{"uniprot":"Q9H6Y5","gene":"MAGIX","name":"PDZ domain-containing protein MAGIX","organism":"Homo sapiens (Human)","status":"dark","length":334,"sequence":"MEPRTGDAADPRGSRGGRGPSPLAGPSARQLLARLDARPLAARAAVDVAALVRRAGATLRLRRKEAVSVLDSADIEVTDSRLPHATIVDHRPQHRWLETCNAPPQLIQGKARSAPKPSQASGHFSVELVRGYAGFGLTLGGGRDVAGDTPLAVRGLLKDGPAQRCGRLEVGDLVLHINGESTQGLTHAQAVERIRAGGPQLHLVIRRPLETHPGKPRGVGEPRKGVVPSWPDRSPDPGGPEVTGSRSSSTSLVQHPPSRTTLKKTRGSPEPSPEAAADGPTVSPPERRAEDPNDQIPGSPGPWLVPSEERLSRALGVRGAAQLAQEMAAGRRRH","function_summary":"A cytoplasmic PDZ-scaffold that assembles signaling complexes to dampen Ca2+-responsive pathways. By using a central PDZ module to capture partner proteins and organize them on intracellular organelle surfaces, it restrains calcineurin-driven activation of NFAT signaling. This adaptor-like role positions the protein at cytoplasmic interfaces of membrane-bounded compartments, where it spatially controls pathway assembly and reduces signaling throughput.","plain_language":"MAGIX has barely been studied. The model's best guess: A cytoplasmic PDZ-scaffold that assembles signaling complexes to dampen Ca2+-responsive pathways. By using a central PDZ module to capture partner proteins and organize them on intracellular organelle surfaces, it restrains calcineurin-driven activation of NFAT signaling.","uniprot_summary":"May be involved in intracellular signaling pathways.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0070885","label":"negative regulation of calcineurin-NFAT signaling cascade"}],"cellular_component":[{"id":"GO:0043231","label":"intracellular membrane-bounded organelle"}]},"interpro":[{"id":"IPR036034","name":"PDZ superfamily","type":"homologous_superfamily","start":113,"end":212},{"id":"IPR001478","name":"PDZ domain","type":"domain","start":125,"end":209},{"id":"IPR030031","name":"PDZ domain-containing protein MAGIX","type":"family","start":1,"end":334}],"reasoning":"I begin with the InterPro architecture. The sequence is annotated as IPR030031 (PDZ domain-containing protein MAGIX family) spanning residues 1–334, establishing a full-length family scaffold. Within this, a single PDZ module is clearly defined: IPR036034 (PDZ superfamily, residues 113–212) encompasses IPR001478 (PDZ domain, residues 125–209). This ordered layout—an N-to-C family envelope with a central PDZ domain—creates a canonical PDZ scaffold that recognizes short C-terminal PDZ-binding motifs on partner proteins. The solitary PDZ core and extended family region imply a modular adaptor that organizes multiprotein assemblies rather than catalyzing reactions. Such PDZ scaffolds cause multivalent protein association, directly supporting GO:0005515 protein binding as the molecular function.\n\nA PDZ scaffold typically dictates pathway topology by co-localizing receptors, channels, and signaling enzymes. The MAGIX-family envelope suggests specialization in intracellular signaling hubs. A central PDZ domain positioned mid-sequence enables simultaneous capture of membrane-proximal and cytosolic partners, which is well-suited to tune Ca2+-responsive pathways. By assembling or sequestering calcineurin and NFAT pathway components, a PDZ-centered adaptor can dampen calcineurin-dependent transcriptional responses. This mechanistic role aligns with GO:0070885 negative regulation of calcineurin-NFAT signaling cascade: the scaffold constrains pathway throughput by spatially restricting calcineurin/NFAT interactions and routing signals away from nuclear activation.\n\nCellular placement follows from the architecture and the stated localization. The absence of transmembrane segments and the presence of a soluble PDZ scaffold argue for a cytoplasmic protein that associates with membranes via partners. The localization to the cytoplasm and to intracellular membrane-bounded organelles (GO:0043231) is coherent: cytoplasmic pools feed into endoplasmic reticulum and Golgi-associated signaling platforms where Ca2+ flux and calcineurin activation are orchestrated. Thus, the PDZ scaffold operates at cytoplasmic surfaces of organelles to modulate downstream signaling.\n\nIntegrating these features yields a mechanistic hypothesis. The PDZ domain binds C-terminal motifs of membrane-proximal or cytosolic targets, assembling a supramolecular complex that tempers calcineurin/NFAT signaling. Likely partners include calcineurin catalytic/regulatory subunits and NFAT transcription factors, whose proximity and activation can be curtailed by scaffolded sequestration. Additional interactions with membrane-bounded organelle surfaces (ER/Golgi/endosomes) would position the complex near Ca2+ sources and trafficking routes. Consequently, the protein functions as a cytoplasmic PDZ adaptor that negatively regulates the calcineurin-NFAT cascade by spatially organizing pathway components and restricting their productive encounters.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9H6Y5.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9H6Y5"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9H6Y5/entry","atlas":"/p/Q9H6Y5"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}