{"uniprot":"A6NCF6","gene":"MAGEA13P","name":"Putative MAGE domain-containing protein MAGEA13P","organism":"Homo sapiens (Human)","status":"dark","length":341,"sequence":"MPHSQKSRHCELEQGLQAPKEAQGLVGVQVAEAEKVNTTASSSPSTLIQGTLEKVSASGTPGTPQSSQRVCSPCTTIKATPWNQSDESSRSQEKKDPGASQALMLEKKVDELVKFLSVKYTTKQPITEAEMLKGVIKEHKDHFPPIFMQAHECMEIVFGTDMKEVDPISHSCVLLKSLDLTYDRRLSDDQGMPKTGLLILTFGVILMEANCASEEKIWEVLNIIRVYAGWKDFIYGEPRKLITRDLVQEKYLECCQVSNSDPPRYKFPWGPRAHAETTKMKVLEFFSRVSGSDASSFPLLYEEALRDEKEKAQAIIATMGGTTLMASAHSWAKSSSFSCPE","function_summary":"A soluble human adaptor that shuttles between cytoplasm and nucleus to coordinate proteostasis and transcriptional repression. Its N-terminal regulatory segment and a bipartite winged-helix scaffold assemble multiprotein complexes that tune apoptosis pathways and gene expression. By organizing ubiquitin-system and chromatin-modifying assemblies, it promotes caspase activation and apoptotic competence while operating across cytoplasmic and nucleoplasmic compartments.","plain_language":"MAGEA13P has barely been studied. The model's best guess: A soluble human adaptor that shuttles between cytoplasm and nucleus to coordinate proteostasis and transcriptional repression. Its N-terminal regulatory segment and a bipartite winged-helix scaffold assemble multiprotein complexes that tune apoptosis pathways and gene expression.","uniprot_summary":"Involved in apoptosis and transcriptional repression.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0097202","label":"activation of cysteine-type endopeptidase activity"}],"cellular_component":[{"id":"GO:0005737","label":"cytoplasm"},{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR041898","name":"MAGE homology domain, winged helix WH1 motif","type":"homologous_superfamily","start":79,"end":186},{"id":"IPR041899","name":"MAGE homology domain, winged helix WH2 motif","type":"homologous_superfamily","start":189,"end":312},{"id":"IPR021072","name":"Melanoma associated antigen, N-terminal","type":"domain","start":3,"end":98},{"id":"IPR002190","name":"MAGE homology domain","type":"domain","start":105,"end":304},{"id":"IPR037445","name":"Melanoma-associated antigen","type":"family","start":4,"end":315}],"reasoning":"I begin with the InterPro architecture. The N-terminus carries IPR021072 (Melanoma associated antigen, N-terminal domain, residues 3–98), a hallmark module unique to this family that often mediates regulatory contacts and autoinhibition. Immediately downstream, the core of the protein is formed by IPR002190 (MAGE homology domain, residues 105–304), which is internally subdivided into two winged-helix-like elements: IPR041898 (MAGE homology domain, winged helix WH1 motif, residues 79–186) and IPR041899 (MAGE homology domain, winged helix WH2 motif, residues 189–312). This tandem WH1–WH2 arrangement creates a rigid, bipartite scaffold that binds partner proteins with high specificity and avidity. The entire polypeptide is encompassed by IPR037445 (Melanoma-associated antigen family, residues 4–315), reinforcing that this is a canonical MAGE-family adaptor. The ordered layout—an N-terminal regulatory segment feeding into a WH1/WH2-bearing MAGE homology core—causes multivalent protein-binding capacity rather than enzymatic chemistry, directly supporting GO:0005515 protein binding as the molecular function.\n\nA MAGE homology core typically recruits and modulates ubiquitin-system components and chromatin regulators. The WH1/WH2 scaffold provides the physical platform that assembles complexes controlling proteostasis and transcription. Such assemblies can tip cellular fate by coupling proteasome-directed pathways with stress-responsive transcription. This adaptor-driven control plausibly feeds into programmed cell death pathways that require caspase activation. In particular, scaffolding of proteostasis and transcriptional modules can facilitate the cascade that culminates in cysteine-type endopeptidase activation, aligning with GO:0097202 activation of cysteine-type endopeptidase activity. By stabilizing or exposing pro-caspase complexes and their activators, the architecture promotes the proteolytic cascade that defines apoptosis and related lytic programs.\n\nCellular localization follows from the same structural logic. The absence of transmembrane segments and the presence of soluble interaction modules argue for a non-membranous distribution. The N-terminal regulatory region and the MAGE core commonly shuttle between cytoplasm and nucleus to coordinate transcriptional repression and proteostasis. This supports a soluble intracellular residency split between GO:0005737 cytoplasm and GO:0005654 nucleoplasm. The experimentally observed cytoplasmic and nuclear pools are mechanistically explained by this modular scaffold that assembles complexes in both compartments.\n\nMechanistically, I hypothesize that the N-terminal domain tunes assembly and subcellular partitioning, while the WH1/WH2-bearing MAGE core binds both chromatin-associated repressors and ubiquitin-system adaptors. In the cytoplasm, it likely engages E3 ligase assemblies and proteasome-associated factors to bias substrate selection and timing of caspase activation. In the nucleus, it likely associates with transcriptional repressors and histone-modifying enzymes to adjust expression of pro-apoptotic genes. Candidate partners include RING-type E3 ligases and their adaptors, chromatin repressors that silence target loci, and nuclear transport factors that mediate nucleocytoplasmic shuttling. Together, these interactions provide a coherent route from scaffolded binding (GO:0005515) to caspase activation (GO:0097202) within both cytoplasm and nucleoplasm (GO:0005737, GO:0005654).","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-A6NCF6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/A6NCF6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/A6NCF6/entry","atlas":"/p/A6NCF6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}