{"gene":"GK2","run_date":"2026-04-28T18:06:53","timeline":{"discoveries":[{"year":1992,"finding":"GK2 encodes a human galactokinase (EC 2.7.1.6) of 458 amino acids, located on chromosome 15, with 29% identity to yeast galactokinase; its galactokinase activity was demonstrated by functional complementation of a galactokinase-deficient (gal1-) Saccharomyces cerevisiae strain.","method":"Functional complementation in yeast (gal1- strain rescue by human cDNA expression)","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 — direct enzymatic complementation assay establishing catalytic function","pmids":["1438294"],"is_preprint":false},{"year":1995,"finding":"GK2 cDNA expressed in COS cells produced only very low (or undetectable) galactokinase activity compared to GALK1, suggesting GK2 is not the primary enzyme for galactose metabolism in mammalian cells.","method":"Heterologous expression in COS cells with galactokinase activity assay and Northern blot","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — direct enzymatic assay in mammalian cells, single lab, single study","pmids":["7542884"],"is_preprint":false}],"current_model":"GK2 encodes a human galactokinase (EC 2.7.1.6) on chromosome 15 capable of complementing galactokinase-deficient yeast, but when expressed in mammalian (COS) cells it shows negligible galactokinase activity compared to GALK1, indicating it is not the primary enzyme for galactose metabolism and its physiological role remains uncertain."},"narrative":{"teleology":[{"year":1992,"claim":"Identification of GK2 as a human galactokinase-encoding gene resolved whether a second galactokinase locus existed in the human genome, establishing that GK2 possesses intrinsic galactokinase activity.","evidence":"Functional complementation of gal1- S. cerevisiae by human GK2 cDNA expression","pmids":["1438294"],"confidence":"High","gaps":["Activity was demonstrated only in yeast; mammalian cell activity was untested","Endogenous tissue expression pattern of GK2 was not determined","No comparison with GALK1 activity level was performed"]},{"year":1995,"claim":"Demonstrating that GK2 has negligible galactokinase activity in mammalian cells established that it is not the primary galactokinase and raised the question of whether it has an alternative physiological substrate or function.","evidence":"Heterologous expression in COS cells with galactokinase activity assay and Northern blot comparison to GALK1","pmids":["7542884"],"confidence":"Medium","gaps":["Single-lab observation not independently replicated in additional mammalian systems","No alternative substrates or binding partners were tested","Endogenous protein expression and tissue distribution remain uncharacterized"]},{"year":null,"claim":"The physiological role of GK2 in mammalian cells remains unknown — whether it acts on an alternative sugar substrate, functions in a specific tissue context, or has a non-catalytic role has not been addressed experimentally.","evidence":"","pmids":[],"confidence":"Low","gaps":["No substrate specificity profiling beyond galactose has been performed","No loss-of-function studies in mammalian models exist","No structural or interactome data are available"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0]}],"localization":[],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0]}],"complexes":[],"partners":[],"other_free_text":[]},"mechanistic_narrative":"GK2 encodes a 458-amino-acid protein with sequence homology to galactokinases (EC 2.7.1.6) that can complement galactokinase-deficient yeast, demonstrating intrinsic galactokinase catalytic capacity [PMID:1438294]. However, when expressed in mammalian COS cells, GK2 exhibits negligible galactokinase activity compared to GALK1, indicating it is not the primary galactokinase for galactose metabolism in mammalian cells, and its physiological function remains uncharacterized [PMID:7542884]."},"prefetch_data":{"uniprot":{"accession":"Q14410","full_name":"Glycerol kinase 2","aliases":["ATP:glycerol 3-phosphotransferase 2","Glycerol kinase, testis specific 2"],"length_aa":553,"mass_kda":60.6,"function":"Key enzyme in the regulation of glycerol uptake and metabolism. Essential for male fertility and sperm mitochondrial sheath formation (By similarity). Required for proper arrangement of crescent-like mitochondria to form the mitochondrial sheath during spermatogenesis (By similarity). Can induce mitochondrial clustering through interactions with PLD6 and up-regulation of phosphatidic acid synthesis in the mitochondria (PubMed:28852571)","subcellular_location":"Mitochondrion outer membrane; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q14410/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GK2","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/GK2","total_profiled":1310},"omim":[{"mim_id":"600149","title":"GLYCEROL KINASE 3 PSEUDOGENE; GK3P","url":"https://www.omim.org/entry/600149"},{"mim_id":"600148","title":"GLYCEROL KINASE 2; GK2","url":"https://www.omim.org/entry/600148"},{"mim_id":"137028","title":"GALACTOKINASE 2; GALK2","url":"https://www.omim.org/entry/137028"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"testis","ntpm":83.7}],"url":"https://www.proteinatlas.org/search/GK2"},"hgnc":{"alias_symbol":["GKTA"],"prev_symbol":["GKP2"]},"alphafold":{"accession":"Q14410","domains":[{"cath_id":"3.30.420.40","chopping":"11-267_451-482","consensus_level":"medium","plddt":94.8033,"start":11,"end":482},{"cath_id":"3.30.420.40","chopping":"319-449_485-509","consensus_level":"medium","plddt":93.3081,"start":319,"end":509}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14410","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q14410-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q14410-F1-predicted_aligned_error_v6.png","plddt_mean":92.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GK2","jax_strain_url":"https://www.jax.org/strain/search?query=GK2"},"sequence":{"accession":"Q14410","fasta_url":"https://rest.uniprot.org/uniprotkb/Q14410.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q14410/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14410"}},"corpus_meta":[{"pmid":"1438294","id":"PMC_1438294","title":"Cloning of a human galactokinase gene (GK2) on chromosome 15 by complementation in yeast.","date":"1992","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/1438294","citation_count":27,"is_preprint":false},{"pmid":"24303204","id":"PMC_24303204","title":"Original Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive Functions in Rat Models of Alzheimer's Disease.","date":"2013","source":"Acta naturae","url":"https://pubmed.ncbi.nlm.nih.gov/24303204","citation_count":17,"is_preprint":false},{"pmid":"26289852","id":"PMC_26289852","title":"Identification of a panel of complex autoantigens (LGALS3, PHB2, MUC1, and GK2) in combination with CA15-3 for the diagnosis of early-stage breast cancer.","date":"2015","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26289852","citation_count":16,"is_preprint":false},{"pmid":"24950445","id":"PMC_24950445","title":"Behavioral effect of dipeptide NGF mimetic GK-2 in an in vivo model of rat traumatic brain injury and its neuroprotective and regenerative properties in vitro.","date":"2014","source":"The International journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/24950445","citation_count":12,"is_preprint":false},{"pmid":"7542884","id":"PMC_7542884","title":"Comparison of the enzymatic activities of human galactokinase GALK1 and a related human galactokinase protein GK2.","date":"1995","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/7542884","citation_count":5,"is_preprint":false},{"pmid":"31024748","id":"PMC_31024748","title":"A Novel Dipeptide NGF Mimetic GK-2 Selectively Activating the PI3K/AKT Signaling Pathway Promotes the Survival of Pancreatic β-Cells in a Rat Model of Diabetes.","date":"2019","source":"Acta naturae","url":"https://pubmed.ncbi.nlm.nih.gov/31024748","citation_count":5,"is_preprint":false},{"pmid":"26388581","id":"PMC_26388581","title":"Effectiveness of GK-2, a Nerve Growth Factor Mimetic, in Preventing Post-Resuscitation Changes in the Brain.","date":"2015","source":"Bulletin of experimental biology and medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26388581","citation_count":4,"is_preprint":false},{"pmid":"36688733","id":"PMC_36688733","title":"Protective effect of GK2 fused BLVRA protein against oxidative stress-induced dopaminergic neuronal cell damage.","date":"2023","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/36688733","citation_count":1,"is_preprint":false},{"pmid":"35748804","id":"PMC_35748804","title":"Low molecular weight NGF mimetic GK-2 normalizes the parameters of glucose and lipid metabolism and exhibits a hepatoprotective effect on a prediabetes model in obese Wistar rats.","date":"2022","source":"Clinical and experimental pharmacology & physiology","url":"https://pubmed.ncbi.nlm.nih.gov/35748804","citation_count":1,"is_preprint":false},{"pmid":"41207346","id":"PMC_41207346","title":"Pharmacokinetics, tissue distribution, in vivo metabolism and liver microsomal metabolism of GK-A, GK-2 and Eucomic acid in rats were studied by liquid chromatography-tandem mass spectrometry and mass spectrometry imaging of Ginkgo semen extract.","date":"2025","source":"Journal of ethnopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41207346","citation_count":1,"is_preprint":false},{"pmid":"21395008","id":"PMC_21395008","title":"[Neuroprotective effect of low-molecular peptide mimetic (GK-2) of nerve growth factor is related to activated synthesis of heat shock proteins (hsp32 and hsp70) and increased phosphorylation of TrkA receptor].","date":"2010","source":"Eksperimental'naia i klinicheskaia farmakologiia","url":"https://pubmed.ncbi.nlm.nih.gov/21395008","citation_count":1,"is_preprint":false},{"pmid":"26571801","id":"PMC_26571801","title":"[Effect of the nerve growth factor mimetic GK-2 on post-resuscitation expression of neurotrophic factors].","date":"2015","source":"Patologicheskaia fiziologiia i eksperimental'naia terapiia","url":"https://pubmed.ncbi.nlm.nih.gov/26571801","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6965,"output_tokens":518,"usd":0.014332},"stage2":{"model":"claude-opus-4-6","input_tokens":3680,"output_tokens":817,"usd":0.058237},"total_usd":0.072569,"stage1_batch_id":"msgbatch_01DzrsgVgYngY1hvM3DU1yF2","stage2_batch_id":"msgbatch_01KA9b7iRzKFdhoBUT7vCvSe","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1992,\n      \"finding\": \"GK2 encodes a human galactokinase (EC 2.7.1.6) of 458 amino acids, located on chromosome 15, with 29% identity to yeast galactokinase; its galactokinase activity was demonstrated by functional complementation of a galactokinase-deficient (gal1-) Saccharomyces cerevisiae strain.\",\n      \"method\": \"Functional complementation in yeast (gal1- strain rescue by human cDNA expression)\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct enzymatic complementation assay establishing catalytic function\",\n      \"pmids\": [\"1438294\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"GK2 cDNA expressed in COS cells produced only very low (or undetectable) galactokinase activity compared to GALK1, suggesting GK2 is not the primary enzyme for galactose metabolism in mammalian cells.\",\n      \"method\": \"Heterologous expression in COS cells with galactokinase activity assay and Northern blot\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct enzymatic assay in mammalian cells, single lab, single study\",\n      \"pmids\": [\"7542884\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GK2 encodes a human galactokinase (EC 2.7.1.6) on chromosome 15 capable of complementing galactokinase-deficient yeast, but when expressed in mammalian (COS) cells it shows negligible galactokinase activity compared to GALK1, indicating it is not the primary enzyme for galactose metabolism and its physiological role remains uncertain.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"GK2 encodes a 458-amino-acid protein with sequence homology to galactokinases (EC 2.7.1.6) that can complement galactokinase-deficient yeast, demonstrating intrinsic galactokinase catalytic capacity [PMID:1438294]. However, when expressed in mammalian COS cells, GK2 exhibits negligible galactokinase activity compared to GALK1, indicating it is not the primary galactokinase for galactose metabolism in mammalian cells, and its physiological function remains uncharacterized [PMID:7542884].\",\n  \"teleology\": [\n    {\n      \"year\": 1992,\n      \"claim\": \"Identification of GK2 as a human galactokinase-encoding gene resolved whether a second galactokinase locus existed in the human genome, establishing that GK2 possesses intrinsic galactokinase activity.\",\n      \"evidence\": \"Functional complementation of gal1- S. cerevisiae by human GK2 cDNA expression\",\n      \"pmids\": [\"1438294\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Activity was demonstrated only in yeast; mammalian cell activity was untested\",\n        \"Endogenous tissue expression pattern of GK2 was not determined\",\n        \"No comparison with GALK1 activity level was performed\"\n      ]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Demonstrating that GK2 has negligible galactokinase activity in mammalian cells established that it is not the primary galactokinase and raised the question of whether it has an alternative physiological substrate or function.\",\n      \"evidence\": \"Heterologous expression in COS cells with galactokinase activity assay and Northern blot comparison to GALK1\",\n      \"pmids\": [\"7542884\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab observation not independently replicated in additional mammalian systems\",\n        \"No alternative substrates or binding partners were tested\",\n        \"Endogenous protein expression and tissue distribution remain uncharacterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological role of GK2 in mammalian cells remains unknown — whether it acts on an alternative sugar substrate, functions in a specific tissue context, or has a non-catalytic role has not been addressed experimentally.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No substrate specificity profiling beyond galactose has been performed\",\n        \"No loss-of-function studies in mammalian models exist\",\n        \"No structural or interactome data are available\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0016740\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-1430728\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```"}