AGK (gene)
| AGK | |||
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| Identifiers | |||
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 7: 141.55 – 141.66 Mb | Chr 6: 40.3 – 40.37 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
The human gene AGK encodes the enzyme mitochondrial acylglycerol kinase.[5][6][7][8]
The protein encoded by this gene is a
Diseases associated with AGK include
Structure
The AGK gene is located on the 7th chromosome, with its specific location being 7q34. The gene contains 18 exons.[8] AGK encodes a 47.1 kDa protein that is composed of 422 amino acids; 32 peptides have been observed through mass spectrometry data.[9][10]
Function
Acylglycerol kinase synthesizes phosphatidic and lysophosphatidic acids. The enzyme uses ATP to put a phosphate group on acyl glycerol and diacylglycerol. It catalyzes the following reactions:
ATP + acylglycerol = ADP + acyl-sn-glycerol 3-phosphate. ATP + 1,2-diacyl-sn-glycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate.
The enzyme is involved in the more general pathway of fatty acid metabolism. AGK also has an implicated role in the assembly of the adenine nucleotide translocator in the inner mitochondrial membrane. [11]
Clinical significance
Mutations in the AGK gene were the first to be implicated in isolated
AGK expression has also been correlated with certain cancer phenotypes. AGK expression, in coordination with AGX, was not detected in non-neoplastic epithelia, while both were weakly expressed in the majority of high-grade intra-epithelial neoplasia (HG-PIN). Expressions of both enzymes were significantly correlated with primary Gleason grade of cancer foci and capsular invasion.[14] Overexpression of AGK sustains constitutive JAK2/STAT3 activation, consequently promoting the cancer stem cell population and augmenting the tumorigenicity of esophageal squamous cell carcinoma (ESCC) cells both in vivo and in vitro. Furthermore, AGK levels significantly increases STAT3 phosphorylation, poorer disease-free survival, and shorter overall survival in primary ESCC. More importantly, AGK expression was significantly correlated with JAK2/STAT3 hyperactivation in ESCC, as well as in lung and breast cancer.[15] In prostate cancer, AGK expression amplifies EGF signaling pathways, thus playing a significant role in the development of prostate cancer.[16] It's also correlated tumor-nodule-metastasis (TNM) classification breast cancer, and an overall shorter overall survival.[17]
Interactions
In the progression of diabetic retinopathy, the ATX-AGK-LPA signaling axis plays a significant role.[18]
In the proliferation of prostate cancer, AGK interacts with and regulates PC-3 prostate cancer cells markedly increased formation and secretion of LPA. This increase also affects the EGF receptor and sustained activation of extracellular signal related kinase (ERK) 1/2, culminating in enhanced cell proliferation.[16] Acylglycerol kinase also augments JAK2/STAT3 signaling in esophageal squamous cells.[15]
References
- ^ a b c ENSG00000262327 GRCh38: Ensembl release 89: ENSG00000006530, ENSG00000262327 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029916 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 15252046.
- PMID 15939762.
- PMID 17135245.
- ^ a b "Entrez Gene: AGK acylglycerol kinase".
- PMID 23965338.
- ^ "Acylglycerol kinase, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).[permanent dead link]
- PMID 22284826.
- S2CID 10579886.
- PMID 23266196.
- S2CID 27776078.
- ^ PMID 23676499.
- ^ PMID 15939762.
- PMID 24886245.
- S2CID 22594417.
External links
- Human AGK genome location and AGK gene details page in the UCSC Genome Browser.
Further reading
- Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. PMID 9373149.
- Van Overloop H, Gijsbers S, Van Veldhoven PP (Feb 2006). "Further characterization of mammalian ceramide kinase: substrate delivery and (stereo)specificity, tissue distribution, and subcellular localization studies". Journal of Lipid Research. 47 (2): 268–83. PMID 16269826.