ERG8_CANAL
ID ERG8_CANAL Reviewed; 432 AA.
AC A0A1D8PLH0;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Phosphomevalonate kinase {ECO:0000303|PubMed:11243736};
DE EC=2.7.4.2 {ECO:0000250|UniProtKB:P24521};
GN Name=ERG8 {ECO:0000303|PubMed:11243736}; OrderedLocusNames=orf19.4606;
GN ORFNames=CAALFM_C401870CA;
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 IDENTIFICATION, AND FUNCTION.
RX PubMed=11243736; DOI=10.1006/mgme.2000.3133;
RA Houten S.M., Waterham H.R.;
RT "Nonorthologous gene displacement of phosphomevalonate kinase.";
RL Mol. Genet. Metab. 72:273-276(2001).
RN [5]
RP INDUCTION.
RX PubMed=11737641; DOI=10.1046/j.1365-2958.2001.02713.x;
RA Murad A.M., d'Enfert C., Gaillardin C., Tournu H., Tekaia F., Talibi D.,
RA Marechal D., Marchais V., Cottin J., Brown A.J.;
RT "Transcript profiling in Candida albicans reveals new cellular functions
RT for the transcriptional repressors CaTup1, CaMig1 and CaNrg1.";
RL Mol. Microbiol. 42:981-993(2001).
RN [6]
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).
CC -!- FUNCTION: Phosphomevalonate kinase; part of the second module of
CC ergosterol biosynthesis pathway that includes the middle steps of the
CC pathway (PubMed:11243736). ERG8 converts 5-phosphomevalonate to 5-
CC diphosphomevalonate (By similarity). The second module is carried out
CC in the vacuole and involves the formation of farnesyl diphosphate,
CC which is also an important intermediate in the biosynthesis of
CC ubiquinone, dolichol, heme and prenylated proteins. Activity by the
CC mevalonate kinase ERG12 first converts mevalonate into 5-
CC phosphomevalonate. 5-phosphomevalonate is then further converted to 5-
CC diphosphomevalonate by the phosphomevalonate kinase ERG8. The
CC diphosphomevalonate decarboxylase MVD then produces isopentenyl
CC diphosphate. The isopentenyl-diphosphate delta-isomerase IDI1 then
CC catalyzes the 1,3-allylic rearrangement of the homoallylic substrate
CC isopentenyl (IPP) to its highly electrophilic allylic isomer,
CC dimethylallyl diphosphate (DMAPP). Finally the farnesyl diphosphate
CC synthase ERG20 catalyzes the sequential condensation of isopentenyl
CC pyrophosphate with dimethylallyl pyrophosphate, and then with the
CC resultant geranylpyrophosphate to the ultimate product farnesyl
CC pyrophosphate (Probable). {ECO:0000250|UniProtKB:P24521,
CC ECO:0000269|PubMed:11243736, ECO:0000305|PubMed:14653518}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate +
CC ADP; Xref=Rhea:RHEA:16341, ChEBI:CHEBI:30616, ChEBI:CHEBI:57557,
CC ChEBI:CHEBI:58146, ChEBI:CHEBI:456216; EC=2.7.4.2;
CC Evidence={ECO:0000250|UniProtKB:P24521};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16342;
CC Evidence={ECO:0000250|UniProtKB:P24521};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 2/3. {ECO:0000305|PubMed:14653518}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- INDUCTION: Expression is regulated by the transcription factor NRG1.
CC {ECO:0000269|PubMed:11737641}.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC subfamily. {ECO:0000305}.
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DR EMBL; CP017626; AOW28958.1; -; Genomic_DNA.
DR RefSeq; XP_722678.1; XM_717585.1.
DR AlphaFoldDB; A0A1D8PLH0; -.
DR SMR; A0A1D8PLH0; -.
DR STRING; 237561.A0A1D8PLH0; -.
DR GeneID; 3635640; -.
DR KEGG; cal:CAALFM_C401870CA; -.
DR CGD; CAL0000200676; ERG8.
DR VEuPathDB; FungiDB:C4_01870C_A; -.
DR eggNOG; KOG4519; Eukaryota.
DR OrthoDB; 1165296at2759; -.
DR UniPathway; UPA00057; UER00099.
DR Proteomes; UP000000559; Chromosome 4.
DR GO; GO:0005777; C:peroxisome; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004631; F:phosphomevalonate kinase activity; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; 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; IPR016005; Erg8.
DR InterPro; IPR013750; GHMP_kinase_C_dom.
DR InterPro; IPR036554; GHMP_kinase_C_sf.
DR InterPro; IPR006204; GHMP_kinase_N_dom.
DR InterPro; IPR035102; Phosphomevalonate_kinase.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR31814; PTHR31814; 1.
DR Pfam; PF08544; GHMP_kinases_C; 1.
DR Pfam; PF00288; GHMP_kinases_N; 1.
DR PIRSF; PIRSF017288; PMK_GHMP_euk; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Kinase; Lipid biosynthesis; Lipid metabolism;
KW Nucleotide-binding; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Transferase.
FT CHAIN 1..432
FT /note="Phosphomevalonate kinase"
FT /id="PRO_0000454166"
FT BINDING 10
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 142..148
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
SQ SEQUENCE 432 AA; 48280 MW; 384D7FC05886B17E CRC64;
MSKAFSAPGK AFLAGGYLVL EPIYDAYVTA LSSRMHAVIT PKGTSLKESR IKISSPQFAN
GEWEYHISSN TEKPKEVQSR INPFLEATIF IVLAYIQPTE AFDLEIIIYS DPGYHSQEDT
ETKTSSNGEK TFLYHSRAIT EVEKTGLGSS AGLVSVVATS LLSHFIPNVI STNKDILHNV
AQIAHCYAQK KIGSGFDVAT AIYGSIVYRR FQPALINDVF QVLESDPEKF PTELKKLIAS
NWEFKHERCT LPHGIKLLMG DVKGGSETPK LVSRVLQWKK EKPEESSVVY DQLNSANLQF
MKELREMREK YDSDPETYIK ELDHSIEPLT VAIKNIRKGL QALTQKSEVP IEPDVQTQLL
DRCQEIPGCV GGVVPGAGGY DAIAVLVLEN QVGNFKQKTL ENPDYFHNVY WVDLEEQTEG
VLEEKPEDYI GL
