ERG12_CANAL
ID ERG12_CANAL Reviewed; 431 AA.
AC A0A1D8PEL1;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Mevalonate kinase {ECO:0000250|UniProtKB:P07277};
DE Short=MK {ECO:0000250|UniProtKB:P07277};
DE Short=MvK {ECO:0000250|UniProtKB:P07277};
DE EC=2.7.1.36 {ECO:0000250|UniProtKB:P07277};
DE AltName: Full=Ergosterol biosynthesis protein 12 {ECO:0000303|PubMed:17531123};
DE AltName: Full=Regulation of autonomous replication protein 1 {ECO:0000250|UniProtKB:P07277};
GN Name=ERG12 {ECO:0000303|PubMed:17531123}; OrderedLocusNames=orf19.4809;
GN ORFNames=CAALFM_C109460WA;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP FUNCTION.
RX PubMed=14653518; DOI=10.1080/1369378031000137233;
RA Song J.L., Lyons C.N., Holleman S., Oliver B.G., White T.C.;
RT "Antifungal activity of fluconazole in combination with lovastatin and
RT their effects on gene expression in the ergosterol and prenylation pathways
RT in Candida albicans.";
RL Med. Mycol. 41:417-425(2003).
RN [5]
RP INDUCTION.
RX PubMed=17531123;
RA Zeng Y.B., Qian Y.S., Ma L., Gu H.N.;
RT "Genome-wide expression profiling of the response to terbinafine in Candida
RT albicans using a cDNA microarray analysis.";
RL Chin. Med. J. 120:807-813(2007).
CC -!- FUNCTION: Mevalonate kinase; part of the second module of ergosterol
CC biosynthesis pathway that includes the middle steps of the pathway (By
CC similarity). ERG12 converts mevalonate into 5-phosphomevalonate (By
CC similarity). The second module is carried out in the vacuole and
CC involves the formation of farnesyl diphosphate, which is also an
CC important intermediate in the biosynthesis of ubiquinone, dolichol,
CC heme and prenylated proteins. Activity by the mevalonate kinase ERG12
CC first converts mevalonate into 5-phosphomevalonate. 5-phosphomevalonate
CC is then further converted to 5-diphosphomevalonate by the
CC phosphomevalonate kinase ERG8. The diphosphomevalonate decarboxylase
CC MVD then produces isopentenyl diphosphate. The isopentenyl-diphosphate
CC delta-isomerase IDI1 then catalyzes the 1,3-allylic rearrangement of
CC the homoallylic substrate isopentenyl (IPP) to its highly electrophilic
CC allylic isomer, dimethylallyl diphosphate (DMAPP). Finally the farnesyl
CC diphosphate synthase ERG20 catalyzes the sequential condensation of
CC isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then
CC with the resultant geranylpyrophosphate to the ultimate product
CC farnesyl pyrophosphate (Probable). {ECO:0000250|UniProtKB:P07277,
CC ECO:0000305|PubMed:14653518}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+);
CC Xref=Rhea:RHEA:17065, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:36464, ChEBI:CHEBI:58146, ChEBI:CHEBI:456216;
CC EC=2.7.1.36; Evidence={ECO:0000250|UniProtKB:P07277};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17066;
CC Evidence={ECO:0000250|UniProtKB:P07277};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 1/3. {ECO:0000305|PubMed:14653518}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P17256}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305}.
CC -!- INDUCTION: Expression is up-regulated in response to terbinafine.
CC {ECO:0000269|PubMed:17531123}.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC subfamily. {ECO:0000305}.
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DR EMBL; CP017623; AOW26579.1; -; Genomic_DNA.
DR RefSeq; XP_723495.2; XM_718402.2.
DR AlphaFoldDB; A0A1D8PEL1; -.
DR SMR; A0A1D8PEL1; -.
DR STRING; 237561.A0A1D8PEL1; -.
DR GeneID; 3634859; -.
DR KEGG; cal:CAALFM_C109460WA; -.
DR CGD; CAL0000186221; ERG12.
DR VEuPathDB; FungiDB:C1_09460W_A; -.
DR eggNOG; KOG1511; Eukaryota.
DR OrthoDB; 1196330at2759; -.
DR UniPathway; UPA00057; UER00098.
DR Proteomes; UP000000559; Chromosome 1.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004496; F:mevalonate kinase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.70.890; -; 1.
DR InterPro; IPR013750; GHMP_kinase_C_dom.
DR InterPro; IPR036554; GHMP_kinase_C_sf.
DR InterPro; IPR006204; GHMP_kinase_N_dom.
DR InterPro; IPR006203; GHMP_knse_ATP-bd_CS.
DR InterPro; IPR006205; Mev_gal_kin.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR43290; PTHR43290; 1.
DR Pfam; PF08544; GHMP_kinases_C; 1.
DR Pfam; PF00288; GHMP_kinases_N; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55060; SSF55060; 1.
DR TIGRFAMs; TIGR00549; mevalon_kin; 1.
DR PROSITE; PS00627; GHMP_KINASES_ATP; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Kinase; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Metal-binding; Nucleotide-binding; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase.
FT CHAIN 1..431
FT /note="Mevalonate kinase"
FT /id="PRO_0000454167"
FT ACT_SITE 209
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q03426"
FT BINDING 13
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 144..150
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 150
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 198
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
SQ SEQUENCE 431 AA; 47035 MW; FB9AAB582FC6EA4B CRC64;
MSQLPFIVGA PGKVIIFGEH AAVYGKPAIA AALSLRCYLL VSPSSDSNTI RLQFPDIKLD
HSWNIKDLPW EEIKPYLTYD SANKPQIPSE LVPEIVDKLS SFLNGFDNKM HYYACFCFLY
LLMNLCDSKV SGMNFIVRST LPIGAGLGSS ASTSVCLSSA LALMGGWINK PSLHENDKLD
TADIPDLEFI DKWSLIGEKC FHGNPSGIDN AVATFGGAVM FQRTSTPEQP SIRTNMRNFP
AIKLLLTNTK VPKSTADLVA GVGRLNAEFN SISTSILTAI EHLSQEAYKV MMNPMFGREE
TNVLRKLVNI NHGLLVALGV SHPALETVKI IGDKHRIGAT KLTGAGGGGC AITLVNDDVE
ESVIHNAIKE FEDSGYESFE TSLGGKGVGI LFHEDLDDAT KFSESQFCNY VDRAAIEDSL
GMANVKEWKF W
