| FOLR3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | FOLR3 , FR-G, FR-gamma, gamma-hFR, folate receptor 3 (gamma), folate receptor 3, folate receptor gamma, FRgamma | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 602469 HomoloGene: 88342 GeneCards: FOLR3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Folate receptor gamma is a protein that in humans is encoded by the FOLR3 gene. It is involved in up-take of folic acid. [3]
The FOLR multi-gene family (FOLR1, FOLR2 and FOLR3) is localized to chromosome 11q13.3–q14.1, and encodes the gene products FRα, β and γ, respectively. [4]
FOLR3 is localized in haematopoietic tissue, such as spleen and bone marrow, and is present as a secretory protein. FOLR3 expresses in humans rather than mice and rats. [3]
The FOLR3 gene is polymorphic due to a nonsense mutation resulting in a truncated protein; FRγ, which can bind folic acid. FOLR3 genes each consist of 5 exons, 4 introns and 1 promoter that encodes a single transcript. [3]
Expression of FOLR3 is correlated more strongly with plasma homocysteine(Hcy) than FOLR1 and FOLR2. FOLR3 may decrease plasma Hcy compared with other FOLRs. [4] It was demonstrated that FOLR3 can metabolize both intracellular Hcy and extracellular Hcy. These results indicate that an increase in FOLR3 may effectively ameliorate Hcy in the blood and weaken Hcy-induced toxicity, even in tissues with the low level of FOLR1 and FOLR2 expression. [4]
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division. As the human body cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements.
Methylenetetrahydrofolatereductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the MTHFR gene. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Natural variation in this gene is common in otherwise healthy people. Although some variants have been reported to influence susceptibility to occlusive vascular disease, neural tube defects, Alzheimer's disease and other forms of dementia, colon cancer, and acute leukemia, findings from small early studies have not been reproduced. Some mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency. Complex I deficiency with recessive spastic paraparesis has also been linked to MTHFR variants. In addition, the aberrant promoter hypermethylation of this gene is associated with male infertility and recurrent spontaneous abortion.
Methionine synthase also known as MS, MeSe, MTR is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms part of the S-adenosylmethionine (SAMe) biosynthesis and regeneration cycle, and is the enzyme responsible for linking the cycle to one-carbon metabolism via the folate cycle. There are two primary forms of this enzyme, the Vitamin B12 (cobalamin)-dependent (MetH) and independent (MetE) forms, although minimal core methionine synthases that do not fit cleanly into either category have also been described in some anaerobic bacteria. The two dominant forms of the enzymes appear to be evolutionary independent and rely on considerably different chemical mechanisms. Mammals and other higher eukaryotes express only the cobalamin-dependent form. In contrast, the distribution of the two forms in Archaeplastida (plants and algae) is more complex. Plants exclusively possess the cobalamin-independent form, while algae have either one of the two, depending on species. Many different microorganisms express both the cobalamin-dependent and cobalamin-independent forms.
Agouti-signaling protein is a protein that in humans is encoded by the ASIP gene. It is responsible for the distribution of melanin pigment in mammals. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte produces phaeomelanin, or eumelanin. This interaction is responsible for making distinct light and dark bands in the hairs of animals such as the agouti, which the gene is named after. In other species such as horses, agouti signalling is responsible for determining which parts of the body will be red or black. Mice with wildtype agouti will be grey, with each hair being partly yellow and partly black. Loss of function mutations in mice and other species cause black fur coloration, while mutations causing expression throughout the whole body in mice cause yellow fur and obesity.
Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. Signs of folate deficiency are often subtle. A low number of red blood cells (anemia) is a late finding in folate deficiency and folate deficiency anemia is the term given for this medical condition. It is characterized by the appearance of large-sized, abnormal red blood cells (megaloblasts), which form when there are inadequate stores of folic acid within the body.
Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefore, making it an important protein for tumor growth, survival and metastasis of cancer cells to other locations in the body.
Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the IGFBP3 gene. IGFBP-3 is one of six IGF binding proteins that have highly conserved structures and bind the insulin-like growth factors IGF-1 and IGF-2 with high affinity. IGFBP-7, sometimes included in this family, shares neither the conserved structural features nor the high IGF affinity. Instead, IGFBP-7 binds IGF1R, which blocks IGF-1 and IGF-2 binding, resulting in apoptosis.
Probable G-protein coupled receptor 158 (GPR158), also known as the metabotropic glycine receptor (mGlyR), is a protein that in humans is encoded by the GPR158 gene.
G-protein coupled receptor 3 is a protein that in humans is encoded by the GPR3 gene. The protein encoded by this gene is a member of the G protein-coupled receptor family of transmembrane receptors and is involved in signal transduction.
Folate receptor 1 is a protein that in humans is encoded by the FOLR1 gene.
Methionine synthase reductase, also known as MSR, is an enzyme that in humans is encoded by the MTRR gene.
Folylpolyglutamate synthase, mitochondrial is an enzyme that in humans is encoded by the FPGS gene.
Folate receptor beta is a protein that in humans is encoded by the FOLR2 gene.
Nicotinamide N-methyltransferase (NNMT) is an enzyme that in humans is encoded by the NNMT gene. NNMT catalyzes the methylation of nicotinamide and similar compounds using the methyl donor S-adenosyl methionine (SAM-e) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide.
Glycine N-methyltransferase is an enzyme that in humans is encoded by the GNMT gene.
ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4. This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential. In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival. Outside this role, the SLC25AC31 gene has not been implicated in any human disease.
Folate receptors bind folate and reduced folic acid derivatives and mediates delivery of tetrahydrofolate to the interior of cells. It is then converted from monoglutamate to polyglutamate forms - such as 5-methyltetrahydrofolate - as only monoglutamate forms can be transported across cell membranes. Polyglutamate forms are biologically active enzymatic cofactors required for many folate-dependent processes such as folate-dependent one-carbon metabolism. These proteins are attached to the membrane by a GPI anchor. A riboflavin-binding protein required for the transport of riboflavin to the developing oocyte in chicken also belong to this family.
NAD-dependent methylenetetrahydrofolate dehydrogenase 2-like protein (MTHFD2L), also known as bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, is an enzyme that in humans is encoded by the MTHFD2L gene on chromosome 4. This enzyme localizes to the inner mitochondrial membrane, where it performs the NADP+-dependent dehydrogenase/cyclohydrolase activity as part of the mitochondrial pathway to convert folate to formate. It is associated with fluctuations in cytokine secretion in response to viral infections and vaccines.
The proton-coupled folate transporter is a protein that in humans is encoded by the SLC46A1 gene. The major physiological roles of PCFTs are in mediating the intestinal absorption of folate, and its delivery to the central nervous system.
Zinc transporter ZIP9, also known as Zrt- and Irt-like protein 9 (ZIP9) and solute carrier family 39 member 9, is a protein that in humans is encoded by the SLC39A9 gene. This protein is the 9th member out of 14 ZIP family proteins, which is a membrane androgen receptor (mAR) coupled to G proteins, and also classified as a zinc transporter protein. ZIP family proteins transport zinc metal from the extracellular environment into cells through cell membrane.
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