ERG26_SCHPO
ID ERG26_SCHPO Reviewed; 340 AA.
AC O43050;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Sterol-4-alpha-carboxylate 3-dehydrogenase erg26, decarboxylating {ECO:0000250|UniProtKB:P53199};
DE EC=1.1.1.170 {ECO:0000250|UniProtKB:P53199};
DE AltName: Full=C-3 sterol dehydrogenase erg26 {ECO:0000250|UniProtKB:P53199};
DE AltName: Full=C-4 decarboxylase erg26 {ECO:0000250|UniProtKB:P53199};
DE AltName: Full=Ergosterol biosynthetic protein 26 {ECO:0000250|UniProtKB:P53199};
GN Name=erg26 {ECO:0000250|UniProtKB:P53199}; ORFNames=SPBC3F6.02c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP FUNCTION.
RX PubMed=8586261; DOI=10.1111/j.1574-6968.1995.tb07929.x;
RA Harmouch N., Coulon J., Bonaly R.;
RT "Identification of 24-methylene-24,25-dihydrolanosterol as a precursor of
RT ergosterol in the yeasts Schizosaccharomyces pombe and Schizosaccharomyces
RT octosporus.";
RL FEMS Microbiol. Lett. 134:147-152(1995).
RN [3]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [4]
RP FUNCTION.
RX PubMed=18310029; DOI=10.1099/mic.0.2007/011155-0;
RA Iwaki T., Iefuji H., Hiraga Y., Hosomi A., Morita T., Giga-Hama Y.,
RA Takegawa K.;
RT "Multiple functions of ergosterol in the fission yeast Schizosaccharomyces
RT pombe.";
RL Microbiology 154:830-841(2008).
CC -!- FUNCTION: Sterol-4-alpha-carboxylate 3-dehydrogenase; part of the third
CC module of ergosterol biosynthesis pathway that includes by the late
CC steps of the pathway (By similarity). Erg26 is a catalytic component of
CC the C-4 demethylation complex that catalyzes the oxidative
CC decarboxylation that results in a reduction of the 3-beta-hydroxy group
CC at the C-3 carbon to an oxo group (By similarity). The third module or
CC late pathway involves the ergosterol synthesis itself through
CC consecutive reactions that mainly occur in the endoplasmic reticulum
CC (ER) membrane. Firstly, the squalene synthase erg9 catalyzes the
CC condensation of 2 farnesyl pyrophosphate moieties to form squalene,
CC which is the precursor of all steroids. Secondly, squalene is converted
CC into lanosterol by the consecutive action of the squalene epoxidase
CC erg1 and the lanosterol synthase erg7. The lanosterol 14-alpha-
CC demethylase erg11/cyp1 catalyzes C14-demethylation of lanosterol to
CC produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol. In the next
CC steps, a complex process involving various demethylation, reduction and
CC desaturation reactions catalyzed by the C-14 reductase erg24 and the C-
CC 4 demethylation complex erg25-erg26-erg27 leads to the production of
CC zymosterol. Erg28 likely functions in the C-4 demethylation complex
CC reaction by tethering erg26 and Erg27 to the endoplasmic reticulum or
CC to facilitate interaction between these proteins. Then, the sterol 24-
CC C-methyltransferase erg6 catalyzes the methyl transfer from S-adenosyl-
CC methionine to the C-24 of zymosterol to form fecosterol. The C-8 sterol
CC isomerase erg2 catalyzes the reaction which results in unsaturation at
CC C-7 in the B ring of sterols and thus converts fecosterol to episterol.
CC The sterol-C5-desaturases erg31 and erg32 then catalyze the
CC introduction of a C-5 double bond in the B ring to produce 5-
CC dehydroepisterol. The C-22 sterol desaturase erg5 further converts 5-
CC dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming
CC the C-22(23) double bond in the sterol side chain. Finally, ergosta-
CC 5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28) sterol
CC reductase erg4 to produce ergosterol (PubMed:18310029) (Probable). In
CC the genus Schizosaccharomyces, a second route exists between lanosterol
CC and fecosterol, via the methylation of lanosterol to eburicol by erg6,
CC followed by C14-demethylation by erg11/cyp1 and C4-demethylation by the
CC demethylation complex erg25-erg26-erg27 (PubMed:8586261) (Probable).
CC {ECO:0000250|UniProtKB:P53199, ECO:0000305|PubMed:18310029,
CC ECO:0000305|PubMed:8586261}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3-
CC dehydro-4-methylzymosterol + CO2 + NADPH; Xref=Rhea:RHEA:33447,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:50593, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:64925; EC=1.1.1.170;
CC Evidence={ECO:0000250|UniProtKB:P53199};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33448;
CC Evidence={ECO:0000250|UniProtKB:P53199};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 4/6. {ECO:0000250|UniProtKB:P53199}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC {ECO:0000250|UniProtKB:P53199}.
CC -!- SUBUNIT: Heterotetramer of erg25, erg26, erg27 and erg28 (By
CC similarity). Erg28 acts as a scaffold to tether erg27 and other 4,4-
CC demethylation-related enzymes, forming a demethylation enzyme complex,
CC in the endoplasmic reticulum (By similarity).
CC {ECO:0000250|UniProtKB:P53199}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16823372}; Peripheral membrane protein
CC {ECO:0000269|PubMed:16823372}.
CC -!- MISCELLANEOUS: In Aspergillus, the biosynthesis pathway of the sterol
CC precursors leading to the prevalent sterol ergosterol differs from
CC yeast. The ringsystem of lanosterol in S.cerevisiae is firstly
CC demethylised in three enzymatic steps leading to the intermediate
CC zymosterol and secondly a methyl group is added to zymosterol by the
CC sterol 24-C-methyltransferase to form fecosterol. In Aspergillus,
CC lanosterol is firstly transmethylated by the sterol 24-C-
CC methyltransferase leading to the intermediate eburicol and secondly
CC demethylated in three steps to form fecosterol. In the genus
CC Schizosaccharomyces, 2 routes exist from lanosterol to erposterol: the
CC classical one via zymosterol and the second one via the formation of
CC eburicol followed by demethylation. {ECO:0000269|PubMed:8586261}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; CU329671; CAA17691.1; -; Genomic_DNA.
DR PIR; T40392; T40392.
DR RefSeq; NP_596741.1; NM_001022667.2.
DR AlphaFoldDB; O43050; -.
DR SMR; O43050; -.
DR BioGRID; 277160; 4.
DR STRING; 4896.SPBC3F6.02c.1; -.
DR MaxQB; O43050; -.
DR PaxDb; O43050; -.
DR EnsemblFungi; SPBC3F6.02c.1; SPBC3F6.02c.1:pep; SPBC3F6.02c.
DR GeneID; 2540634; -.
DR KEGG; spo:SPBC3F6.02c; -.
DR PomBase; SPBC3F6.02c; erg26.
DR VEuPathDB; FungiDB:SPBC3F6.02c; -.
DR eggNOG; KOG1430; Eukaryota.
DR HOGENOM; CLU_007383_6_8_1; -.
DR InParanoid; O43050; -.
DR OMA; NERITFR; -.
DR PhylomeDB; O43050; -.
DR Reactome; R-SPO-191273; Cholesterol biosynthesis.
DR Reactome; R-SPO-193048; Androgen biosynthesis.
DR Reactome; R-SPO-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-SPO-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-SPO-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-SPO-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-SPO-194002; Glucocorticoid biosynthesis.
DR UniPathway; UPA00768; -.
DR UniPathway; UPA00770; UER00757.
DR PRO; PR:O43050; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:PomBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; HDA:PomBase.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IEA:InterPro.
DR GO; GO:0103066; F:4alpha-carboxy-4beta-methyl-5alpha-cholesta-8-en-3beta-ol:NAD(P)+ 3-oxidoreductase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0103067; F:4alpha-carboxy-5alpha-cholesta-8-en-3beta-ol:NAD(P)+ 3-dehydrogenase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0000252; F:C-3 sterol dehydrogenase (C-4 sterol decarboxylase) activity; ISO:PomBase.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0047012; F:sterol-4-alpha-carboxylate 3-dehydrogenase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0006696; P:ergosterol biosynthetic process; ISO:PomBase.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane; NAD;
KW Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism.
FT CHAIN 1..340
FT /note="Sterol-4-alpha-carboxylate 3-dehydrogenase erg26,
FT decarboxylating"
FT /id="PRO_0000357024"
FT ACT_SITE 144
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 148
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
SQ SEQUENCE 340 AA; 38318 MW; 493ADB21D10E7B50 CRC64;
MPMNSVLVIG SGFLGGHIIR QLCERENLRI AAFDLFENEK LLHELHGQFT MYTGDLTKQG
DIERVFEEFH PRVVIHTASP VHNLARDIYF EVNVDGTANI IKACQKFNVD ALVYTSSAGV
VFNGADLINV DESQPIPEVH MDAYNESKAL AEKQVLEASS ESLKTAALRV AGLFGPGDRQ
LVPGMLSVLK NGQTKFQLGD NLNLFDFTYI ENAAYAHLLA MDNLLSSNPT ANGQVFFITN
GQVIYFWDFA RAIWAHAGHV PPYIIKFPRP VGMLLATAAE WVCYFLKKEP GFTRFRVQFS
CANRYFNIQK AEDVLKYHPI VDLEEGIRRT LAWMDTEKKH
