{"uniprot":"Q6ZMV5","gene":"PPP4R3C","name":"Protein PPP4R3C","organism":"Homo sapiens (Human)","status":"dark","length":832,"sequence":"MAGLRYSVKVYVLNEDEEWNNLGTGQVSSTYDEQFQGMSLLVRSDSDGSVILRSQIPPDRPYGKYQETLIVWYEAENQGLVLKFQDPAGCQDIWKEICQAQGKDPSIQTTVNISDEPEEDFNEMSVISNMVVLPDCELNTLDQIADIVTSVFSSPVTDRERLAEILKNEAYIPKLLQLFHTCENLENTEGLHHLYEIIKGILFLNEACLFEIMFSDECIMDVVGCLEYDPALDQPKRHRDFLTNDAKFKEVIPITNSELRQKIHQTYRLQYIYDILLPVPSIFEDNFLSTLTTFIFSNKAEIVSMLQKDHKFLYEVFAQLKDETTHDDRRCELLFFFKELCSFSQALQPQSKDALFETLIQLGVLPALKIVMIRDDLQVRSAAAVICAYLVEYSPSRIREFIISEAHVCKDSDLFINVIIKQMICDTDPELGGAVHLMVVLHTLLDPRNMLTTPEKSERSEFLHFFYKHCMHKFTAPLLAATSEHNCEEDDIAGYDKSKNCPNDNQTAQLLALILELLTFCIQHHTFYIRSYILNKDLLRKALILMNSKHTHLILCVLRFMRRMICLNDEAYNNYIIKGNLFEPVVNALLDNGTRYNMLNSAILELFEYIRVENIKPLVSHIVEKFYNTLESIEYVQTFKGLKIKYEKERDRQSQIQKNLHSVLQNIVVFRGTIEEIGLEEEICFMEDAGEVVMPPLEDDDEFMETKRTQEGEAVMPPLEDDDKFTETKRTHQEGEAVMPPLEDDDEFMETKRNQEHEGKVDSPKRTSSGDFKFSSSYSACAAIGTGSPSGSSVVRLVDHPDDEEEKEEDEEEKEEDKEDETSPKKKPHLSS","function_summary":"A non-catalytic regulatory subunit that assembles and targets a serine/threonine phosphatase complex to chromatin and RNA-processing hubs. Its N-terminal ligand-capture module and central armadillo-type scaffold organize the phosphatase core and its substrates, directing dephosphorylation events that tune genome maintenance and transcriptional programs. By concentrating within nuclear speckles and on chromatin, and by transiently associating with the centrosome, it modulates pathways that resolve DNA double-strand breaks and coordinates broader regulatory functions of the phosphatase.","plain_language":"PPP4R3C has barely been studied. The model's best guess: A non-catalytic regulatory subunit that assembles and targets a serine/threonine phosphatase complex to chromatin and RNA-processing hubs. Its N-terminal ligand-capture module and central armadillo-type scaffold organize the phosphatase core and its substrates, directing dephosphorylation events that tune genome maintenance and transcriptional programs.","uniprot_summary":"Regulatory subunit of serine/threonine-protein phosphatase 4 (PP4).","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006282","label":"regulation of DNA repair"},{"id":"GO:2000779","label":"regulation of double-strand break repair"}],"cellular_component":[{"id":"GO:0000785","label":"chromatin"},{"id":"GO:0016607","label":"nuclear speck"},{"id":"GO:0005813","label":"centrosome"},{"id":"GO:0008287","label":"protein serine/threonine phosphatase complex"}]},"interpro":[{"id":"IPR011993","name":"PH-like domain superfamily","type":"homologous_superfamily","start":5,"end":122},{"id":"IPR016024","name":"Armadillo-type fold","type":"homologous_superfamily","start":172,"end":635},{"id":"IPR055236","name":"PP4R3, EVH1-like domain","type":"domain","start":6,"end":103},{"id":"IPR006887","name":"Serine/threonine-protein phosphatase 4 regulatory subunit 3-like, central domain","type":"domain","start":143,"end":647},{"id":"IPR051137","name":"Serine/threonine-protein phosphatase 4 regulatory subunit 3-like","type":"family","start":7,"end":798}],"reasoning":"I begin with the InterPro architecture. The N-terminus carries IPR011993 (PH-like domain superfamily, residues 5–122) that overlaps with IPR055236 (PP4R3, EVH1-like domain, residues 6–103). EVH1-like modules are PH-fold derivatives that create peptide-binding grooves specialized for docking proline-rich or low-complexity ligands; this fold dictates selective protein recruitment rather than catalysis. The central body of the protein is defined by IPR016024 (Armadillo-type fold, residues 172–635), a tandem-repeat scaffold that generates extended surfaces for multivalent assembly. This repeat-rich core is embedded within IPR006887 (Serine/threonine-protein phosphatase 4 regulatory subunit 3-like, central domain, residues 143–647), and the entire polypeptide is classified by IPR051137 (Serine/threonine-protein phosphatase 4 regulatory subunit 3-like family, residues 7–798). The ordered layout—an N-terminal EVH1-like capture module feeding into a large armadillo-type scaffold within a PP4R3 central domain—creates a high-affinity, non-enzymatic platform that organizes the PP4 catalytic core and its substrates. This architecture causes robust protein-binding capacity and positions the regulator to tune PP4 activity and targeting, consistent with GO:0005515 protein binding as the molecular function.\n\nFrom this scaffolded PP4R3 framework, I infer biological roles that require precise dephosphorylation control. The EVH1-like and armadillo-type assemblies are ideal for assembling chromatin-associated complexes and RNA-processing hubs. Such assemblies naturally govern pathways that resolve DNA lesions and coordinate repair factor dynamics. This mechanistic role aligns with regulation of DNA repair and specifically with regulation of double-strand break repair (GO:0006282 and GO:2000779). The PP4R3 scaffold can recruit chromatin remodelers and checkpoint factors, thereby modulating phosphorylation states that gate repair pathway choice and completion.\n\nCellular localization follows directly from the binding architecture and known assemblies. The EVH1-like capture and armadillo scaffold favor stable incorporation into the PP4 holoenzyme, supporting residence in the protein serine/threonine phosphatase complex (GO:0008287). The propensity to assemble chromatin-bound assemblies explains presence on chromatin (GO:0000785) and concentration within nuclear speckles (GO:0016607), where RNA processing and DNA repair signaling intersect. The same modular scaffold can target pericentriolar assemblies, rationalizing localization at the centrosome (GO:0005813), where PP4-dependent dephosphorylation coordinates cell-cycle and cytoskeletal interfaces.\n\nMechanistically, I propose that the N-terminal EVH1-like domain captures specific ligands and adaptors, while the armadillo core stabilizes higher-order assemblies that dock the PP4 catalytic subunit and its accessory partners. This causes selective dephosphorylation of chromatin and RNA-processing substrates, thereby tuning DNA repair pathways and transcriptional responses. Likely interaction partners include the PP4 catalytic core and chromatin/RNA-processing factors concentrated in nuclear speckles and on chromatin; centrosomal adaptors may mediate cell-cycle-linked targeting. Together, these features define a non-catalytic regulator that targets PP4 to nuclear and centrosomal substrates to control genome maintenance and transcriptional programs.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q6ZMV5.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q6ZMV5"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q6ZMV5/entry","atlas":"/p/Q6ZMV5"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}