Protein: Sterol-4-alpha-carboxylate 3-dehydrogenase erg26, decarboxylating (EC 1.1.1.170) (C-3 sterol dehydrogenase erg26) (C-4 decarboxylase erg26) (Ergosterol biosynthetic protein 26) (O43050)
Organism: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
Function: Sterol-4-alpha-carboxylate 3-dehydrogenase; part of the third module of ergosterol biosynthesis pathway that includes by the late steps of the pathway (By similarity). Erg26 is a catalytic component of the C-4 demethylation complex that catalyzes the oxidative decarboxylation that results in a reduction of the 3-beta-hydroxy group at the C-3 carbon to an oxo group (By similarity). The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase erg9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to form squalene, which is the precursor of all steroids. Secondly, squalene is converted into lanosterol by the consecutive action of the squalene epoxidase erg1 and the lanosterol synthase erg7. The lanosterol 14-alpha-demethylase erg11/cyp1 catalyzes C14-demethylation of lanosterol to produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol. In the next steps, a complex process involving various demethylation, reduction and desaturation reactions catalyzed by the C-14 reductase erg24 and the C-4 demethylation complex erg25-erg26-erg27 leads to the production of zymosterol. Erg28 likely functions in the C-4 demethylation complex reaction by tethering erg26 and Erg27 to the endoplasmic reticulum or to facilitate interaction between these proteins. Then, the sterol 24-C-methyltransferase erg6 catalyzes the methyl transfer from S-adenosyl-methionine to the C-24 of zymosterol to form fecosterol. The C-8 sterol isomerase erg2 catalyzes the reaction which results in unsaturation at C-7 in the B ring of sterols and thus converts fecosterol to episterol. The sterol-C5-desaturases erg31 and erg32 then catalyze the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol. The C-22 sterol desaturase erg5 further converts 5-dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double bond in the sterol side chain. Finally, ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28) sterol reductase erg4 to produce ergosterol (Probable). In the genus Schizosaccharomyces, a second route exists between lanosterol and fecosterol, via the methylation of lanosterol to eburicol by erg6, followed by C14-demethylation by erg11/cyp1 and C4-demethylation by the demethylation complex erg25-erg26-erg27 (Probable).
Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:16823372}; Peripheral membrane protein {ECO:0000269|PubMed:16823372}.
Sequence: MPMNSVLVIGSGFLGGHIIRQLCERENLRIAAFDLFENEKLLHELHGQFTMYTGDLTKQGDIERVFEEFHPRVVIHTASPVHNLARDIYFEVNVDGTANIIKACQKFNVDALVYTSSAGVVFNGADLINVDESQPIPEVHMDAYNESKALAEKQVLEASSESLKTAALRVAGLFGPGDRQLVPGMLSVLKNGQTKFQLGDNLNLFDFTYIENAAYAHLLAMDNLLSSNPTANGQVFFITNGQVIYFWDFARAIWAHAGHVPPYIIKFPRPVGMLLATAAEWVCYFLKKEPGFTRFRVQFSCANRYFNIQKAEDVLKYHPIVDLEEGIRRTLAWMDTEKKH
InterPro domains: - IPR002225: 3-beta hydroxysteroid dehydrogenase/isomerase (domain) [10-269]
- IPR036291: NAD(P)-binding domain superfamily (homologous_superfamily) [5-334]
- IPR050177: Bifunctional lipid A modification and metabolic enzymes (family) [3-334]
Interaction partners: - C-4 methylsterol oxidase erg25
- 3-keto-steroid reductase erg27
- Squalene synthase
- Lanosterol synthase erg7
- Lanosterol 14-alpha demethylase erg11
- Delta
- Sterol 24-C-methyltransferase erg6
- Ergosterol biosynthetic protein 28
- Squalene epoxidase erg1
- Delta
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0005515 (protein binding), GO:0016491 (oxidoreductase activity), GO:0016614 (oxidoreductase activity, acting on CH-OH group of donors), GO:0016616 (oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:1901615 (organic hydroxy compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0006629 (lipid metabolic process), GO:0044283 (small molecule biosynthetic process), GO:0044255 (cellular lipid metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006066 (alcohol metabolic process), GO:0044107 (cellular alcohol metabolic process), GO:0016125 (sterol metabolic process), GO:1902652 (secondary alcohol metabolic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0008204 (ergosterol metabolic process), GO:0008202 (steroid metabolic process), GO:0097384 (cellular lipid biosynthetic process), GO:1901617 (organic hydroxy compound biosynthetic process), GO:0044108 (cellular alcohol biosynthetic process), GO:0046165 (alcohol biosynthetic process), GO:0008610 (lipid biosynthetic process), GO:0016128 (phytosteroid metabolic process), GO:0006696 (ergosterol biosynthetic process), GO:0006694 (steroid biosynthetic process), GO:0016126 (sterol biosynthetic process), GO:0016129 (phytosteroid biosynthetic process), GO:1902653 (secondary alcohol biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0043229 (intracellular organelle), GO:0005783 (endoplasmic reticulum), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)