{"uniprot":"Q9H6N6","gene":"MYH16","name":"Putative uncharacterized protein MYH16","organism":"Homo sapiens (Human)","status":"dark","length":1097,"sequence":"MGLKVIQQNVHKFLQLRFWGWWKLYNKVKPLLNVARQEEEMKAKEEELRKAMAQTQELVNKVKELEEKTATLSQEKNDLTIQLQAEQENLMDAEERLTWMMKTKMDLESQISDMRERLEEEEGMAASLSAAKRKLEGELSDLKRDLEGLETTLAKTEKEKQALDHKVRTLTGDLSLREDSITKLQKEKRALEELHQKTLDDLQAEEDKVNHLTKNNSKLSTQIHELEDNWEQEKKIRAEVEKARRKAESDLKMTIDNLNEMERSKLDLEEVVKKRDLEINSVNSKYEDEQSLNSTLQRKLKEHQDRIEELEEELEAERAMRAKIEQNRKREAELLKLRRELEEAALQSEATASTLRKKHVDSMAELTEHVESLQRVKSKLEKDKQVMKAEIDDLNASMETIQKSKMNAEAHVRKLEDSLSEANAKVAELERNQAEINAIRTRLQAENSELSREYEESQSRLNQILRIKTSLTSQVDDYKRQLDEESKSRSTAVVSLANTKHDLDLVKEQLEEEQGGKSELQRLVSKLNTEVTTWRTKYETDAIQRTEELEETKRKLAARLQEAEEAAETAQARAASLEKNKQRLQAEVEDLTIDLEKANAAAAALDKKQRLFDKMLAEWQQKCEELQVEVDSSQKECRMYMTESFKIKTAYEESLEHLESVKKENKTLQEEIKDLIDQLGEGGRSVHELQKLKKKLEMEKEELQVALEEAESSLEVEESKVIRIQLELAQVKADIDRRIHEKEEEFEATRKNHQRAIESLQASLEAEAKGRAEALRLKKKMETDLNEMEIQLDHANKNNSELVKTLKRLQQQIKDLQVQMDEDARQHEELRKQYNLQERRLSLLQTELEEVRSALEGSERSRKLLEQEVVEITEWHNEINIQNQSLLVVKRKLESDVQRISNEHEELISEFRLTEERAKKAMMDAARMAEELRQEQDHCMHLEKIKKNYEVTIKDLQAKMEEAEQLALKGGKRTIMKLEARIKELETELDGEQKQHVETVKTLCKNERRLKELVFQTEEDHKTNQRMQALVEKLQNKLKVYKRQIEEAEDQANQTLARYRKTVHELDDAEDRAGMAETALNKLRTRHRVAGKGITSV","function_summary":"A cytosolic myosin-tail scaffold that nucleates and stabilizes thick-filament assembly in striated muscle. Its elongated tail and clustered oligomerization modules create a multivalent platform that binds partner proteins to drive myosin filament assembly and maturation, thereby supporting sarcomeric architecture and force production during muscle contraction. It operates as a soluble assembly hub that transitions into the actin cytoskeleton as ordered filaments form.","plain_language":"MYH16 has barely been studied. The model's best guess: A cytosolic myosin-tail scaffold that nucleates and stabilizes thick-filament assembly in striated muscle. Its elongated tail and clustered oligomerization modules create a multivalent platform that binds partner proteins to drive myosin filament assembly and maturation, thereby supporting sarcomeric architecture and force production during muscle contraction.","uniprot_summary":"Plays a role in muscle contraction.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006941","label":"striated muscle contraction"},{"id":"GO:0031034","label":"myosin filament assembly"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"},{"id":"GO:0015629","label":"actin cytoskeleton"}]},"interpro":[{"id":"IPR014751","name":"DNA repair protein XRCC4-like, C-terminal","type":"homologous_superfamily","start":729,"end":782},{"id":"IPR014751","name":"DNA repair protein XRCC4-like, C-terminal","type":"homologous_superfamily","start":783,"end":827},{"id":"IPR014751","name":"DNA repair protein XRCC4-like, C-terminal","type":"homologous_superfamily","start":828,"end":878},{"id":"IPR014751","name":"DNA repair protein XRCC4-like, C-terminal","type":"homologous_superfamily","start":890,"end":935},{"id":"IPR002928","name":"Myosin tail","type":"domain","start":327,"end":1086}],"reasoning":"I begin with the InterPro architecture. A long IPR002928 Myosin tail domain spans residues 327–1086, establishing a coiled-coil scaffold that drives dimerization and higher-order filament assembly typical of myosin heavy-chain tails. Nested within the C-terminal half of this tail are four XRCC4-like C-terminal homologous-superfamily signatures: IPR014751 modules at 729–782, 783–827, 828–878, and 890–935. XRCC4-like folds are non-enzymatic, β-strand-rich oligomerization modules that stabilize large cytoskeletal assemblies. Their serial arrangement near the tail’s C-terminus creates a multivalent assembly platform that nucleates and stabilizes thick-filament architecture. The absence of catalytic motifs and the dominance of extended coiled-coil and XRCC4-like oligomerization domains causally enforce a role as a structural scaffold rather than an enzyme.\n\nThis architecture dictates the molecular function. The expansive myosin tail domain and XRCC4-like repeats generate multivalent interfaces that mediate avid protein-protein contacts, directly supporting GO:0005515 protein binding as the operative molecular function. The tail’s geometry and oligomerization propensity cause filament bundling and filament maturation.\n\nFrom this binding-driven scaffold function, the biological processes follow. By templating and stabilizing thick filaments, the protein directly executes GO:0031034 myosin filament assembly. Once assembly is achieved, the resulting thick filaments power sliding of myosin against actin, thereby driving GO:0006941 striated muscle contraction. The causal chain is: tail-mediated oligomerization and filament nucleation lead to ordered filament assembly, which in turn enables cooperative force generation in sarcomeres.\n\nCellular context is consistent with soluble assembly intermediates and final cytoskeletal incorporation. The soluble, non-membranous scaffold explains presence in GO:0005829 cytosol during pre-assembly and transport. Its ultimate destination and function—thick-filament formation and maintenance—are hallmarks of the GO:0015629 actin cytoskeleton. The XRCC4-like oligomerization modules further reinforce cytoskeletal residency by stabilizing filamentous assemblies.\n\nMechanistically, I hypothesize that the myosin tail domain forms a parallel coiled-coil dimer that recruits additional myosin tails via cooperative binding, while the clustered XRCC4-like segments clamp and align filament protofibrils. This assembly hub likely engages myosin-binding proteins and assembly chaperones to tune filament length and stability. Consequently, probable interaction partners include myosin heavy chains and light chains that dock onto the tail, myomesin-like filament stabilizers that cap or crosslink thick filaments, and assembly factors that chaperone filament maturation. Together, these interactions channel soluble precursors into a robust, contractile cytoskeletal network.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9H6N6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9H6N6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9H6N6/entry","atlas":"/p/Q9H6N6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}