KSR2

KSR2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2Y4I
Identifiers
Aliases	KSR2, kinase suppressor of ras 2
External IDs	OMIM: 610737; MGI: 3610315; HomoloGene: 45469; GeneCards: KSR2; OMA:KSR2 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.22-q24.23 Start 117,453,012 bp[1] End 117,968,990 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 F Start 117,552,065 bp[2] End 117,913,068 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 middle temporal gyrus postcentral gyrus endothelial cell entorhinal cortex superior frontal gyrus primary visual cortex buccal mucosa cell cerebellar vermis Brodmann area 46 Top expressed in zygote dentate gyrus of hippocampal formation granule cell primary visual cortex superior frontal gyrus cerebellar cortex secondary oocyte lumbar subsegment of spinal cord neural layer of retina hippocampus proper amygdala More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity nucleotide binding protein serine/threonine kinase activity ATP binding metal ion binding kinase activity protein kinase activity signal transducer activity protein binding Cellular component cytoplasm membrane cytosol plasma membrane Biological process intracellular signal transduction phosphorylation protein phosphorylation Ras protein signal transduction calcium-mediated signaling positive regulation of MAPK cascade positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 283455 333050 Ensembl ENSG00000171435 ENSMUSG00000061578 UniProt Q6VAB6 Q3UVC0 RefSeq (mRNA) NM_173598 NM_001034873 NM_001114545 NM_001312914 RefSeq (protein) NP_775869 NP_001299843 Location (UCSC) Chr 12: 117.45 – 117.97 Mb Chr 5: 117.55 – 117.91 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

See also

• KSR1

References

1. GRCh38: Ensembl release 89: ENSG00000171435 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000061578 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "KSR2". Entrez Gene.
6. Pearce LR, Atanassova N, Banton MC, Bottomley B, van der Klaauw AA, Revelli JP, et al. (November 2013). "KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation". Cell. 155 (4): 765–777. doi:10.1016/j.cell.2013.09.058. PMC 3898740. PMID 24209692.
7. Huang Z, Tian Z, Zhao Y, Zhu F, Liu W, Wang X (May 2022). "MAPK Signaling Pathway Is Essential for Female Reproductive Regulation in the Cabbage Beetle, Colaphellus bowringi". Cells. 11 (10): 1602. doi:10.3390/cells11101602. PMC 9140119. PMID 35626638.