{"uniprot":"Q96AZ1","gene":"EEF1AKMT3","name":"EEF1A lysine methyltransferase 3","organism":"Homo sapiens (Human)","status":"dark","length":226,"sequence":"MADPGPDPESESESVFPREVGLFADSYSEKSQFCFCGHVLTITQNFGSRLGVAARVWDAALSLCNYFESQNVDFRGKKVIELGAGTGIVGILAALQGGDVTITDLPLALEQIQGNVQANVPAGGQAQVRALSWGIDHHVFPANYDLVLGADIVYLEPTFPLLLGTLQHLCRPHGTIYLASKMRKEHGTESFFQHLLPQHFQLELAQRDEDENVNIYRARHREPRPA","function_summary":"A SAM-dependent lysine-directed methyltransferase that modifies protein substrates by lysine methylation and operates within multiprotein assemblies across the cytoplasm and nucleus. It likely fine-tunes chromatin and cytoskeletal systems by methylating histones and centrosome-associated proteins, with heat shock protein interactions guiding substrate selection and assembly localization. Its activity is concentrated in nucleoplasm and at the centrosome and chromosome-associated hubs, where methylation modulates complex formation and cell-cycle–linked regulation.","plain_language":"EEF1AKMT3 has barely been studied. The model's best guess: A SAM-dependent lysine-directed methyltransferase that modifies protein substrates by lysine methylation and operates within multiprotein assemblies across the cytoplasm and nucleus. It likely fine-tunes chromatin and cytoskeletal systems by methylating histones and centrosome-associated proteins, with heat shock protein interactions guiding substrate selection and assembly localization.","uniprot_summary":"Protein-lysine methyltransferase.","go_terms":{"molecular_function":[{"id":"GO:0016271","label":"protein-lysine N-methyltransferase activity"},{"id":"GO:0005515","label":"protein binding"},{"id":"GO:0031072","label":"heat shock protein binding"}],"biological_process":[{"id":"GO:0018022","label":"peptidyl-lysine methylation"}],"cellular_component":[{"id":"GO:0032991","label":"protein-containing complex"},{"id":"GO:0005737","label":"cytoplasm"},{"id":"GO:0005654","label":"nucleoplasm"},{"id":"GO:0005813","label":"centrosome"},{"id":"GO:0005694","label":"chromosome"}]},"interpro":[{"id":"IPR029063","name":"S-adenosyl-L-methionine-dependent methyltransferase superfamily","type":"homologous_superfamily","start":24,"end":226},{"id":"IPR019410","name":"Lysine methyltransferase","type":"family","start":28,"end":209}],"reasoning":"I begin with the InterPro architecture. The core of the protein is defined by IPR029063 (S-adenosyl-L-methionine-dependent methyltransferase superfamily, residues 24–226), a Rossmann-like fold that binds S-adenosyl-L-methionine (SAM) and catalyzes methyl transfer. Nested within this catalytic scaffold is IPR019410 (Lysine methyltransferase family, residues 28–209), which specifies substrate chemistry: transfer of a methyl group to the ε-amino group of lysine residues on proteins. The ordered embedding of a lysine-directed family signature inside a SAM-dependent catalytic core dictates a SAM-dependent protein-lysine N-methyltransferase. This architecture causes GO:0016271 protein-lysine N-methyltransferase activity and supports GO:0005515 protein binding through the typical substrate-recognition surfaces of this enzyme family.\n\nFrom this catalytic identity, the immediate biological role follows. Lysine methylation on target proteins constitutes GO:0018022 peptidyl-lysine methylation. The enzyme’s chemistry—using SAM to methylate specific lysines—fits a model in which it modifies histones and non-histone substrates to tune their interactions and activities.\n\nCellular context refines the mechanism. The presence in GO:0005737 cytoplasm and GO:0005654 nucleoplasm aligns with a shuttling enzyme that acts both on chromatin-associated and cytosolic targets. Localization to GO:0005813 centrosome and GO:0005694 chromosome indicates specialized roles in cell-cycle and chromatin-regulatory hubs. The association with GO:0032991 protein-containing complex is expected for a methyltransferase that operates within assemblies such as chromatin, centrosomal scaffolds, and cytoskeletal regulators.\n\nThe GO:0031072 heat shock protein binding term integrates naturally with this framework. Heat shock proteins (HSPs) chaperone misfolded or assembly-prone substrates and often guide methylation machinery to its targets. HSP binding would transiently recruit the enzyme to stress-responsive assemblies and centrosomal complexes, ensuring methylation occurs on correctly presented substrates.\n\nMechanistically, the SAM-dependent core binds SAM and positions a lysine side chain for nucleophilic attack, generating S-adenosyl-L-homocysteine and a mono-/di-/trimethyllysine on the substrate. Substrate preference is steered by the lysine-methyltransferase family determinants and by complex-associated adaptors. In the nucleus, this chemistry can methylate histones to modulate chromatin states; at the centrosome, it can tune centrosomal and cytoskeletal proteins to influence microtubule organization and cell-cycle transitions.\n\nI therefore hypothesize that the enzyme forms transient assemblies with heat shock proteins to chaperone and present substrates. Likely partners include HSP70/HSP90 systems that stabilize both histones and centrosomal scaffolds, as well as chromatin and centrosome-associated complexes. This cooperative targeting explains its dual cytoplasmic–nuclear distribution and its enrichment at chromosomes and the centrosome, where methylation of lysine residues modulates higher-order assemblies and signaling pathways.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q96AZ1.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q96AZ1"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q96AZ1/entry","atlas":"/p/Q96AZ1"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}