Gene Ontology annotation through association of InterPro records with GO terms.
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping.
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.
Combined Automated Annotation using Multiple IEA Methods.
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
Skin-specific regulation of SREBP processing and lipid biosynthesis by glycerol kinase 5.
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GK5 is a skin-specific kinase expressed predominantly in sebaceous glands; loss of GK5 (toku allele) causes delayed hair growth, progressive hair loss, and excessive dermal cholesterol/triglyceride/ceramide accumulation.
"The recessive N-ethyl-N-nitrosourea-induced phenotype toku is characterized by delayed hair growth, progressive hair loss, and excessive accumulation of dermal cholesterol, triglycerides, and ceramides. The toku phenotype was attributed to a null allele of Gk5, encoding glycerol kinase 5 (GK5), a skin-specific kinase expressed predominantly in sebaceous glands."
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GK5 binds SREBP-1 and SREBP-2 via their C-terminal regulatory domains and inhibits SREBP proteolytic processing/activation; loss of GK5 in skin leads to nuclear accumulation of active SREBPs and elevated lipid synthesis. Kinase activity is required, since kinase-inactive GK5 phenocopies the null.
"GK5 formed a complex with the sterol regulatory element-binding proteins (SREBPs) through their C-terminal regulatory domains, inhibiting SREBP processing and activation. In Gk5toku/toku mice, transcriptionally active SREBPs accumulated in the skin, but not in the liver; they were localized to the nucleus and led to elevated lipid synthesis and subsequent hair growth defects. Similar defective hair growth was observed in kinase-inactive GK5 mutant mice."
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Phenotype of GK5-null mice is partially rescued by the HMG-CoA reductase inhibitor simvastatin, implicating overactive sterol biosynthesis as a driver of pathology; GK5 acts in a skin-specific cholesterol regulatory mechanism independent of systemic cholesterol control.
"Hair growth defects of homozygous toku mice were partially rescued by treatment with the HMG-CoA reductase inhibitor simvastatin. GK5 exists as part of a skin-specific regulatory mechanism for cholesterol biosynthesis, independent of cholesterol regulation elsewhere in the body."
Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway.
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GK5 mRNA and protein are upregulated in gefitinib-resistant NSCLC cells (PC9R, H1975) and in plasma exosomes from resistant patients; silencing GK5 induces mitochondrial damage, caspase activation, cell-cycle arrest and apoptosis via SREBP1/SCD1 signaling, supporting a pro-survival lipogenic role of GK5 in EGFR-TKI-resistant lung cancer.
"The mRNA and protein levels of GK5 were significantly upregulated in gefitinib-resistant human lung adenocarcinoma PC9R and H1975 cells compared with gefitinib-sensitive PC9 cells. Silencing GK5 in PC9R cells induced mitochondrial damage, caspase activation, cell cycle arrest, and apoptosis via SREBP1/SCD1 signaling pathway."
Glycerol kinase enzyme is a prognostic predictor in esophageal carcinoma and is associated with immune cell infiltration.
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Review/secondary citation that contextualizes GK5 among three glycerol-kinase variants (GK, GK2, GK5) and recapitulates the gefitinib-resistance/SREBP1-SCD1 phenotype originally reported by Zhou 2019; no GK5-specific primary data are presented (the quantitative ESCA analyses concern GK, not GK5).
"There are three GK variants: GK, GK2, and GK5. Glycerol Kinase 5 (GK5) is implicated in several processes, including the glycerol metabolic process. Notably, exosomal mRNA of GK5 in the plasma of patients with gefitinib-resistant adenocarcinoma is significantly higher than in gefitinib-sensitive patients."
Deep research on GK5 function
Deep research on GK5 function (falcon provider)
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Falcon synthesis confirms GK5 as an FGGY-family glycerol kinase with measurable glycerol kinase activity and emphasizes its tissue-specialized regulatory role in skin via direct binding to SREBP-1/2 C-terminal regulatory domains, inhibiting SREBP processing; SREBP binding is kinase-independent while the skin phenotype requires kinase activity. GK5 also heterodimerizes with GK (GK1) through N-terminal FGGY_N domains.
"GK5 binds glycerol kinase (GK) via N-terminal FGGY_N domains and associates with SREBP-1 and SREBP-2 through their C-terminal regulatory domains. Binding to SREBPs appears kinase-independent, and purified GK5 did not phosphorylate immunoprecipitated SREBPs."
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Falcon also collates translational evidence that GK5 acts downstream/upstream of SREBP1/SCD1 in gefitinib-resistant NSCLC, consistent with a lipogenic pro-survival role in cancer.
"In NSCLC, plasma exosomal GK5 mRNA was reported as significantly higher in gefitinib-resistant versus gefitinib-sensitive patients, and GK5 was upregulated in resistant PC9R/H1975 cells. GK5 silencing induced mitochondrial damage, caspase activation, cell-cycle arrest, and apoptosis via SREBP1/SCD1 signaling, suggesting biomarker and therapeutic-target potential."