NCP1 (YHR042W, P16603) review notes
Identity
- NADPH--cytochrome P450 reductase (CPR), EC 1.6.2.4, diflavin (FAD + FMN) reductase; synonyms CPR1, PRD1 [UniProt:P16603].
- Single-pass membrane protein anchored by an N-terminal segment, catalytic domain on the cytoplasmic side; ER membrane is the main location; also detected in mitochondrial outer membrane proteomes and isolated plasma membranes [UniProt:P16603].
Activity
- Purified recombinant native and N-terminally truncated CPR reduce cytochrome c and reconstitute CYP61 (Erg5) sterol Delta22-desaturation PMID:11485306.
- CYP51-CPR fusion is catalytically active with NADPH PMID:9087488.
- Catalyses NADPH-dependent ferrireductase activity of isolated plasma membranes, but not essential for cellular ferrireductase activity PMID:9368374.
- In vitro, Ncp1/NADPH can reduce Dph3 and support the first step of diphthamide synthesis, slower than Cbr1 (physiological relevance unclear) PMID:27694803.
Ergosterol biosynthesis role
- ncp1 disruption is viable, ~25% ergosterol PMID:9468503; electron donor to squalene epoxidase (Erg1), CYP51 (Erg11) and CYP61 (Erg5) PMID:9468503.
- Deletion makes cells 200-fold more ketoconazole sensitive; an alternative electron supply exists PMID:2543395; the alternative is cytochrome b5 (CYB5), a multicopy suppressor PMID:8181746.
Curation conclusions
- Core MF GO:0003958 NADPH-hemoprotein reductase activity; BP GO:0006696; CC GO:0005789 ER membrane.
- IBA "cytosol" from a diflavin-reductase node that includes NOS, MTRR, NDOR1/TAH18 does not fit the membrane-anchored CPR: removed.
- Mitochondrial outer membrane / plasma membrane detections kept as non-core.
- YeastCyc lists the reductase only as a generic reactant of the ERG1/ERG11/ERG5 reactions; the module adds NCP1 explicitly.