Tclin FDPS Farnesyl pyrophosphate synthase

Protein Summary

Description

Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate. This gene encodes an enzyme that catalyzes the production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The resulting product, farnesyl pyrophosphate, is a key intermediate in cholesterol and sterol biosynthesis, a substrate for protein farnesylation and geranylgeranylation, and a ligand or agonist for certain hormone receptors and growth receptors. Drugs that inhibit this enzyme prevent the post-translational modifications of small GTPases and have been used to treat diseases related to bone resorption. Multiple pseudogenes have been found on chromosomes 1, 7, 14, 15, 21 and X. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

Uniprot Accession IDs

• P14324
• D3DV91
• E9PCI9
• Q96G29
• FPP synthase

Gene Name

• FDPS

Ensembl ID

• ENST00000356657
• ENSP00000349078
• ENSG00000160752
• ENST00000368356
• ENSP00000357340
• ENST00000447866
• ENSP00000391755
• ENST00000467076
• ENSP00000480142
• ENST00000612683
• ENSP00000478235

Symbol

• FPS
• KIAA1293
• FPS
• FPPS
• POROK9

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	0.88
kinase perturbation	0.81
ligand (chemical)	0.8
transcription factor perturbation	0.74
small molecule perturbation	0.71

Protein Classes

PANTHER Classes

Protein / Transferase / Acyltransferase / Farnesyl Pyrophosphate Synthase

DTO Classes

Protein / Enzyme / Transferase / Acyltransferase / Farnesyl Pyrophosphate Synthase

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 623.08   (req: < 5)

Gene RIFs: 28   (req: <= 3)

Antibodies: 349   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 623.08   (req: >= 5)

Gene RIFs: 28   (req: > 3)

Antibodies: 349   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 9

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 213

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 6

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (6)

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1 – 6 of 6

zoledronic acid

FDPSTclin Enzyme

INHIBITOR pKi : 10.15

ibandronic acid

FDPSTclin Enzyme

INHIBITOR pKi : 8.44

alendronic acid

FDPSTclin Enzyme

INHIBITOR pKi : 7.35

pamidronic acid

FDPSTclin Enzyme

INHIBITOR pKi : 7.25

risedronic acid

FDPSTclin Enzyme

INHIBITOR pKi : 9.44

incadronic acid

FDPSTclin Enzyme

INHIBITOR pIC50 : 7.52

Active Ligands (213)

Explore Active Ligands

1 – 10 of 213

isopentenyl diphosphate

FDPSTclin Enzyme

pKi : 4.8

cimadronate

FDPSTclin Enzyme

pKi : 7.21

Minodronate

FDPSTclin Enzyme

pIC50 : 8.72

NE21650

FDPSTclin Enzyme

pKi : 7.19

BPH-252

FDPSTclin Enzyme

pKi : 6.64

BPH-715

FDPSTclin Enzyme

pIC50 : 7

(1-Hydroxy-1-phosphono-dodecyl)-phosphonic acid

FDPSTclin Enzyme

pKi : 6.13

[(5-Chloro-pyridin-2-ylamino)-phosphono-methyl]-phosphonic acid

FDPSTclin Enzyme

pKi : 7.64

(2-phenylthieno[2,3-d]pyrimidin-4-ylamino)methylenediphosphonic acid

FDPSTclin Enzyme

pIC50 : 7.09

CHEMBL4564934

FDPSTclin Enzyme

pIC50 : 7.07

Protein-Protein Interactions (141)

Explore Interacting Targets

1 – 10 of 141

• See Interactions on String-DB

PDSS2

Tbio

Family:  Enzyme

Novelty:  0.02716477

p_int:  0.999953011

p_ni:  0.000046978

p_wrong:  1e-8

Score:  0.963

Data Source:  BioPlex,STRINGDB

PCYOX1

Tbio

Family:  Enzyme

Novelty:  0.18505748

p_int:  0.996506739

p_ni:  0.003493261

Score:  0.278

Data Source:  BioPlex,STRINGDB

CLPP

Tchem

Family:  Enzyme

Novelty:  0.00105289

p_int:  0.996503496

p_ni:  0.003496504

Score:  0.284

Data Source:  BioPlex,STRINGDB

ZMPSTE24

Tbio

Family:  Enzyme

Novelty:  0.0027993

p_int:  0.990153026

p_ni:  0.009846961

p_wrong:  1.3e-8

Score:  0.287

Data Source:  BioPlex,STRINGDB

CDC27

Tbio

Novelty:  0.00589846

p_int:  0.977852079

p_ni:  0.022131894

p_wrong:  0.000016027

Score:  0.158

Data Source:  BioPlex,STRINGDB

TTC19

Tbio

Novelty:  0.08251578

p_int:  0.959773473

p_ni:  0.040226524

p_wrong:  3e-9

Score:  0.158

Data Source:  BioPlex,STRINGDB

PDSS1

Tbio

Family:  Enzyme

Novelty:  0.01542427

p_int:  0.954849519

p_ni:  0.00040228

p_wrong:  0.0447482

Score:  0.977

Data Source:  BioPlex,STRINGDB

ALAS1

Tclin

Family:  Enzyme

Novelty:  0.00965779

p_int:  0.937024066

p_ni:  0.062099931

p_wrong:  0.000876003

Score:  0.183

Data Source:  BioPlex,STRINGDB

PSME4

Tbio

Novelty:  0.01206213

p_int:  0.899430943

p_ni:  0.100569057

Score:  0.177

Data Source:  BioPlex,STRINGDB

MMAB

Tbio

Family:  Enzyme

Novelty:  0.01681296

p_int:  0.891237456

p_ni:  0.108762539

p_wrong:  5e-9

Score:  0.189

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (20)

Reactome (6)

KEGG (4)

PathwayCommons (5)

UniProt (2)

WikiPathways (3)

Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)

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5

1 – 5 of 6

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of gene expression by SREBF (SREBP)	42 targets	R-HSA-2426168
Reactome	Cholesterol biosynthesis	25 targets	R-HSA-191273
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Metabolism of lipids	740 targets	R-HSA-556833
Reactome	Metabolism of steroids	151 targets	R-HSA-8957322

Name	Explore in Pharos	Explore in Source
Activation of gene expression by SREBF (SREBP)	42 targets	R-HSA-2426168
Cholesterol biosynthesis	25 targets	R-HSA-191273
Metabolism	2112 targets	R-HSA-1430728
Metabolism of lipids	740 targets	R-HSA-556833
Metabolism of steroids	151 targets	R-HSA-8957322

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (12)

Functions (4)

Components (3)

Processes (5)

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1 – 4 of 4

GO Term	Evidence	Assigned by
RNA binding	Inferred from High Throughput Direct Assay (HDA)	UniProtKB
dimethylallyltranstransferase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
geranyltranstransferase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations ()

No disease associations found

GWAS Traits (27)

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5

1 – 5 of 27

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
reticulocyte measurement	EFO_0010700	3	2	4		93.8
gastric carcinoma	EFO_0000178	2	2	0	1.3	90.8
reticulocyte count	EFO_0007986	6	2	10		89
red blood cell distribution width	EFO_0005192	2	2	2		85.2
hemoglobin measurement	EFO_0004509	1	2	2		83.6

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 27

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
reticulocyte measurement	EFO_0010700	4		93.8
gastric carcinoma	EFO_0000178	0	1.3	90.8
reticulocyte count	EFO_0007986	10		89
red blood cell distribution width	EFO_0005192	2		85.2
hemoglobin measurement	EFO_0004509	2		83.6

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Cholesterol biosynthesis
Cholesterol metabolism
Complete proteome
Cytoplasm
Disease mutation
Host-virus interaction
Isoprene biosynthesis

GWAS Trait Find Similar Targets

No Header	No Header
appendicular lean mass
blood urea nitrogen measurement
BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
body fat distribution
brain aneurysm
creatinine measurement
Crohn's disease
diastolic blood pressure
gastric adenocarcinoma

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	farnesyl diphosphate synthase	VGNC:539	457366
Macaque	farnesyl diphosphate synthase		717761
Mouse	farnesyl diphosphate synthetase	MGI:104888	110196
Rat	farnesyl diphosphate synthase	RGD:68953	83791
Dog	farnesyl diphosphate synthase	VGNC:40812	480129

Species	Name	OMA	EggNOG	Inparanoid
Chimp	farnesyl diphosphate synthase
Macaque	farnesyl diphosphate synthase
Mouse	farnesyl diphosphate synthetase
Rat	farnesyl diphosphate synthase
Dog	farnesyl diphosphate synthase

Publication Statistics

PubMed Score 623.08

PubMed score by year

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PubTator Score 351.03

PubTator score by year

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Related Publications

Text Mined References (57)

GeneRif Annotations (28)

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PMID	Year	Title