{"uniprot":"Q96LW2","gene":"RSKR","name":"Ribosomal protein S6 kinase-related protein","organism":"Homo sapiens (Human)","status":"dark","length":410,"sequence":"MGAVSCRQGQHTQQGEHTRVAVPHKQGGNIRGPWARGWKSLWTGLGTIRSDLEELWELRGHHYLHQESLKPAPVLVEKPLPEWPVPQFINLFLPEFPIRPIRGQQQLKILGLVAKGSFGTVLKVLDCTQKAVFAVKVVPKVKVLQRDTVRQCKEEVSIQRQINHPFVHSLGDSWQGKRHLFIMCSYCSTDLYSLWSAVGCFPEASIRLFAAELVLVLCYLHDLGIMHRDVKMENILLDERGHLKLTDFGLSRHVPQGAQAYTICGTLQYMAPEVLSGGPYNHAADWWSLGVLLFSLATGKFPVAAERDHVAMLASVTHSDSEIPASLNQGLSLLLHELLCQNPLHRLRYLHHFQVHPFFRGVAFDPELLQKQPVNFVTETQATQPSSAETMPFDDFDCDLESFLLYPIPA","function_summary":"A soluble serine/threonine kinase that operates within mitochondria to regulate phosphorylation-dependent signaling and metabolism. Its AGC-class catalytic core binds ATP and transfers phosphate to specific substrates, reshaping mitochondrial pathways by modulating enzyme activity and macromolecular assemblies. Through multivalent protein interactions and activation-loop–driven control, it coordinates phosphorylation programs that tune mitochondrial function and integrate organellar signals with broader cellular processes.","plain_language":"RSKR has barely been studied. The model's best guess: A soluble serine/threonine kinase that operates within mitochondria to regulate phosphorylation-dependent signaling and metabolism. Its AGC-class catalytic core binds ATP and transfers phosphate to specific substrates, reshaping mitochondrial pathways by modulating enzyme activity and macromolecular assemblies.","uniprot_summary":"Probable protein kinase that may be involved in mitochondrial signaling pathways.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006468","label":"protein phosphorylation"}],"cellular_component":[{"id":"GO:0005739","label":"mitochondrion"}]},"interpro":[{"id":"IPR011009","name":"Protein kinase-like domain superfamily","type":"homologous_superfamily","start":92,"end":388},{"id":"IPR000719","name":"Protein kinase domain","type":"domain","start":107,"end":359},{"id":"IPR045270","name":"Serine/Threonine Kinase AGC, catalytic domain","type":"domain","start":115,"end":359},{"id":"IPR008271","name":"Serine/threonine-protein kinase, active site","type":"active_site","start":225,"end":237}],"reasoning":"I begin with the InterPro architecture. The core of the protein is a bilobal kinase engine: IPR011009 (Protein kinase-like domain superfamily, residues 92–388) frames the overall fold, within which sits IPR000719 (Protein kinase domain, residues 107–359) and the more specific IPR045270 (Serine/Threonine Kinase AGC, catalytic domain, residues 115–359). The catalytic heart is pinpointed by IPR008271 (Serine/threonine-protein kinase, active site, residues 225–237), marking the catalytic loop that coordinates Mg2+-ATP and transfers phosphate to serine/threonine residues. This ordered arrangement—AGC-class catalytic core embedded in a canonical kinase scaffold—causally establishes a serine/threonine protein kinase that binds ATP and protein substrates. The AGC signature predicts regulation by activation-loop phosphorylation and docking interactions that enable selective protein binding.\n\nFrom this architecture, the molecular function resolves into two layers. First, the presence of the conserved active site and AGC catalytic domain necessitates ATP-dependent phosphotransfer, i.e., protein kinase activity and ATP binding. Second, the broad surface of the kinase fold and AGC regulatory elements promote multivalent protein binding, consistent with GO:0005515 protein binding. Together, these features drive GO:0006468 protein phosphorylation as the primary biological process: the enzyme modifies target proteins to modulate their activity, localization, or assembly.\n\nCellular placement follows from function and sequence context. The soluble kinase core lacks transmembrane segments and is compatible with matrix/cytosolic environments. The explicit evidence points to a mitochondrial role: a kinase of this class operating within mitochondria can tune metabolic and stress-response pathways by phosphorylating resident enzymes and RNA/protein assembly factors. This supports GO:0005739 mitochondrion as the cellular component and explains how phosphorylation within the organelle can reshape bioenergetic and quality-control circuits.\n\nMechanistically, the AGC kinase domain suggests a regulatory scheme in which activation-loop phosphorylation and docking interactions recruit mitochondrial substrates. By binding ATP and coordinating divalent cations at residues 225–237, the enzyme transfers phosphate to serine/threonine sites on mitochondrial targets, thereby altering their stability, activity, or interaction networks. This phosphorylation program can gate assembly of respiratory complexes, tune metabolic flux, and couple mitochondrial signaling to cytosolic pathways.\n\nGiven this mitochondrial kinase framework, likely interaction partners include mitochondrial protein complexes and adaptors that present substrates and scaffold assemblies. I hypothesize transient associations with the mitochondrial outer-membrane–associated machinery and matrix assemblies that coordinate phosphorylation: TOMM20 as an import/adaptor hub that can recruit soluble kinase cargo; VDAC1 at the outer membrane where signaling inputs converge; and matrix-localized assemblies such as the mitochondrial ribosome and RNA-processing factors that serve as phosphorylation targets. Additional docking with chaperonins (HSP60/HSPD1) and assembly factors would stabilize kinase–substrate encounters and localize signaling to the mitochondrial interior.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q96LW2.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q96LW2"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q96LW2/entry","atlas":"/p/Q96LW2"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}