{"uniprot":"Q4KMZ8","gene":"NKAIN1","name":"Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1","organism":"Homo sapiens (Human)","status":"dark","length":207,"sequence":"MGKCSGRCTLVAFCCLQLVAALERQIFDFLGYQWAPILANFLHIMAVILGIFGTVQYRSRYLILYAAWLVLWVGWNAFIICFYLEVGQLSQDRDFIMTFNTSLHRSWWMENGPGCLVTPVLNSRLALEDHHVISVTGCLLDYPYIEALSSALQIFLALFGFVFACYVSKVFLEEEDSFDFIGGFDSYGYQAPQKTSHLQLQPLYTSG","function_summary":"A single-pass membrane-associated regulator that binds ATPase complexes and modulates their assembly and activity at the cell surface. By anchoring to the plasma membrane and engaging pump assemblies, it fine-tunes ion transport systems and supports biogenesis of multisubunit proton pumps. This scaffolding role coordinates pump stabilization and trafficking, thereby coupling surface ion-handling pathways with lysosomal acidification machinery.","plain_language":"NKAIN1 has barely been studied. The model's best guess: A single-pass membrane-associated regulator that binds ATPase complexes and modulates their assembly and activity at the cell surface. By anchoring to the plasma membrane and engaging pump assemblies, it fine-tunes ion transport systems and supports biogenesis of multisubunit proton pumps.","uniprot_summary":"May modulate the activity of plasma membrane ATPase.","go_terms":{"molecular_function":[{"id":"GO:0051117","label":"ATPase binding"}],"biological_process":[{"id":"GO:0070070","label":"proton-transporting V-type ATPase complex assembly"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR008516","name":"Na,K-Atpase Interacting protein","type":"family","start":1,"end":206}],"reasoning":"I begin with the InterPro architecture: IPR008516 (Na,K-Atpase Interacting protein family) spans residues 1–206 and covers the entire polypeptide. A single full-length family signature without embedded catalytic domains indicates a non-enzymatic membrane-associated regulator that binds and modulates P-type ATPases. The family designation explicitly ties the protein to Na+/K+-ATPase systems, and the compact length is consistent with a single-pass membrane scaffold that stabilizes or tunes pump assemblies.\n\nThis architecture causally supports ATPase association as the core molecular function. The absence of catalytic motifs and the presence of a dedicated ATPase-interacting family domain argue that the protein binds and regulates ATPase complexes rather than performing transport itself. This directly aligns with GO:0051117 ATPase binding as the molecular function: the domain composition and membrane anchoring create a high-affinity platform for ATPase engagement.\n\nFrom this binding function, I infer the biological process by considering what assembly control accomplishes. The explicit link to V-type ATPase biogenesis is captured by GO:0070070 proton-transporting V-type ATPase complex assembly. A membrane scaffold that binds ATPases can chaperone or coordinate assembly of multisubunit proton pumps, especially during endo-lysosomal trafficking. The same binding chemistry that targets Na+/K+-ATPase can be repurposed to shepherd V-ATPase assembly steps, providing a mechanistic bridge between pump assemblies in different pathways.\n\nCellular localization follows from both the membrane-anchored architecture and pump biology. The protein is annotated as a single-pass membrane component and is positioned at the cell surface, which matches GO:0005886 plasma membrane. A single transmembrane helix typically tethers regulatory scaffolds to the membrane while exposing interaction surfaces to the cytosol; this arrangement situates the protein at the plasma membrane where Na+/K+-ATPase operates and where signaling assemblies form.\n\nIntegrating these lines, I propose a mechanism: a membrane-tethered ATPase-binding scaffold that modulates Na+/K+-ATPase activity and trafficking while also promoting V-ATPase assembly. By stabilizing pump complexes and coordinating their assembly and turnover, the protein can tune ion homeostasis and membrane excitability and, in parallel, support lysosomal acidification through V-ATPase biogenesis. Likely interaction partners include Na+/K+-ATPase alpha/beta subunits at the plasma membrane and cytosolic assembly factors for V-ATPase; transient contacts with trafficking adaptors would facilitate pump recycling and endo-lysosomal routing.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q4KMZ8.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q4KMZ8"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q4KMZ8/entry","atlas":"/p/Q4KMZ8"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}