{"uniprot":"P55198","gene":"MLLT6","name":"Protein AF-17","organism":"Homo sapiens (Human)","status":"dark","length":1093,"sequence":"MKEMVGGCCVCSDERGWAENPLVYCDGHACSVAVHQACYGIVQVPTGPWFCRKCESQERAARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEEQGRESKAASGACMTCNRHGCRQAFHVTCAQMAGLLCEEEVLEVDNVKYCGYCKYHFSKMKTSRHSSGGGGGGAGGGGGSMGGGGSGFISGRRSRSASPSTQQEKHPTHHERGQKKSRKDKERLKQKHKKRPESPPSILTPPVVPTADKVSSSASSSSHHEASTQETSESSRESKGKKSSSHSLSHKGKKLSSGKGVSSFTSASSSSSSSSSSSGGPFQPAVSSLQSSPDFSAFPKLEQPEEDKYSKPTAPAPSAPPSPSAPEPPKADLFEQKVVFSGFGPIMRFSTTTSSSGRARAPSPGDYKSPHVTGSGASAGTHKRMPALSATPVPADETPETGLKEKKHKASKRSRHGPGRPKGSRNKEGTGGPAAPSLPSAQLAGFTATAASPFSGGSLVSSGLGGLSSRTFGPSGSLPSLSLESPLLGAGIYTSNKDPISHSGGMLRAVCSTPLSSSLLGPPGTSALPRLSRSPFTSTLPSSSASISTTQVFSLAGSTFSLPSTHIFGTPMGAVNPLLSQAESSHTEPDLEDCSFRCRGTSPQESLSSMSPISSLPALFDQTASAPCGGGQLDPAAPGTTNMEQLLEKQGDGEAGVNIVEMLKALHALQKENQRLQEQILSLTAKKERLQILNVQLSVPFPALPAALPAANGPVPGPYGLPPQAGSSDSLSTSKSPPGKSSLGLDNSLSTSSEDPHSGCPSRSSSSLSFHSTPPPLPLLQQSPATLPLALPGAPAPLPPQPQNGLGRAPGAAGLGAMPMAEGLLGGLAGSGGLPLNGLLGGLNGAAAPNPASLSQAGGAPTLQLPGCLNSLTEQQRHLLQQQEQQLQQLQQLLASPQLTPEHQTVVYQMIQQIQQKRELQRLQMAGGSQLPMASLLAGSSTPLLSAGTPGLLPTASAPPLLPAGALVAPSLGNNTSLMAAAAAAAAVAAAGGPPVLTAQTNPFLSLSGAEGSGGGPKGGTADKGASANQEKG","function_summary":"A nuclear chromatin reader that uses tandem PHD-type zinc-finger modules to bind histone tails and nucleosomes, thereby recruiting and positioning histone-modifying assemblies to regulate transcription. By anchoring to perinuclear and intranuclear chromatin, it scaffolds complexes that tune gene expression programs within the nucleoplasm and at the nuclear periphery, acting as a reader-driven organizer rather than a catalytic enzyme.","plain_language":"MLLT6 has barely been studied. The model's best guess: A nuclear chromatin reader that uses tandem PHD-type zinc-finger modules to bind histone tails and nucleosomes, thereby recruiting and positioning histone-modifying assemblies to regulate transcription. By anchoring to perinuclear and intranuclear chromatin, it scaffolds complexes that tune gene expression programs within the nucleoplasm and at the nuclear periphery, acting as a reader-driven organizer rather than a catalytic enzyme.","uniprot_summary":"May be involved in transcriptional regulation.","go_terms":{"molecular_function":[{"id":"GO:0031491","label":"nucleosome binding"},{"id":"GO:0042393","label":"histone binding"}],"biological_process":[{"id":"GO:0006355","label":"regulation of DNA-templated transcription"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"},{"id":"GO:0031965","label":"nuclear membrane"}]},"interpro":[{"id":"IPR013083","name":"Zinc finger, RING/FYVE/PHD-type","type":"homologous_superfamily","start":2,"end":60},{"id":"IPR011011","name":"Zinc finger, FYVE/PHD-type","type":"homologous_superfamily","start":7,"end":71},{"id":"IPR013083","name":"Zinc finger, RING/FYVE/PHD-type","type":"homologous_superfamily","start":61,"end":182},{"id":"IPR019787","name":"Zinc finger, PHD-finger","type":"domain","start":5,"end":57},{"id":"IPR001965","name":"Zinc finger, PHD-type","type":"domain","start":7,"end":55},{"id":"IPR049781","name":"AF-10/AF-17, PHD finger","type":"domain","start":7,"end":54},{"id":"IPR034732","name":"Extended PHD (ePHD) domain","type":"domain","start":62,"end":181},{"id":"IPR019787","name":"Zinc finger, PHD-finger","type":"domain","start":117,"end":180},{"id":"IPR001965","name":"Zinc finger, PHD-type","type":"domain","start":119,"end":178},{"id":"IPR050701","name":"Histone Modification Regulator","type":"family","start":8,"end":453},{"id":"IPR019786","name":"Zinc finger, PHD-type, conserved site","type":"conserved_site","start":8,"end":54}],"reasoning":"I begin by dissecting the InterPro architecture and its order along the sequence. The N-terminus is densely packed with PHD-type zinc-finger signatures: IPR013083 (Zinc finger, RING/FYVE/PHD-type homologous_superfamily, residues 2–60) and IPR011011 (Zinc finger, FYVE/PHD-type homologous_superfamily, residues 7–71) frame an early PHD core that is refined by multiple PHD-specific calls. The first PHD block is defined by IPR019787 (Zinc finger, PHD-finger domain, residues 5–57), IPR001965 (Zinc finger, PHD-type domain, residues 7–55), and IPR049781 (AF-10/AF-17, PHD finger domain, residues 7–54), together specifying a canonical histone-reader module tuned to AF-10/AF-17 family determinants. This N-terminal PHD cluster is followed by a second, extended PHD region: IPR034732 (Extended PHD, ePHD domain, residues 62–181) and a downstream PHD block captured by IPR019787 (Zinc finger, PHD-finger domain, residues 117–180) and IPR001965 (Zinc finger, PHD-type domain, residues 119–178). The tandem arrangement—an N-terminal canonical PHD followed by an extended PHD—creates a bivalent chromatin-recognition platform that stabilizes nucleosome engagement and histone-tail binding. The entire N-to-mid region is encompassed by IPR013083 (Zinc finger, RING/FYVE/PHD-type homologous_superfamily, residues 61–182), reinforcing a chromatin-reader architecture rather than an enzymatic core. Finally, IPR050701 (Histone Modification Regulator family, residues 8–453) spans most of the polypeptide, indicating a scaffold that organizes histone-modifying assemblies.\n\nThis dual-PHD/ePHD architecture causes high-affinity chromatin association and histone-tail recognition, which directly supports GO:0031491 nucleosome binding and GO:0042393 histone binding as the molecular functions. The absence of catalytic motifs and the presence of multiple reader domains argue that the protein operates by recruiting and positioning histone-modifying complexes rather than catalyzing modifications itself.\n\nFrom these binding activities, the biological role follows: by docking onto nucleosomes and histone tails, the protein modulates transcriptional outputs through chromatin state transitions. This reader-driven assembly and positioning of histone-modifying machineries mechanistically underpins GO:0006355 regulation of DNA-templated transcription. The AF-10/AF-17-tuned PHD finger suggests coupling to transcriptional elongation and chromatin remodeling pathways, consistent with a regulator that gates access to gene expression programs.\n\nCellular localization is dictated by chromatin engagement and nuclear architecture. The PHD-centered reader system anchors the protein in the nuclear interior, aligning with GO:0005654 nucleoplasm. The architecture and function also rationalize proximity to the nuclear periphery; chromatin domains often tether to the inner nuclear membrane, providing a basis for GO:0031965 nuclear membrane association via perinuclear chromatin hubs.\n\nMechanistically, the tandem PHD/ePHD platform recruits histone-modifying assemblies to specific genomic loci, where it can stabilize complexes that deposit or interpret histone marks. I hypothesize that it nucleates assemblies with histone methyltransferases and elongation-coupled factors, positioning them on nucleosomes to fine-tune transcriptional output. Likely partners include histone-modifying complexes and elongation-coupled adaptors that recognize and propagate chromatin states. Through these interactions, the protein acts as a nuclear scaffold that reads histone codes and channels them into regulated transcriptional programs.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-P55198.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/P55198"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/P55198/entry","atlas":"/p/P55198"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}