FPGS
Folylpolyglutamate synthase, mitochondrial
Also known as: FOLC_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q05932
- Gene
- FPGS
- Ensembl
- ENSG00000136877
- Chromosome
- 9
- Canonical length
- 587 aa
- Protein class
- Enzymes, FDA approved drug targets, Metabolic proteins, Predicted intracellular proteins
- Secretome location
- Intracellular and membrane
OverviewNCBI Gene
This gene encodes the folylpolyglutamate synthetase enzyme. This enzyme has a central role in establishing and maintaining both cytosolic and mitochondrial folylpolyglutamate concentrations and, therefore, is essential for folate homeostasis and the survival of proliferating cells. This enzyme catalyzes the ATP-dependent addition of glutamate moieties to folate and folate derivatives. Alternative splicing results in transcript variants encoding different isoforms. [provided by RefSeq, Jan 2014]
Canonical amino-acid sequenceUniProt
587 residues, UniProt reviewed canonical sequence.
>Q05932|FPGS
1 MSRARSHLRA ALFLAAASAR GITTQVAARR GLSAWPVPQE PSMEYQDAVR MLNTLQTNAG
61 YLEQVKRQRG DPQTQLEAME LYLARSGLQV EDLDRLNIIH VTGTKGKGST CAFTECILRS
121 YGLKTGFFSS PHLVQVRERI RINGQPISPE LFTKYFWRLY HRLEETKDGS CVSMPPYFRF
181 LTLMAFHVFL QEKVDLAVVE VGIGGAYDCT NIIRKPVVCG VSSLGIDHTS LLGDTVEKIA
241 WQKGGIFKQG VPAFTVLQPE GPLAVLRDRA QQISCPLYLC PMLEALEEGG PPLTLGLEGE
301 HQRSNAALAL QLAHCWLQRQ DRHGAGEPKA SRPGLLWQLP LAPVFQPTSH MRLGLRNTEW
361 PGRTQVLRRG PLTWYLDGAH TASSAQACVR WFRQALQGRE RPSGGPEVRV LLFNATGDRD
421 PAALLKLLQP CQFDYAVFCP NLTEVSSTGN ADQQNFTVTL DQVLLRCLEH QQHWNHLDEE
481 QASPDLWSAP SPEPGGSASL LLAPHPPHTC SASSLVFSCI SHALQWISQG RDPIFQPPSP
541 PKGLLTHPVA HSGASILREA AAIHVLVTGS LHLVGGVLKL LEPALSQLocalizationUniProt · AlphaFold · HPA
Whether an antibody against FPGS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Other membrane
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.28
- Highest tissue expression
- 65 nTPM
Expression across tissuesHPA
Tissue
- liver: 65 nTPM
- ovary: 52 nTPM
- adrenal gland: 47 nTPM
- skeletal muscle: 46 nTPM
- adipose tissue: 35 nTPM
- breast: 32 nTPM
Single-cell type
- hepatocytes: 89 nCPM
- alveolar cells type 1: 63 nCPM
- esophageal apical cells: 63 nCPM
- ovarian stromal cells: 58 nCPM
- alveolar cells type 2: 55 nCPM
- endometrial luminal cells: 54 nCPM
Immune cell
- NK-cell: 44 nTPM
- gdT-cell: 39 nTPM
- plasmacytoid DC: 39 nTPM
- MAIT T-cell: 35 nTPM
- memory CD8 T-cell: 34 nTPM
- myeloid DC: 31 nTPM
Brain region
- medulla oblongata: 15 nTPM
- spinal cord: 15 nTPM
- white matter: 14 nTPM
- midbrain: 14 nTPM
- basal ganglia: 13 nTPM
- cerebral cortex: 13 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.74
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.89
- DepMap mean gene effect
- -0.42
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cell population proliferation
- folic acid metabolic process
- folic acid-containing compound metabolic process
- glutamate metabolic process
- nucleobase-containing compound metabolic process
- one-carbon metabolic process
- tetrahydrofolylpolyglutamate biosynthetic process
Molecular functions
- ATP binding
- metal ion binding
- tetrahydrofolylpolyglutamate synthase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Folylpolyglutamate synthetase
- Folylpolyglutamate synthetase, conserved site
- Folylpolyglutamate synthase, eukaryota
- Mur-like, catalytic domain superfamily
- Mur ligase, C-terminal domain superfamily
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads FPGS as an antibody target. Whether an autoantibody or antibody against FPGS could matter depends on whether native FPGS is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
FPGS is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label FPGS as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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