{"uniprot":"Q5T8A7","gene":"PPP1R26","name":"Protein phosphatase 1 regulatory subunit 26","organism":"Homo sapiens (Human)","status":"dark","length":1209,"sequence":"MFLMNASPVVALQSKWEAFGPPGSCRFPRCFSEADEGVESASVSARVQMLISTLQRDGAARGTSDERAAQRGHRAEGCHDARPAAKPTVHKEPPALAVCGLVADFDPMGEEETTDFGPLVLDSDSDDSVDRDIEEAIQEYLKAKSGAAQPGAGGAQPGAAQPSRAAGGGSRCKPEPAHGSAPTALCPPKLVPGSGGGPGSQVGSSKDQGSASPVSVSSDDSFEQSIRAEIEQFLNEKRQHETQKCDGSVEKKPDTNENSAKSLLKSHQEPPTKVVHRQGLLGVQKEFAFRKPPRLAKMNVQPRSLRSKVTTTQENEGSTKPATPCRPSEAAQNKGGIKRSASAARRGKRVMSAAQASEASDSSSDDGIEEAIQLYQLQKTRKEADGDLPQRVQLREERAPDPPAHSTSSATKSALPETHRKTPSKKKLVATKTMDPGPGGLDTDHAPKLLKETKAPPPASPASRSEFVERSSCRADTSAELMCAEAILDISKTILPAPVEGSDGSLSASPLFYSPNVPSRSDGDSSSVDSDDSIEQEIRTFLALKAQSGSLLARGESCPQAAQGPLLPPGLNSQTGGHKTPLSKTPDPLLGCKRKRRGGGHVRPSTPKKMQEVVKDGSQDADHSQGRAEPGHERRDLPIQGKASEALGGEGTARGPGDTRMSQGQGKTDEARRLDEKESSEDKSSSLDSDEDLDTAIKDLLRSKRKLKKRCREPRAACRKKVRFSTAQTHFLEQLGGLRRDWKDRGPPVLKSCLSKSKRDSGEGPGKKPPSVFGSTAERMRQEGAASQDAALAFRVRRPASASASEGNPFPRESQGPAPSPGSLSDDSSSVDSNDSIELEIRKFLAEKAKESVSSSEVQAEGPTALGTGGPARPEVLCRKEPAPPPGVCTRSQRARGVPHLAEGLRGTESAGAQGTAGLFSQGGKGLPAAPARGDPVPPRSTSGGVSAKGLSVSRRNVYVHKDQSPRGAEPAAKSAFGQLPSCATAGTEAGGARGTFHMGCGSPSFLTPSPGAERDAGAQADRTPPWSDFAHQSRLPSPWVLRSEGRDAVWRGGVGSERDKGSEGPARGLPSLPLAGFSPLLSTQLFHFGKGVSWGGRQAGLFSPHLGLPLQGPSFSAFREAQAGPSPVFGSPHLLAKKDGGPWPTRKAQAGLSLHDRRSSGSEESILDLRYRRRVNRDDQEQDALGSDASDFSDTSTEDSGGSSVVKV","function_summary":"A large human nuclear scaffold that assembles and directs a protein phosphatase complex to transcription machinery. By recruiting phosphatase components and positioning them on polymerase assemblies and associated chromatin factors, it promotes dephosphorylation cycles that transmit upstream signals to RNA polymerase pathways. This tuning of phosphorylation states supports RNA polymerase II– and III–driven transcription, including small nuclear RNA production, and operates predominantly within the nucleoplasm with soluble exchange that can involve cytosolic pools.","plain_language":"PPP1R26 has barely been studied. The model's best guess: A large human nuclear scaffold that assembles and directs a protein phosphatase complex to transcription machinery. By recruiting phosphatase components and positioning them on polymerase assemblies and associated chromatin factors, it promotes dephosphorylation cycles that transmit upstream signals to RNA polymerase pathways.","uniprot_summary":"Acts as a regulatory subunit for protein phosphatase 1.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0007165","label":"signal transduction"},{"id":"GO:0006366","label":"transcription by RNA polymerase II"},{"id":"GO:0006383","label":"transcription by RNA polymerase III"},{"id":"GO:0009301","label":"snRNA transcription"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"},{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR031474","name":"Protein phosphatase 1 regulatory subunit 26, N-terminal domain","type":"domain","start":1,"end":852},{"id":"IPR026130","name":"Protein phosphatase 1 regulatory subunit 26","type":"family","start":1,"end":1208}],"reasoning":"I begin with the InterPro architecture. The polypeptide carries IPR031474 (Protein phosphatase 1 regulatory subunit 26, N-terminal domain, residues 1–852), a large N-terminal module characteristic of PP1 regulatory subunits that mediates docking to the PP1 catalytic core and to substrates. This sits within a broader family signature, IPR026130 (Protein phosphatase 1 regulatory subunit 26 family, residues 1–1208), which spans essentially the full length and defines a non-catalytic scaffold specialized for assembling PP1 holoenzymes. The ordered layout—an extended N-terminal PP1-regulatory domain feeding into a long family-typical scaffold—causes multivalent protein binding rather than enzymatic chemistry, aligning with GO:0005515 protein binding as the primary molecular function.\n\nFrom this scaffolded PP1 regulatory architecture, I infer that the protein directs PP1 toward nuclear RNA polymerase assemblies. PP1 holoenzymes formed by such regulatory subunits dephosphorylate components of the transcription machinery and associated chromatin factors. This targeting explains participation in GO:0007165 signal transduction: phosphorylation/dephosphorylation cycles transmit upstream cues to transcriptional outputs. The same PP1-directed dephosphorylation modulates polymerase pathways, supporting GO:0006366 transcription by RNA polymerase II and GO:0006383 transcription by RNA polymerase III. A well-established axis is the snRNA and U6 pathways transcribed by RNA polymerase III; tuning their output via PP1-dependent dephosphorylation accounts for GO:0009301 snRNA transcription.\n\nCellular placement follows from function and sequence logic. PP1 regulatory subunits of this class operate in soluble nuclear environments where polymerase assemblies and chromatin remodelers reside. The absence of transmembrane features and the presence of nuclear transcriptional roles point to a soluble nuclear pool, specifically the GO:0005654 nucleoplasm. Dynamic exchange with soluble pools and assembly pathways can also place a fraction in the GO:0005829 cytosol, consistent with shuttling and assembly of PP1 complexes.\n\nMechanistically, the N-terminal IPR031474 domain recruits PP1 and positions it near core transcription modules. By concentrating PP1 on polymerase II/III and associated factors, the scaffold enforces dephosphorylation cycles that gate initiation and elongation, and that couple chromatin state to polymerase throughput. I hypothesize that the complex engages RNA polymerase II and III cores and their CTD-modifying systems, PP1-targeting subunits, and chromatin remodelers. Likely partners include PP1 catalytic subunits and their targeting modules, the CTD kinase/phosphatase axis, and snRNA/U6 transcription assemblies—together forming a nucleoplasmic PP1 holoenzyme that tunes transcriptional signaling and output.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q5T8A7.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q5T8A7"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q5T8A7/entry","atlas":"/p/Q5T8A7"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}