KSR2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | KSR2 , kinase suppressor of ras 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 610737; MGI: 3610315; HomoloGene: 45469; GeneCards: KSR2; OMA:KSR2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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KSR2 is a gene which encodes Kinase Suppressor of Ras 2 in humans. [5]
The encoded protein plays a role in energy homeostasis, including fatty acid oxidation, glucose metabolism and basal metabolic rate (BMR). As a result, subsequent mutations in this gene, albeit rare, have been linked to the development of early on-set obesity and insulin resistance.
Variations within the gene and its expression are hypothesized to play a key role in the phenotype of individuals with metabolic disease, alongside leptin-deficiency induced hyperphagia. While the exact mechanism is unclear, it is believed that KSR2 variations result in a disruption of the MAPK/ERK pathway, which can in turn lower the body's BMR. Since this normally accounts for about 70% of the total energy expenditure, a decrease results in excess energy storage, compared to an individual with a normal BMR on an isocaloric diet. [6]
Besides human metabolism, KSR2 is also crucial for ovarian development in the cabbage beetle Colaphellus bowringi . [7]
Resistin also known as adipose tissue-specific secretory factor (ADSF) or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein (XCP1) is a cysteine-rich peptide hormone derived from adipose tissue that in humans is encoded by the RETN gene.
Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the SLC2A4 gene. GLUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle. The first evidence for this distinct glucose transport protein was provided by David James in 1988. The gene that encodes GLUT4 was cloned and mapped in 1989.
GTP cyclohydrolase I (GTPCH) (EC 3.5.4.16) is a member of the GTP cyclohydrolase family of enzymes. GTPCH is part of the folate and biopterin biosynthesis pathways. It is responsible for the hydrolysis of guanosine triphosphate (GTP) to form 7,8-dihydroneopterin triphosphate (7,8-DHNP-3'-TP, 7,8-NH2-3'-TP).
11β-Hydroxysteroid dehydrogenase type 1, also known as cortisone reductase, is an NADPH-dependent enzyme highly expressed in key metabolic tissues including liver, adipose tissue, and the central nervous system. In these tissues, HSD11B1 reduces cortisone to the active hormone cortisol that activates glucocorticoid receptors. It belongs to the family of short-chain dehydrogenases. It is encoded by the HSD11B1 gene.
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-brown, 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.
Acyl-CoA dehydrogenase, C-2 to C-3 short chain is an enzyme that in humans is encoded by the ACADS gene. This gene encodes a tetrameric mitochondrial flavoprotein, which is a member of the acyl-CoA dehydrogenase family. This enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. The ACADS gene is associated with short-chain acyl-coenzyme A dehydrogenase deficiency.
Forkhead box protein C2 (FOXC2) also known as forkhead-related protein FKHL14 (FKHL14), transcription factor FKH-14, or mesenchyme fork head protein 1 (MFH1) is a protein that in humans is encoded by the FOXC2 gene. FOXC2 is a member of the fork head box (FOX) family of transcription factors.
Pyruvate dehydrogenase phosphatase catalytic subunit 1, also known as protein phosphatase 2C, is an enzyme that in humans is encoded by the PDP1 gene. PDPC 1 is an enzyme which serves to reverse the effects of pyruvate dehydrogenase kinase upon pyruvate dehydrogenase, activating pyruvate dehydrogenase.
GLUT5 is a fructose transporter expressed on the apical border of enterocytes in the small intestine. GLUT5 allows for fructose to be transported from the intestinal lumen into the enterocyte by facilitated diffusion due to fructose's high concentration in the intestinal lumen. GLUT5 is also expressed in skeletal muscle, testis, kidney, fat tissue (adipocytes), and brain.
SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene. SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells.
Endothelin 1 (ET-1), also known as preproendothelin-1 (PPET1), is a potent vasoconstrictor peptide produced by vascular endothelial cells, as well as by cells in the heart and kidney. The protein encoded by this gene – EDN1 – is proteolytically processed to release endothelin 1. Endothelin 1 is one of three isoforms of human endothelin.
Fatty acid-binding protein 2 (FABP2), also known as Intestinal-type fatty acid-binding protein (I-FABP), is a protein that in humans is encoded by the FABP2 gene.
Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial (PDK4) is an enzyme that in humans is encoded by the PDK4 gene. It codes for an isozyme of pyruvate dehydrogenase kinase.
Peroxisome proliferator-activated receptor gamma coactivator 1-beta is a protein that in humans is encoded by the PPARGC1B gene.
Adipose triglyceride lipase, also known as patatin-like phospholipase domain-containing protein 2 and ATGL, is an enzyme that in humans is encoded by the PNPLA2 gene. ATGL catalyses the first reaction of lipolysis, where triacylglycerols are hydrolysed to diacylglycerols.
Lipin-1 is a protein that in humans is encoded by the LPIN1 gene.
Chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), tazarotene-induced gene 2 protein (TIG2), or RAR-responsive protein TIG2 is a protein that in humans is encoded by the RARRES2 gene.
Glycerol-3-phosphate dehydrogenase 1 is an enzyme that is encoded by the GPD1 gene in humans.
Sestrin 3 is a protein that in humans is encoded by the SESN3 gene.
Serpin A12 is a glycoprotein that is a class A member of the serine protease inhibitor (serpin) family. In humans, Serpin A12 is encoded by the SERPINA12 gene.