CYB5 (YNL111C) encodes the major microsomal cytochrome b5 of S. cerevisiae, a small tail-anchored heme protein inserted in the endoplasmic reticulum membrane with its b5 heme domain facing the cytoplasm. It acts as a one-electron carrier that shuttles reducing equivalents (from NADH-cytochrome b5 reductase or NADPH-cytochrome P450 reductase) to membrane-bound oxygenases. In ergosterol biosynthesis it is required for efficient sterol C-4 demethylation by the C-4 methylsterol oxidase Erg25, and it can alone support the CYP51 (Erg11) 14alpha-demethylation reaction, which explains why cells lacking NCP1 still make ergosterol; multicopy CYB5 suppresses the azole hypersensitivity of ncp1 mutants. CYB5 is not essential when the P450 reductase is present.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: Genome-wide SWAT-GFP localisation to the ER (PMID:26928762). Consistent with the tail-anchored ER membrane topology of Cyb5. Reason: Correct, though ER membrane is more precise. Supporting Evidence: PMID:26928762 One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN001064421) for ER membrane, with yeast Cyb5 itself among the experimental descendants. Matches the tail-anchored microsomal b5. Reason: Core location; sound phylogenetic inference. Supporting Evidence: PMID:12514182 uniformly hydrophobic tail anchors are first inserted into the endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:12514182 Bipartite signals mediate subcellular targeting of tail-anch... | ACCEPT | Summary: Localisation study of tail-anchored proteins showing ER targeting (PMID:12514182). Cyb5 is a classical ER tail-anchored protein. Reason: Core location with experimental support. Supporting Evidence: PMID:12514182 uniformly hydrophobic tail anchors are first inserted into the endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0097) to ER membrane; correct. Reason: Core location. Supporting Evidence: file:yeast/CYB5/CYB5-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0008610 lipid biosynthetic process | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA machine-learning lipid biosynthetic process. True, as Cyb5 supplies electrons to sterol biosynthetic oxygenases, but the specific process (sterol biosynthesis) is separately annotated. Reason: Correct but general parent of the sterol biosynthesis annotation. Supporting Evidence: PMID:6163470 cytochrome b5 and a cyanide-sensitive enzyme are involved in the 4-demethylation of 4,4-dimethylzymosterol |
| GO:0009055 electron transfer activity | IDA PMID:10622712 Biodiversity of the P450 catalytic cycle: yeast cytochrome b... | ACCEPT | Summary: Purified yeast cytochrome b5 with NADH-cytochrome b5 reductase supplies both electrons for the CYP51 sterol 14alpha-demethylation reaction (PMID:10622712). This is the defining electron-carrier activity. Reason: Core MF, direct reconstitution evidence. Supporting Evidence: PMID:10622712 fungal CYP51 mediated sterol 14alpha-demethylation can be wholly and efficiently supported by the cytochrome b5/NADH cytochrome b5 reductase electron transport system |
| GO:0016126 sterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000451736, with Candida albicans CYB5 and yeast Cyb5) for sterol biosynthetic process. Consistent with the yeast and Candida data. Reason: Core BP; phylogenetically sound. Supporting Evidence: PMID:6163470 cytochrome b5 and a cyanide-sensitive enzyme are involved in the 4-demethylation of 4,4-dimethylzymosterol, but not the 14 alpha-demethylation of lanosterol, by yeast microsomes |
| GO:0016126 sterol biosynthetic process | IDA PMID:10622712 Biodiversity of the P450 catalytic cycle: yeast cytochrome b... | ACCEPT | Summary: Reconstitution of CYP51 sterol demethylation with yeast Cyb5 and b5 reductase (PMID:10622712) supports direct participation in sterol biosynthesis as electron donor. Reason: Core BP; Cyb5 does work in the process by reducing the sterol oxygenases. Supporting Evidence: PMID:10622712 can account for the continued ergosterol production seen in yeast strains containing a disruption of the gene encoding CPR |
| GO:0020037 heme binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA heme binding for the cytochrome b5 family; Cyb5 is a b-type hemoprotein. Reason: Correct; the heme is the redox centre of the electron carrier. Supporting Evidence: file:yeast/CYB5/CYB5-uniprot.txt Membrane bound hemoprotein which function as an electron |
| GO:0020037 heme binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro cytochrome b5 heme-binding domain (IPR018506) mapping; correct. Reason: Correct. Supporting Evidence: file:yeast/CYB5/CYB5-uniprot.txt Membrane bound hemoprotein which function as an electron |
Loading supporting content…
Download this section (compressed HTML)Q: Is free Cyb5 required for Erg3 C-5 desaturation and for Ole1 fatty acid desaturation in vivo, given that Ole1 and Scs7 carry fused b5 domains?
Experiment: Profile sterols and fatty acids in cyb5, cyb5 ncp1 (with sterol supplementation) and cyb5 ole1-b5-domain mutants to assign which oxygenases depend on free Cyb5 in vivo.
Cytochrome b5; involved in the sterol and lipid biosynthesis pathways; acts as an electron donor to support sterol C5-6 desaturation
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)