.edu. Comment: . References: 8460926

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
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Rattus norvegicus HMG-CoA reductase Compounds References
Schistosoma mansoni hydroxymethylglutaryl-CoA reductase (NADPH) Compounds References
Sus scrofa 3-hydroxy-3-methylglutaryl-coenzyme A reductase Compounds References
Mesocricetus auratus 3-hydroxy-3-methylglutaryl-coenzyme A reductase Compounds References
Homo sapiens 3-hydroxy-3-methylglutaryl-CoA reductase Compounds References
Trypanosoma cruzi 3-hydroxy-3-methylglutaryl-CoA reductase Compounds References
Mus musculus 3-hydroxy-3-methylglutaryl-Coenzyme A reductase 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
0.0165 0.6494 0.5
0.4227 0.7437 1
0.0467 0.4524 0.5
3.5272 1 1
0.0165 1 1
0.3081 1 1
0.0826 1 1
0.2604 0.2872 1
0.0127 0.3415 1
0.1195 0.3064 1
0.0302 1 0.5
0.1546 1 0.5
0.2618 1 0.5
0.1112 0.3621 0.3621
0.4096 0.8014 1
0.0918 1 1
0.2982 1 1
0.11 0.5161 1
0.033 0.7283 1
0.2827 0.3371 1
0.4658 1 0.5
0.0162 0.9621 1
0.0165 0.6408 1
0.0165 0.9417 0.5
0.069 0.3075 1
0.251 1 1
0.033 0.8585 0.5
0.0165 1 0.5
0.1023 1 0.5
0.1002 1 1
0.0165 0.3082 0.3082
0.0406 0.4752 1
0.2245 1 1
0.5673 1 0.5
0.3169 0.8784 1
1.5128 0.3443 1
0.033 1 0.5
0.3267 1 0.5
0.4619 1 1
0.8397 0.4527 1
0.11 0.7329 1
0.1271 0.3699 1
0.0165 1 1
0.016 0.2996 0.466
0.3894 1 1
0.1365 0.5 0.5
0.4401 1 1
0.0134 0.8813 0.5
0.0165 0.5436 0.5
0.0976 1 1
0.0741 1 0.5
0.016 0.5505 0.5535
0.0165 0.4137 0.5
0.2628 1 0.5
0.1721 1 1
0.3203 1 1
0.0815 0.3125 1
0.331 0.8849 1
1.1314 1 1
0.2639 1 1
0.0298 1 0.5
0.1101 0.4278 1
0.0138 0.3889 0.5784
0.0165 1 0.5
0.2531 1 0.5
0.4604 1 1
1.2667 1 1
0.033 1 0.5
0.2604 0.2872 1
0.0695 0.5397 1
0.1326 1 1
0.4838 1 0.5
0.0668 1 1
0.0165 0.498 0.5
0.0757 0.2675 0.328
0.2827 0.3371 1
0.0312 0.7535 0.8454
0.1419 0.3505 1
0.1136 0.5457 1
0.0165 0.3866 1
0.0615 0.438 1
0.0165 1 0.5
0.0146 0.3095 1
0.1064 0.401 1
0.0858 1 0.5
0.0266 0.3619 0.8186
0.041 0.3248 1
0.6815 0.695 1
0.4131 1 1
0.0463 1 1
0.1027 1 0.5
0.031 0.3075 1
0.138 1 1
0.223 1 0.5
0.0325 0.5606 1
0.5442 1 1
0.2827 0.3371 1
0.2806 1 0.5
0.1356 0.5768 1
0.1205 1 1
0.0165 0.2898 1
0.2966 1 0.5
0.0271 0.3779 0.5
0.0165 1 0.5
0.3998 1 1
0.3739 1 0.5
0.0414 0.3577 1
0.029 0.2634 1
0.1237 0.3827 1
0.0737 0.4514 1
0.0977 1 0.5
0.6669 1 1
0.0408 0.3311 1
0.1493 1 0.5
0.6622 1 0.5
0.5514 1 0.5
3.0415 0.8227 1
1.1314 1 1
0.3298 0.3524 1
0.1419 0.8687 1
0.1497 0.307 0.6568
0.0585 0.5427 1
1.1314 1 1
0.6627 1 0.5
0.1803 1 0.5
0.1051 1 0.5
0.0533 1 0.5
0.0165 1 0.5
0.0415 0.502 1
0.0238 0.5393 1
0.226 1 1
0.0312 0.3579 0.5
0.3535 1 1
0.1628 1 0.5
0.223 1 0.5
0.0845 0.7574 1
0.0165 0.39 1
0.1341 1 0.5
0.0727 0.652 1
0.0313 0.4493 1
0.2283 0.6385 0.895
0.033 1 0.5
0.1015 1 1
0.099 1 1
0.0681 0.4253 1
0.4271 1 0.5
0.0165 0.3866 1
0.3827 1 0.5
0.0313 0.4493 1
0.0165 1 1
0.3746 0.4068 1
0.2372 1 1
0.0683 0.6766 1
0.0681 0.4202 1
0.0165 0.3647 0.5
0.0133 1 0.5
0.0615 0.438 1
0.2539 1 0.5
0.0442 0.34 1
0.268 1 0.5
0.0138 0.4762 0.5
0.0265 0.9907 1
0.0402 1 0.5
0.1366 0.3516 1
0.1621 1 1
0.1203 1 1
0.0287 0.5466 1
0.0402 0.6281 0.5
0.0971 1 0.5
0.0835 0.405 1
0.3133 1 1
0.3304 0.3879 1
0.0777 1 0.5
0.3548 1 1
0.0165 1 0.5
0.0585 0.5427 1
0.0133 0.2566 1
0.2138 1 0.5
0.0696 0.6257 1
0.0267 0.3279 1
0.1607 0.3923 1
0.1434 1 0.5
0.0402 1 0.5
0.2096 0.2623 1
0.3304 0.3879 1
0.082 0.5546 1
0.1628 1 0.5
0.3557 1 1
0.6066 1 0.5
0.0887 0.3163 0.8614
0.0633 0.7732 1
0.0165 0.4595 1
0.0165 1 0.5
0.327 1 0.5
0.1632 0.9054 1
0.0949 0.338 0.7349
0.3314 1 0.5
0.1114 0.4195 1
0.0838 1 1
0.35 1 1
0.0468 1 0.5
0.3406 0.7946 0.5
0.0165 0.967 1
0.305 1 1
0.0282 0.3161 1
0.3334 1 0.5
0.1017 0.2838 1
0.5427 1 1
0.1541 0.8404 1
0.0165 0.92 0.5
0.2872 1 0.5
0.3313 1 0.5
0.3391 1 0.5
0.1533 1 1
0.118 1 0.5
0.0136 0.5199 1
0.175 1 0.5
0.1479 1 0.5
0.3687 1 1
0.2281 1 1
0.2395 1 1
0.0837 1 0.5
0.0165 1 0.5
0.0546 1 1
0.2534 1 1
0.4099 1 1
0.374 0.344 1
0.0981 0.256 1
0.2383 1 1
0.0165 0.2818 1
0.2558 1 0.5
0.0136 1 1
0.075 1 0.5
0.0477 0.5676 1
0.4096 0.8014 1
0.0165 1 0.5
0.4094 1 0.5
0.0264 0.3006 0.854
0.2769 1 1
0.3785 1 0.5
0.1248 1 0.5
0.0812 0.2988 1
0.1621 1 1
0.2606 1 0.5
0.0714 1 1
0.4143 1 0.5
0.0133 0.5025 1
0.3599 1 1
0.0165 0.3343 1
0.033 0.8585 0.5
0.0135 0.7121 1
0.5729 1 1
0.1848 0.8496 0.5
0.2604 0.2872 1
1.1314 1 1
0.041 0.3302 1
0.101 0.9073 1
0.1869 1 0.5
0.0457 1 0.5
0.2768 1 1
0.1373 1 1
0.0165 0.2943 0.3451
0.0326 0.387 0.6578
0.1058 0.9292 1
0.0165 0.5038 1
0.6523 0.4241 1
0.9525 1 1
0.033 1 0.5
0.2779 1 1
0.0991 0.5833 1
0.4016 1 0.5
0.3302 0.3693 1
0.2089 0.258 1
0.0267 0.3279 1
0.0411 0.2746 1
0.1487 0.3432 1
0.2366 1 0.5
0.069 0.3075 1
0.0737 0.4514 1
0.136 1 1
0.0436 0.4751 1
0.0165 0.5038 1
1.1314 1 1
0.1017 0.2838 1
0.2609 1 0.5
0.1011 0.9387 1
0.3302 0.3693 1
0.0165 1 0.5
0.4251 1 1
0.0752 0.4383 0.5
0.316 1 0.5
0.033 1 0.5
0.278 0.3265 0.7048
0.0417 0.2996 1
0.064 0.6782 1
0.0165 0.3217 0.7169
0.251 1 1
0.2617 1 0.5
1.1314 1 1
0.6483 1 1
0.0399 1 0.5
0.1835 1 1
0.3068 1 1
0.6087 0.4263 1
0.4354 1 1
0.0165 1 0.5
0.3594 1 1
0.0475 0.495 1
0.1419 0.8687 1
0.032 0.5589 1
0.3107 1 0.5
0.0872 0.8024 1
0.033 1 0.5
0.0133 0.2882 0.6077
0.0137 0.3803 1
0.0165 1 0.5
0.2829 1 0.5
0.1035 0.9083 1
0.4235 0.5712 1
0.0581 0.3139 1
0.0589 0.5981 1
0.0267 0.3279 1
0.2635 1 0.5
0.0266 0.5168 1
0.2366 1 0.5
0.0148 1 0.5
0.0944 1 0.5
0.1081 1 1
0.3442 1 0.5
0.0282 0.2749 1
0.1479 1 1
0.5244 1 1
0.0441 1 0.5
0.1907 1 0.5
0.0844 1 1
0.0773 0.3195 1
0.033 1 0.5
0.0949 1 0.5
0.4005 1 1
0.1248 1 0.5
2.9242 1 1
0.0412 0.4877 1
0.3223 1 1
1.5373 1 1
0.2769 1 1
0.027 0.3157 1
0.11 0.5161 1
0.3169 0.8784 1
0.304 1 1
0.1516 0.5861 1
0.1737 0.6611 1
0.1114 0.4195 1
1.3249 1 1
0.1444 1 1
0.0137 0.3145 0.5
0.2611 1 0.5
0.3341 1 0.5
0.3105 1 0.5
0.033 0.9591 0.5
0.0757 0.2675 0.328
0.4227 0.7437 1
0.0165 0.5076 0.9068
0.1252 1 0.5
0.0165 1 0.5
0.0485 0.2532 0
0.0442 0.34 1
0.0165 1 0.5
0.0165 1 0.5
0.0753 1 0.5
0.101 0.6438 1
0.2604 0.2872 1
0.1136 0.5457 1
0.05 0.5117 0.5112
0.0853 0.2645 1
0.2044 1 0.5
0.4227 0.7437 1
0.0815 0.3133 1
0.1977 1 1
0.1487 0.3432 1
0.3514 1 0.5
0.2664 1 0.5
0.0133 0.4197 0.5913
0.0457 0.6274 1
0.0737 0.4514 1
0.0165 0.2847 0.4371
0.0165 0.4512 0.5
0.1211 1 0.5
0.1106 0.2944 1
0.5144 1 0.5
0.0165 0.9412 0.5
0.0165 0.2537 1
0.3393 1 0.5
0.2961 1 1
0.2629 1 1
0.4059 1 1
0.0165 0.3089 0.4448
0.4623 1 0.5
0.0318 1 1
0.1963 0.3011 1
0.0165 0.549 0.5
0.0165 1 0.5
0.1155 1 0.5
0.0445 0.5308 1
0.3097 1 1
0.2951 0.6949 0.6897
0.0421 0.6488 1
0.4267 1 0.5
0.0956 1 0.5
0.1237 1 1
0.2283 0.6385 0.895
0.5335 1 0.5
0.0676 0.6047 1
0.0162 0.9621 1
0.0165 0.4168 0.5
1.1314 1 1
0.0538 0.435 1
0.1479 1 0.5
0.0549 0.3863 1
0.0165 0.435 1
1.1314 1 1
0.1607 0.3923 1
0.0233 1 1
0.0165 0.6334 1
0.0958 0.3744 0.5
0.4141 1 1
0.352 1 1
1.2859 0.5603 1
0.3406 0.7946 0.5
0.0165 0.39 1
0.0212 0.258 0.7317
0.0713 0.4966 1
0.1428 0.2818 1
0.0278 0.3041 1
0.4474 0.3883 1
0.5442 1 1
0.0296 1 1
0.0133 0.4885 0.4885
0.2611 1 0.5
0.0735 1 0.5
0.0926 1 0.5
0.0404 0.2633 1
0.2552 1 1
0.255 0.4262 0.5
0.0986 0.9156 1
0.3317 1 1
0.3001 1 0.5
0.033 1 0.5
0.6248 1 0.5
0.0295 1 0.5
0.1977 1 1
0.033 1 0.5
0.0885 1 0.5
0.1871 0.253 1
0.0328 1 0.5
0.0165 1 1
0.6248 1 0.5
0.268 1 0.5
0.2089 0.258 1
0.6681 1 1
0.1103 1 0.5
0.0469 0.2961 0.6469
0.0376 0.3358 0.5
0.3265 1 0.5
0.0165 0.5 0.5
0.2604 0.2872 1
0.1328 1 1
0.0982 0.6966 1
0.1444 1 1
0.2383 1 0.5
0.0136 1 1
0.0134 0.2854 0.3718
0.0737 0.4514 1
0.0165 0.9857 0.5
0.1138 1 0.5
0.0398 0.2926 1
0.0165 1 0.5
0.0137 0.3803 1
0.3067 1 0.5
0.1043 1 0.5
2.7753 0.7973 0.8249
0.1475 1 1
0.0165 1 1
0.0165 0.3169 1
0.2432 0.2865 1
0.0442 0.34 1
0.033 1 0.5
0.2584 0.8337 1
0.3466 1 1
0.2019 1 1
0.0137 0.3803 1
0.4549 1 1
0.0558 0.4451 1
0.4198 1 0.5
0.1271 0.3699 1
0.1517 1 1
0.2019 1 1
0.3296 1 0.5
0.4256 1 1
0.3169 0.8784 1
0.0602 1 0.5
0.4131 1 0.5
0.2761 1 0.5
0.0757 0.2675 0.328
0.66 1 0.5
0.0133 0.3087 0.5
0.336 1 0.5
0.2524 1 1
0.033 1 0.5
0.2604 0.2872 1
0.6145 1 0.5
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