Detailed view for PF3D7_1138400

Basic information

TDR Targets ID: 1863
Plasmodium falciparum, guanylyl cyclase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.2327 | Length (AA): 4226 | MW (Da): 496021 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 19

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

PF00122   E1-E2 ATPase
PF00211   Adenylate and Guanylate cyclase catalytic domain
PF16209   Phospholipid-translocating ATPase N-terminal
PF16212   Phospholipid-translocating P-type ATPase C-terminal

Gene Ontology

Mouse over links to read term descriptions.
GO:0035556   GO:intracellular signal transduction  

GO:0016021   integral to membrane  
GO:0016020   membrane  
GO:0005887   integral to plasma membrane  
GO:0004012   phospholipid-translocating ATPase activity  
GO:0003824   catalytic activity  
GO:0000287   magnesium ion binding  
GO:0016849   phosphorus-oxygen lyase activity  
GO:0005524   ATP binding  
GO:0004383   guanylate cyclase activity  
GO:0015914   phospholipid transport  
GO:0009190   cyclic nucleotide biosynthetic process  
GO:0008152   metabolic process  
GO:0007242   intracellular signaling cascade  
GO:0006754   ATP biosynthetic process  
GO:0006182   cGMP biosynthetic process  

Metabolic Pathways

Purine metabolism (KEGG)

Structural information

Modbase 3D models:

There are 22 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
2090 2334 1fft (A) 305 545 10.00 0.000000011 0.01 0.09 -0.77
3234 3316 1cjv (B) 995 1077 43.00 0.000000038 0.75 0.44 0.05
3964 4154 1yk9 (A) 245 425 30.00 0 1 0.38 -0.17
3966 4122 1azs (A) 387 536 36.00 0 1 0.59 -1.49
782 1035 4u0r (A) 182 492 20.00 0.05 0.04 0.280604 -0.6
3202 3319 2wz1 (A) 486 608 26.00 0.16 0.52 0.289722 -0.35
3226 3316 1azs (B) 987 1077 36.00 0.22 0.93 0.423333 0.06
3233 3315 3et6 (A) 568 651 53.00 0.00000000005 0.87 0.56594 0.43
3480 3742 4wat (A) 152 501 26.00 0.0015 0.66 0.130534 0.3
3961 4155 2wz1 (A) 412 609 26.00 0 1 0.354643 -0.82
3961 4140 4ni2 (A) 472 642 35.00 0 0.97 0.461093 -0.65
3964 4150 1azs (B) 880 1075 28.00 0 1 0.34975 -0.59
656 954 4o87 (A) 14 311 26.00 0.0086 0.84 0.246754 0.21
782 1035 4u0r (A) 182 492 20.00 0.078 0.02 0.274975 -0.63
2437 2716 2fds (A) 2 324 18.00 0.041 0.44 0.145145 -0.35
2599 2786 4cbe (A) 7 201 15.00 0.37 0.16 0.214313 -0.64
3189 3306 4p2f (A) 309 425 29.00 0.0031 0.86 0.414902 -0.37
3214 3303 1azs (B) 987 1076 37.00 0.5 0.96 0.452257 0.09
3221 3303 3et6 (A) 568 651 53.00 0.00000000005 0.87 0.566496 0.43
3468 3730 4wat (A) 152 501 26.00 0.0015 0.66 0.131211 0.3
3949 4143 2wz1 (A) 412 609 26.00 0 1 0.320974 -0.55
3954 4110 1azs (A) 387 536 36.00 0 1 0.561057 -1.11

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

Orthologs

Ortholog group members (OG5_133188)

Species Accession Gene Product
Babesia bovis BBOV_I000770   adenylate and guanylate cyclase catalytic domain containing protein
Cryptosporidium hominis Chro.30141   guanylyl cyclase-related
Cryptosporidium parvum cgd3_1110   P-type ATpase fused to two adenyl cyclase domains and 21 predicted transmembrane regions
Neospora caninum NCLIV_008660   adenylate and guanylate cyclase catalytic domain- containing protein, putative
Plasmodium berghei PBANKA_0910300   guanylyl cyclase, putative
Plasmodium falciparum PF3D7_1138400   guanylyl cyclase
Plasmodium knowlesi PKNH_0936600   guanylyl cyclase, putative
Plasmodium vivax PVX_092535   Adenylate and Guanylate cyclase catalytic domain containing protein
Plasmodium yoelii PY04459   guanylyl cyclase-related
Plasmodium yoelii PY04450   guanylyl cyclase-related
Plasmodium yoelii PY04451   guanylyl cyclase-related
Toxoplasma gondii TGME49_254370   guanylyl cyclase
Theileria parva TP02_0848   guanylyl cyclase, putative

Essentiality

PF3D7_1138400 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
PBANKA_0910300 Plasmodium berghei Slow plasmo
TGME49_254370 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
  • 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
  • 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
  • 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.
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

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): 0.5

Known modulators for this target

No chemical compounds associated to this gene

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

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

8 literature references were collected for this gene.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

User comments

No user comments are available for this gene. Log in to add comments, or register.

Enter your comment

User ()
Gene identifier PF3D7_1138400 (Plasmodium falciparum), guanylyl cyclase
Title for this comment
Comment