{"uniprot":"A0A096LP55","gene":"UQCRHL","name":"Cytochrome b-c1 complex subunit 6-like, mitochondrial","organism":"Homo sapiens (Human)","status":"dark","length":91,"sequence":"MGLEDEQKMLTESGDPEEEEEEEEELVDPLTTVREQCEQLEKCVKARERLELYDEHVSSRSHTEEDCTEELFDFLHAKDHCVAHKLFNNLK","function_summary":"A soluble, matrix-facing accessory subunit of mitochondrial complex III that forms the hinge scaffold of the cytochrome b–c1 assembly. By stabilizing and organizing the peripheral arm of the complex, it enables efficient electron transfer from ubiquinol to cytochrome c and supports the proton-coupled steps that drive oxidative phosphorylation. Its architecture and location position it at the inner-membrane–associated supercomplex surface, where it mediates multivalent contacts that maintain complex III integrity and tune catalytic output.","plain_language":"UQCRHL has barely been studied. The model's best guess: A soluble, matrix-facing accessory subunit of mitochondrial complex III that forms the hinge scaffold of the cytochrome b–c1 assembly. By stabilizing and organizing the peripheral arm of the complex, it enables efficient electron transfer from ubiquinol to cytochrome c and supports the proton-coupled steps that drive oxidative phosphorylation.","uniprot_summary":"Component of the ubiquinol-cytochrome c reductase complex (mitochondrial cytochrome b-c1 complex) that catalyzes the reduction of cytochrome c using electrons provided via ubiquinol. This complex couples electron transport to energy conservation by converting the energy of electron transport into a proton gradient.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"},{"id":"GO:0008121","label":"ubiquinol-cytochrome-c reductase activity"}],"biological_process":[{"id":"GO:0006119","label":"oxidative phosphorylation"}],"cellular_component":[{"id":"GO:0005750","label":"mitochondrial respiratory chain complex III"}]},"interpro":[{"id":"IPR036811","name":"Ubiquinol-cytochrome C reductase hinge domain superfamily","type":"homologous_superfamily","start":15,"end":91},{"id":"IPR023184","name":"Ubiquinol-cytochrome C reductase hinge domain","type":"domain","start":28,"end":91},{"id":"IPR003422","name":"Cytochrome b-c1 complex, subunit 6","type":"family","start":9,"end":91}],"reasoning":"I begin with the InterPro architecture. The polypeptide core is defined by IPR003422 (Cytochrome b-c1 complex, subunit 6 family) spanning residues 9–91, which identifies it as the soluble hinge subunit of mitochondrial complex III. Nested within this family signature is a conserved structural module: IPR036811 (Ubiquinol-cytochrome C reductase hinge domain superfamily) from residues 15–91 and the more specific IPR023184 (Ubiquinol-cytochrome C reductase hinge domain) from residues 28–91. The ordered layout—family-defining region covering nearly the entire chain with an internal hinge domain—indicates a single soluble domain that projects from the membrane-embedded core of complex III. This hinge architecture is known to create a flexible, acidic, matrix-facing arm that organizes and stabilizes the peripheral face of the cytochrome b-c1 assembly.\n\nThis domain composition dictates molecular function. The hinge domain lacks catalytic motifs for redox chemistry but is essential for assembling and tuning the electron-transfer machine that couples ubiquinol oxidation to cytochrome c reduction. By stabilizing inter-subunit contacts and positioning the peripheral arm, the hinge subunit enables the ensemble’s chemistry captured by GO:0008121 ubiquinol-cytochrome-c reductase activity. Its structural role also necessitates multivalent contacts with neighboring subunits and soluble partners, directly supporting GO:0005515 protein binding as a primary molecular function.\n\nFrom function to process, the hinge subunit’s scaffolding and allosteric effects propagate into the larger pathway of oxidative phosphorylation. By maintaining the integrity and dynamics of complex III, it ensures efficient electron flow from ubiquinol to cytochrome c, which is the central conduit of GO:0006119 oxidative phosphorylation. The hinge’s contribution to assembly and stability is causally upstream of electron transport and proton-motive coupling.\n\nCellular location follows from the hinge architecture and its role. The soluble hinge domain binds the matrix-exposed face of complex III, which is embedded in the mitochondrial inner membrane. Thus, the protein resides with GO:0005750 mitochondrial respiratory chain complex III and associates with the inner membrane environment inferred from its obligate complex III residency and soluble peripheral topology.\n\nMechanistically, the hinge domain forms a flexible scaffold that coordinates conformational states between cytochrome b and the soluble subunits, guiding the bifurcated electron transfer and proton-coupled steps of the Q cycle. By stabilizing the peripheral arm and modulating inter-subunit interfaces, it tunes electron bifurcation toward cytochrome c while supporting quinol oxidation and proton release. Likely interaction partners include the membrane core subunits and matrix/cytosolic-facing arms of complex III; transient contacts with cytochrome c and cardiolipin-rich membrane patches would further stabilize assembly and electron handoff.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-A0A096LP55.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/A0A096LP55"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/A0A096LP55/entry","atlas":"/p/A0A096LP55"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}