{"uniprot":"Q6NXP6","gene":"NOXRED1","name":"NADP-dependent oxidoreductase domain-containing protein 1","organism":"Homo sapiens (Human)","status":"dark","length":359,"sequence":"MDMLQDLESLQFEYGVPEEDRIWLYLQGRSRGLMIEACAHATFFCKLLYNLRASLNKNQSSRHLSIGSLNSATPEEFKVGIIGGGHLGKQLAGTLLQLGPIPAESLRISTRRPETLGELQKLGIKCFYHNADLVSWADVIFLCCLPSQLPNICVEIYTSLEKASIVYSFVAAIPLPRLKLLLNHTNILRPQYQYDEDSVSVWGANKGVIAALQDPTILQATCPYSPAGGIILNIKWLEGVFYAALNICTARNMAHSQVLQLLSELFLSVHFEDCGKDTASCPKLQLTDFVSKAYGKNLSQERPFPWFDLTAVQLKETPFSQHLSSSPVLQDHLTHLYCASFGISLTKEQPVISTGFPSQ","function_summary":"A soluble human oxidoreductase that uses a Rossmann-like dinucleotide-binding core to catalyze reversible reduction of pyrroline-5-carboxylate to proline in the cytosol. By coupling NAD(H)/NADP(H) chemistry to the proline metabolic node, it helps maintain cellular redox balance and osmoprotective capacity. Its soluble architecture supports dynamic protein associations that tune metabolic responses during calcium-triggered signaling pathways.","plain_language":"NOXRED1 has barely been studied. The model's best guess: A soluble human oxidoreductase that uses a Rossmann-like dinucleotide-binding core to catalyze reversible reduction of pyrroline-5-carboxylate to proline in the cytosol. By coupling NAD(H)/NADP(H) chemistry to the proline metabolic node, it helps maintain cellular redox balance and osmoprotective capacity.","uniprot_summary":"Catalyzes the reduction of pyrroline-5-carboxylate to L-proline.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0071277","label":"cellular response to calcium ion"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"}]},"interpro":[{"id":"IPR036291","name":"NAD(P)-binding domain superfamily","type":"homologous_superfamily","start":78,"end":185},{"id":"IPR028939","name":"Pyrroline-5-carboxylate reductase, catalytic, N-terminal","type":"domain","start":78,"end":170}],"reasoning":"I begin with the InterPro architecture. The polypeptide contains IPR036291 (NAD(P)-binding domain superfamily, residues 78–185), a Rossmann-like fold that creates a dinucleotide-binding cradle for NAD(H)/NADP(H). Nested within this region is IPR028939 (Pyrroline-5-carboxylate reductase, catalytic, N-terminal domain, residues 78–170), which specifies the enzyme class that reduces the cyclic imine intermediate of the proline pathway. The co-occurrence and overlap of a Rossmann-like NAD(P)-binding core with a P5C-reductase catalytic module establishes a soluble oxidoreductase that uses pyridine nucleotides to interconvert pyrroline-5-carboxylate and proline. This architecture causes two immediate functional consequences: first, a primary molecular role as an NAD(P)-dependent oxidoreductase; second, a propensity for multivalent protein binding that often accompanies soluble dehydrogenase/reductase assemblies.\n\nFrom this domain logic, I infer molecular function. The NAD(P)-binding superfamily (IPR036291) dictates cofactor usage and redox chemistry, while the P5C-reductase catalytic domain (IPR028939) defines substrate scope and reaction directionality. Together they produce a soluble enzyme that binds NAD(H)/NADP(H) and transient protein partners, aligning with GO:0005515 protein binding as a core molecular function. The absence of transmembrane segments or secretion signals further supports a soluble, cytosolic enzyme that forms dynamic complexes.\n\nConnecting function to process, the P5C-reductase chemistry feeds directly into proline metabolism and redox buffering. By driving the reversible reduction of pyrroline-5-carboxylate to L-proline, the enzyme modulates cellular responses to energetic and osmotic stress. Calcium-responsive pathways frequently couple cytoskeletal remodeling and metabolic state; a cytosolic redox enzyme that tunes the proline pool can therefore participate in the cellular response to calcium ion (GO:0071277) by adjusting downstream effectors and maintaining redox balance when calcium signaling intensifies.\n\nCellular location follows from the soluble Rossmann-fold architecture and the lack of targeting signals. The enzyme’s physicochemical properties and cytosolic catalytic role point to the cytosol (GO:0005829), consistent with a freely diffusing oxidoreductase that integrates metabolic cues with signaling pathways.\n\nMechanistically, I hypothesize that the enzyme operates as a cytosolic NAD(P)-dependent reductase that buffers the proline/P5C node. By binding NAD(H)/NADP(H) through its Rossmann-like core and engaging substrates via the P5C-reductase catalytic domain, it tunes proline accumulation and redox poise. This positioning predicts transient assemblies with other soluble metabolic enzymes and signaling adaptors. Likely partners include cytosolic proline-pathway enzymes and redox hubs that together coordinate calcium-evoked metabolic responses.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q6NXP6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q6NXP6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q6NXP6/entry","atlas":"/p/Q6NXP6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}