Farnesyl pyrophosphate synthase (FDPS)
The protein contains 419 amino acids for an estimated molecular weight of 48275 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs41314549 | |
| dbSNP:rs17456 | |
| POROK9 |
The reference OMIM entry for this protein is 134629
Farnesyl diphosphate synthase; fdps
Farnesylpyrophosphate synthetase; fps
DESCRIPTION
The isoprene biosynthetic pathway provides the cell with cholesterol, ubiquinone, dolichol, and other nonsterol metabolites. Farnesylpyrophosphate synthetase (EC 2.5.1.10) catalyzes the formation of both geranyl and farnesylpyrophosphate from isopentenylpyrophosphate and dimethylallyl pyrophosphate.CLONING
Sheares et al. (1989) isolated and characterized a partial length cDNA encoding FDPS. Wilkin et al. (1990) isolated and sequenced human cDNA for this enzyme in the cholesterogenic pathway. Regulation of FDPS mRNA levels parallels the regulation of mRNA levels for both HMG-CoA synthase (142940) and HMG-CoA reductase (142910). Wilkin et al. (1990) found that the mRNA levels for these enzymes were regulated in a coordinate manner by phorbol esters.GENE FUNCTION
By analysis of FDPS activity and protein in fractionated rat liver, together with immunofluorescence and immunoelectron microscopy studies, Krisans et al. (1994) demonstrated that FDPS is largely localized in peroxisomes. They found that liver tissue from patients with the peroxisomal deficiency diseases Zellweger syndrome (see 214100) and neonatal adrenoleukodystrophy (see 601539) contained reduced activities of FDPS and 4 other enzymes involved in isoprenoid synthesis. They proposed that these enzymes are localized in peroxisomes.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the FDPS gene to chromosome 1 (TMAP SHGC-2651). Several genes with high sequence similarity to FDPS have been identified (Sparkes et al., 1987; Heinzmann et al., 1989), all of which have been found to be pseudogenes (Scott, 2006). - Pseudogenes By plus/minus screening of a rat liver cDNA library, Sparkes et al. (1987) identified a gene that was coordinately regulated with HMG-CoA reductase (142910) and HMG-CoA synthase (142940), suggesting that it may be involved in cholesterol synthesis. It was provisionally identified as cholesterol repressible protein-39. Using somatic cell hybrids and in situ hybridization, Sparkes et al. (1987) mapped cholesterol repressible protein genes in the human to 3 chromosomes: 1q24-q31 (CHR39A, later determined to be the same as FDPSL1), 15q15-q21 (CHR39B, later determined to be the same as FDPSL4), and Xq13-q21 (CHR39C, later determined to be the same as FDPSL5). Heinzmann et al. (1989) reported that the mouse and human genomes contain multiple copies of genes with a high degree of sequence similarity to farnesyl diphosphate synthase. One or more of these may correspond to related phenyltransferases that catalyze the formation of nonsterol isoprene compounds. In the human, by analysis of somatic hybrids and by in situ hybridization (in the case of 3 of the 5 loci), Heinzmann et al. (1989) localized 5 loci designated as FDPS-like genes: FDPSL1 to 1q24-q31, FDPSL2 to chromosome 7, FDPSL3 to chromosome 14, FDPSL4 to 15q14-q21, and FDPSL5 to Xq21-q22. All of these transcripts have been found to be pseudogenes (Scott, 2006). ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 134629 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed