ERG8_ASPFU
ID ERG8_ASPFU Reviewed; 484 AA.
AC Q4WV38;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Phosphomevalonate kinase erg8 {ECO:0000303|PubMed:16110826};
DE EC=2.7.4.2 {ECO:0000305|PubMed:22106303};
DE AltName: Full=Ergosterol biosynthesis protein 8 {ECO:0000303|PubMed:16110826};
GN Name=erg8 {ECO:0000303|PubMed:16110826}; ORFNames=AFUA_5G10680;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP IDENTIFICATION, AND FUNCTION.
RX PubMed=16110826; DOI=10.1080/13693780400029114;
RA Ferreira M.E., Colombo A.L., Paulsen I., Ren Q., Wortman J., Huang J.,
RA Goldman M.H., Goldman G.H.;
RT "The ergosterol biosynthesis pathway, transporter genes, and azole
RT resistance in Aspergillus fumigatus.";
RL Med. Mycol. 43:S313-S319(2005).
RN [3]
RP FUNCTION.
RX PubMed=22106303; DOI=10.1073/pnas.1106399108;
RA Yasmin S., Alcazar-Fuoli L., Gruendlinger M., Puempel T., Cairns T.,
RA Blatzer M., Lopez J.F., Grimalt J.O., Bignell E., Haas H.;
RT "Mevalonate governs interdependency of ergosterol and siderophore
RT biosyntheses in the fungal pathogen Aspergillus fumigatus.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E497-E504(2012).
CC -!- FUNCTION: Phosphomevalonate kinase; part of the second module of
CC ergosterol biosynthesis pathway that includes the middle steps of the
CC pathway (By similarity). 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 (AFUA_4G07780) first converts mevalonate into
CC 5-phosphomevalonate. 5-phosphomevalonate is then further converted to
CC 5-diphosphomevalonate by the phosphomevalonate kinase erg8
CC (AFUA_5G10680). The diphosphomevalonate decarboxylase mvd1
CC (AFUA_4G07130) then produces isopentenyl diphosphate. The isopentenyl-
CC diphosphate delta-isomerase idi1 (AFUA_6G11160) then catalyzes the 1,3-
CC allylic rearrangement of the homoallylic substrate isopentenyl (IPP) to
CC its highly electrophilic allylic isomer, dimethylallyl diphosphate
CC (DMAPP). Finally the farnesyl diphosphate synthase erg20 (AFUA_5G02450)
CC catalyzes the sequential condensation of isopentenyl pyrophosphate with
CC dimethylallyl pyrophosphate, and then with the resultant
CC geranylpyrophosphate to the ultimate product farnesyl pyrophosphate
CC (PubMed:16110826, PubMed:22106303) (Probable).
CC {ECO:0000250|UniProtKB:P24521, ECO:0000305|PubMed:16110826,
CC ECO:0000305|PubMed:22106303}.
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:0000305|PubMed:16110826};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16342;
CC Evidence={ECO:0000305|PubMed:16110826};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 2/3. {ECO:0000305|PubMed:16110826}.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC subfamily. {ECO:0000305}.
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DR EMBL; AAHF01000003; EAL91538.1; -; Genomic_DNA.
DR RefSeq; XP_753576.1; XM_748483.1.
DR STRING; 746128.CADAFUBP00005702; -.
DR EnsemblFungi; EAL91538; EAL91538; AFUA_5G10680.
DR GeneID; 3510941; -.
DR KEGG; afm:AFUA_5G10680; -.
DR VEuPathDB; FungiDB:Afu5g10680; -.
DR eggNOG; KOG4519; Eukaryota.
DR HOGENOM; CLU_022059_1_0_1; -.
DR InParanoid; Q4WV38; -.
DR OMA; LVIHRTM; -.
DR OrthoDB; 1165296at2759; -.
DR UniPathway; UPA00057; UER00099.
DR Proteomes; UP000002530; Chromosome 5.
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:0031388; P:organic acid phosphorylation; IEA:EnsemblFungi.
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.
DR SUPFAM; SSF55060; SSF55060; 1.
PE 3: Inferred from homology;
KW ATP-binding; Kinase; Lipid biosynthesis; Lipid metabolism;
KW Nucleotide-binding; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..484
FT /note="Phosphomevalonate kinase erg8"
FT /id="PRO_0000454153"
FT REGION 54..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 184..194
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
SQ SEQUENCE 484 AA; 53232 MW; DF9878A8DBBF36A7 CRC64;
MLPLPPAVTA LSAPGKVLLT GGYLVLDRSY TGTVFALDAR IHVIVQQLRR NHRREAASGS
AHGRSDTPQA EGNVHGDKED EGTIVVHSPQ FVDAVWEYSI QRCEDGGGVL VKQRNDGPRN
LFVETSLNFA LTYISYVADS KDFGSLSITI LADNDYYSET AFSKASGLRS SSRFVDFGVR
LQEAHKTGLG SSAALVTALV SSLVIHRTMQ PDDLGPGRDK LHNLAQAAHC AAQGKVGSGF
DVAAAIYGSC LYRRFSPSIL ESVGDAGSPG FEERLFRIVE DADPQHPWDT ECLDFGMKLP
RGMQMVLCDV ECGSQTPSMV RKVLEWRKQN QKEADMLWGA LQSNNERLRL ELRRLAQSPD
EHTLSDFENV RTYIQRSRNH IRSMTQKSDV PIEPRVQTEL LDALSELEGV IGGVVPGAGG
YDAIVLLIQD NPDVITRLKA FFETWESKAE DDFGGKIGKV RLLGVRHGSE GVKNEMLEQY
AGWV
