{"uniprot":"Q8N4K4","gene":"RPRML","name":"Reprimo-like protein","organism":"Homo sapiens (Human)","status":"dark","length":120,"sequence":"MNATFLNHSGLEEVDGVGGGAGAALGNRTHGLGTWLGCCPGGAPLAASDGVPAGLAPDERSLWVSRVAQIAVLCVLSLTVVFGVFFLGCNLLIKSESMINFLVQERRPSKDVGAAILGLY","function_summary":"A single-pass membrane-tethered regulator that uses a Reprimo-family scaffold to assemble protein complexes controlling cell-cycle progression. Its transmembrane anchor positions the protein on intracellular membranes while exposing cytosolic regions that mediate multivalent binding. By organizing checkpoint and apoptosis-linked assemblies at membrane surfaces, it modulates proliferative decisions and coordinates signaling between membrane trafficking and cell-cycle governance.","plain_language":"RPRML has barely been studied. The model's best guess: A single-pass membrane-tethered regulator that uses a Reprimo-family scaffold to assemble protein complexes controlling cell-cycle progression. Its transmembrane anchor positions the protein on intracellular membranes while exposing cytosolic regions that mediate multivalent binding.","uniprot_summary":"May be involved in the cell cycle regulation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0051726","label":"regulation of cell cycle"}],"cellular_component":[{"id":"GO:0005737","label":"cytoplasm"},{"id":"GO:0016021","label":"integral component of membrane"}]},"interpro":[{"id":"IPR060618","name":"Reprimo-like, transmembrane helix domain","type":"domain","start":60,"end":106},{"id":"IPR043383","name":"Reprimo family","type":"family","start":1,"end":120}],"reasoning":"I begin with the InterPro architecture. The sequence is encompassed by IPR043383 (Reprimo family, residues 1–120), marking it as a member of a cell-cycle–linked regulatory family. Within this scaffold sits IPR060618 (Reprimo-like, transmembrane helix domain, residues 60–106), a hydrophobic segment that forms a single-pass transmembrane anchor. This arrangement—an overall Reprimo-family framework coupled to a defined transmembrane helix—creates a membrane-tethered regulator whose soluble regions are poised for protein–protein interactions rather than catalysis. The absence of enzymatic motifs and the presence of a dedicated TM anchor together drive a binding-centric role, consistent with GO:0005515 protein binding as the molecular function.\n\nA membrane-anchored binding module typically exerts control by assembling or positioning regulatory complexes. The Reprimo-family signature is classically associated with cell-cycle governance; anchoring to membranes allows spatial control of checkpoints and apoptosis pathways that feed into proliferation decisions. This architecture therefore causes regulatory activity aligned with GO:0051726 regulation of cell cycle: membrane tethering concentrates signaling and checkpoint machinery, while cytosolic-facing regions recruit effectors that modulate cell-cycle transitions.\n\nThe transmembrane segment (60–106) dictates membrane association, and the experimentally supported single-pass topology places the protein as an integral membrane component. This supports GO:0005737 cytoplasm as a soluble compartment reached by its cytosolic-facing domains and also necessitates GO:0016021 integral component of membrane to capture its anchorage. The dual presence—membrane-embedded with cytoplasmic exposure—explains how it can both scaffold at a membrane and operate within cytoplasmic pathways.\n\nMechanistically, a plausible model is that the membrane anchor positions the protein at intracellular membranes (likely endoplasmic reticulum or endomembranes), where it nucleates complexes that couple membrane trafficking and stress signaling to cell-cycle control. The cytosolic regions would bind partners that enforce checkpoint and apoptotic circuits, thereby tuning proliferation. From this, I hypothesize interactions with cell-cycle effectors and checkpoint assemblies: cyclin-dependent kinase modules (e.g., CDK–cyclin complexes) and p53-pathway adaptors could be recruited transiently via the Reprimo-family interface. Additional contacts with membrane-associated scaffolds and trafficking regulators would stabilize the platform that restrains or advances cell-cycle progression depending on cellular stress and checkpoint status.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8N4K4.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8N4K4"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8N4K4/entry","atlas":"/p/Q8N4K4"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}