{"uniprot":"Q8N7X1","gene":"RBMXL3","name":"RNA-binding motif protein, X-linked-like-3","organism":"Homo sapiens (Human)","status":"dark","length":1067,"sequence":"MMEADRPEKLFIGGLNLKTDEKALKAEFGKYGHIIKVFLMKDRKTNKSRGFAFVTFESPADAKAAARDMNGKYLDGKAIMVAQTIKPAFKSSRWVPPTPGSGSRSRFSHRTRGGGSSPQRPPSQGRPDDGRGYAGYFDLWPYRAPMPRKRGPPPRHWASPPHKRATPSSLAHSVGCGMRGKAPTVSGQDGYSGLQPRRWAGPPHKRAVPRSSLARIGGSGMPGKAPAVWGQDGYSGPRVREPLPPCRDPGDFVPALRDYSRRYYGHSSVPDYRPLRGDGNQNGYRGRDHEYTDHPSKGSYREPLKSYGGPCGAAPVWGTPPSYGGGCRYEEYQGNSPDACSEGRSSEALPVVLPDAYSRDHSPKAYSGGRSSSSNGYSRSDRYGEEGCYEEYRGRSPDAHSGGRNSSSNSYGQSHHYGGEGRYEEYRGRSHEARSGGRSTDAHSRGRSDDAYSGGHDSSSWSDCCGGGGRYEEYQGRSLDANSGGCSPEAYSGGHDNSSWSDRYGVGGHYEENRGHSLDANSGGRSPDTHSGGHSSSSNSYGQSHRYGGEGRYEYRGRSHDAHSGGCSADAYSGGHDSSSQSNRYGGGGCYEEYRGRSLDANSGGRSPNAYSGGHDSSSWSHRYGGGGRYEEYRGRSLDANSGGRSPDAYSGGHDSSGQSNCYGGGGRYEEYRGRLLDANSGGRSPDAYSGGHDSSSQSNRYGGGGRYEEYRGHSLDANSGGRSPDTYSRGHDSSSQSDHYGGGGRSLDANSSGRLPDAYSGGHDSSSRSHRYGGGGRYEEYRGRSLDANSGGRSPNAYSGGHNSSSRNDPCRGGGRYEENRGHSLDANSGGHSPNAYSGGRDSSSNSYDRSHRYGGGGHYEEYRGRSHDTHSRGRSPDAHSGDHYTEAYSRGRDSFSNSYGRSDHYGRGGCYEEYQGRSPNAYGGGRGLNSSNNSHGRSHRYGGGGRYEEYRGPSPDAHSGGRDSSIKSYGLSDRYGGGGHYEEYQGSLPDAYSGDHDRSSNSYGRSDRYSRGRDRVGRPDRGLPLPMETGSPPLHDSYSRSGCRVPRGGGRQGGRFERGEGRSRY","function_summary":"A nuclear RNA-binding regulator that assembles on pre-mRNA through an RRM-centered platform to control alternative splicing and mRNA fate. By engaging pre-mRNA and recruiting spliceosomal factors in the nucleoplasm and nucleolus, it modulates exon choice and thereby shapes differentiation programs, including those of keratinocytes. Its mechanism relies on high-affinity RNA recognition coupled to multivalent protein interactions that stabilize spliceosome-associated ribonucleoprotein assemblies.","plain_language":"RBMXL3 has barely been studied. The model's best guess: A nuclear RNA-binding regulator that assembles on pre-mRNA through an RRM-centered platform to control alternative splicing and mRNA fate. By engaging pre-mRNA and recruiting spliceosomal factors in the nucleoplasm and nucleolus, it modulates exon choice and thereby shapes differentiation programs, including those of keratinocytes.","uniprot_summary":"RNA-binding protein that is involved in pre-mRNA splicing.","go_terms":{"molecular_function":[{"id":"GO:0003729","label":"mRNA binding"},{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0000381","label":"regulation of alternative mRNA splicing, via spliceosome"},{"id":"GO:0030216","label":"keratinocyte differentiation"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"},{"id":"GO:0005730","label":"nucleolus"}]},"interpro":[{"id":"IPR012677","name":"Nucleotide-binding alpha-beta plait domain superfamily","type":"homologous_superfamily","start":2,"end":137},{"id":"IPR035979","name":"RNA-binding domain superfamily","type":"homologous_superfamily","start":9,"end":115},{"id":"IPR000504","name":"RNA recognition motif domain","type":"domain","start":8,"end":86},{"id":"IPR050441","name":"RNA-binding motif","type":"family","start":3,"end":306}],"reasoning":"I begin with the InterPro architecture. The N-terminus houses IPR012677 (Nucleotide-binding alpha-beta plait domain superfamily, residues 2–137), a structural scaffold that frequently supports nucleic acid–binding folds. Nested within this region is IPR035979 (RNA-binding domain superfamily, residues 9–115), and centrally embedded is IPR000504 (RNA recognition motif domain, residues 8–86). This canonical RRM core is followed and extended by IPR050441 (RNA-binding motif family, residues 3–306), which spans nearly the full length and indicates an extended RNA-binding platform beyond the classical RRM. The ordered layout—an N-terminal alpha-beta plait supporting an RRM core that is further extended by additional RNA-binding family features—creates a high-affinity, sequence-selective RNA-binding module. This architecture causes direct mRNA engagement and multivalent protein contacts typical of splicing regulators.\n\nFrom this domain logic, the molecular function resolves into two complementary activities. First, the RRM-centered module confers GO:0003729 mRNA binding by directly recognizing single-stranded regions of pre-mRNA and mRNA. Second, the extended RNA-binding family signature and exposed beta-sheet surfaces promote assembly with other ribonucleoprotein factors, supporting GO:0005515 protein binding. Together, these features equip the protein to dock onto pre-mRNA while recruiting or stabilizing spliceosomal components.\n\nThese molecular activities drive specific biological processes. By binding pre-mRNA and organizing spliceosomal assemblies, the protein regulates splice-site choice, aligning with GO:0000381 regulation of alternative mRNA splicing, via spliceosome. Its splicing control cascades into tissue-specific programs; modulation of keratin and signaling transcripts provides a mechanistic route into GO:0030216 keratinocyte differentiation, where alternative splicing patterns steer epidermal lineage decisions.\n\nCellular localization follows from function and architecture. Splicing regulation occurs in the nuclear interior, particularly in the GO:0005654 nucleoplasm where spliceosome assembly and catalysis take place. The presence of nucleic acid–binding folds and splicing roles also rationalizes transient residence in the GO:0005730 nucleolus, a hub for RNP biogenesis and RNA-processing factor storage/assembly. The soluble, non-membranous architecture and absence of transmembrane features reinforce a nuclear, nucleoplasmic working site with nucleolar shuttling.\n\nMechanistically, the RRM core binds pre-mRNA near regulated exons/introns, while the extended RNA-binding platform stabilizes spliceosomal components to bias exon inclusion/skipping. I hypothesize that it forms ribonucleoprotein assemblies with SR proteins and hnRNPs to fine-tune exon choice. Likely partners include U2AF heterodimer components and SF3 complexes that define the branchpoint and E/A complexes, as well as keratinocyte-enriched RNA-binding factors that couple splicing to differentiation cues. This cooperative assembly provides the specificity and regulatory leverage required for alternative splicing and downstream epidermal differentiation programs.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8N7X1.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8N7X1"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8N7X1/entry","atlas":"/p/Q8N7X1"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}