{"uniprot":"Q75LS8","gene":"FKBP9P1","name":"Putative FK506-binding protein 9-like protein","organism":"Homo sapiens (Human)","status":"dark","length":142,"sequence":"MDMGLREMCVGEKRTVIIPPHLGYGEAGVDGEVPGSAVLVFDIELLELVAGLPEGYMFIWNGEVSPNLFEEIDKDGNGEVLLEEFSEYIHAQVASGKGKLAPGFDAELIVKNMFTNQDRNGDGKVTAEEFKLKDQEAKQDEL","function_summary":"A soluble human protein that combines an FKBP-type isomerase core with a tandem EF-hand calcium sensor to coordinate calcium-dependent folding and assembly. By accelerating proline isomerization and using multivalent protein binding, it tunes the efficiency and directionality of translation, switching between enhancement and restraint according to calcium occupancy. Its soluble architecture supports pools in the cytosol and nucleoplasm, where it engages translation machinery and nuclear assemblies to couple ionic signals to protein assembly pathways.","plain_language":"FKBP9P1 has barely been studied. The model's best guess: A soluble human protein that combines an FKBP-type isomerase core with a tandem EF-hand calcium sensor to coordinate calcium-dependent folding and assembly. By accelerating proline isomerization and using multivalent protein binding, it tunes the efficiency and directionality of translation, switching between enhancement and restraint according to calcium occupancy.","uniprot_summary":"PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity).","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"},{"id":"GO:0005509","label":"calcium ion binding"}],"biological_process":[{"id":"GO:0017148","label":"negative regulation of translation"},{"id":"GO:0045727","label":"positive regulation of translation"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"},{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR046357","name":"Peptidyl-prolyl cis-trans isomerase domain superfamily","type":"homologous_superfamily","start":1,"end":51},{"id":"IPR011992","name":"EF-hand domain pair","type":"homologous_superfamily","start":57,"end":137},{"id":"IPR001179","name":"FKBP-type peptidyl-prolyl cis-trans isomerase domain","type":"domain","start":1,"end":49},{"id":"IPR002048","name":"EF-hand domain","type":"domain","start":60,"end":95},{"id":"IPR002048","name":"EF-hand domain","type":"domain","start":105,"end":140},{"id":"IPR051989","name":"FK506-binding protein-like isomerase","type":"family","start":1,"end":142},{"id":"IPR018247","name":"EF-Hand 1, calcium-binding site","type":"binding_site","start":118,"end":130}],"reasoning":"I begin with the domain architecture. The N-terminus (residues 1–49) carries IPR001179 (FKBP-type peptidyl-prolyl cis-trans isomerase domain), embedded within IPR046357 (Peptidyl-prolyl cis-trans isomerase domain superfamily, residues 1–51) and encompassed by IPR051989 (FK506-binding protein-like isomerase family, residues 1–142). This compact FKBP fold establishes a catalytic core that accelerates cis-trans isomerization of peptidyl-prolyl bonds, a reaction that remodels local protein structure and thereby tunes folding and assembly. Immediately following, the C-terminal half is dominated by calcium-sensing modules: IPR011992 (EF-hand domain pair, residues 57–137) comprises two EF-hand repeats, supported by IPR002048 (EF-hand domain, residues 60–95 and 105–140) and a defined Ca2+-coordinating site IPR018247 (EF-Hand 1, calcium-binding site, residues 118–130). The ordered layout—an N-terminal FKBP catalytic module followed by a tandem EF-hand Ca2+-sensor—creates a bifunctional architecture in which Ca2+ binding allosterically modulates the isomerase and scaffolding behavior.\n\nFrom this architecture, the molecular functions follow. The FKBP module causes peptidyl-prolyl isomerization and, together with its broad binding surface, supports GO:0005515 protein binding. The EF-hand pair and defined Ca2+-binding site directly impose GO:0005509 calcium ion binding. Calcium occupancy is expected to switch interaction modes and catalytic efficiency, coupling ionic signals to folding and assembly control.\n\nThese molecular activities propagate to biological processes. By accelerating proline isomerization and stabilizing assembly intermediates, the FKBP core promotes efficient ribosome-associated and cytosolic complex formation, which can enhance protein synthesis—captured by GO:0045727 positive regulation of translation. Conversely, the same chaperone-like surface can transiently sequester or misdirect assembly pathways, and together with Ca2+-dependent scaffolding, can attenuate ribosome throughput or mRNA engagement—captured by GO:0017148 negative regulation of translation. The dual-direction control is a natural outcome of a catalytic chaperone whose activity and binding are gated by Ca2+.\n\nCellular location is inferred from the soluble, non-membranous architecture and the need to access both cytoplasmic translation machinery and nuclear assemblies. The absence of transmembrane segments and the soluble FKBP/EF-hand composition point to a cytosolic pool, aligning with GO:0005829 cytosol. Dynamic shuttling and assembly roles also fit a nuclear-adjacent soluble fraction, supporting GO:0005654 nucleoplasm. This distribution enables rapid exchange between cytosolic translation control and nucleoplasmic complex assembly.\n\nMechanistically, the protein likely operates as a Ca2+-tuned folding catalyst and assembly hub. In the cytosol, Ca2+ binding to the EF-hand pair stabilizes conformations that favor interactions with translation factors and ribosome-associated complexes, toggling between enhancement and restraint of translational output. In the nucleoplasm, the same modularity supports assembly of nuclear protein complexes. I hypothesize transient interactions with ribosome-associated factors and translation regulators (e.g., eIFs and RNA-binding assemblies), as well as with other Ca2+-regulated chaperones and signaling adaptors. These partnerships would allow the FKBP catalytic core to couple proline isomerization and protein binding to calcium-driven control of assembly pathways in both cytosol and nucleoplasm.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q75LS8.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q75LS8"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q75LS8/entry","atlas":"/p/Q75LS8"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}