ERG12_ASPFU
ID ERG12_ASPFU Reviewed; 538 AA.
AC Q4WP25;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Mevalonate kinase erg12 {ECO:0000303|PubMed:22106303};
DE Short=MK {ECO:0000305};
DE Short=MvK {ECO:0000305};
DE EC=2.7.1.36 {ECO:0000305|PubMed:22106303};
DE AltName: Full=Ergosterol biosynthesis protein 12 {ECO:0000303|PubMed:16110826};
GN Name=erg12 {ECO:0000303|PubMed:16110826}; ORFNames=AFUA_4G07780;
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, AND INDUCTION.
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: 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 (AFUA_4G07780) first converts mevalonate into 5-phosphomevalonate. 5-
CC phosphomevalonate is then further converted to 5-diphosphomevalonate by
CC the phosphomevalonate kinase erg8 (AFUA_5G10680). The
CC diphosphomevalonate decarboxylase mvd1 (AFUA_4G07130) then produces
CC isopentenyl diphosphate. The isopentenyl-diphosphate delta-isomerase
CC idi1 (AFUA_6G11160) then catalyzes the 1,3-allylic rearrangement of the
CC homoallylic substrate isopentenyl (IPP) to its highly electrophilic
CC allylic isomer, dimethylallyl diphosphate (DMAPP). Finally the farnesyl
CC diphosphate synthase erg20 (AFUA_5G02450) catalyzes the sequential
CC condensation of isopentenyl pyrophosphate with dimethylallyl
CC pyrophosphate, and then with the resultant geranylpyrophosphate to the
CC ultimate product farnesyl pyrophosphate (PubMed:16110826,
CC PubMed:22106303) (Probable). {ECO:0000250|UniProtKB:P07277,
CC ECO:0000305|PubMed:16110826, ECO:0000305|PubMed:22106303}.
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:0000305|PubMed:22106303};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17066;
CC Evidence={ECO:0000305|PubMed:22106303};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P17256};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 1/3. {ECO:0000305|PubMed:22106303}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P17256}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:22106303}.
CC -!- INDUCTION: Expression is down-regulated during iron starvation.
CC {ECO:0000269|PubMed:22106303}.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC subfamily. {ECO:0000305}.
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DR EMBL; AAHF01000005; EAL90009.1; -; Genomic_DNA.
DR RefSeq; XP_752047.1; XM_746954.1.
DR STRING; 746128.CADAFUBP00006313; -.
DR EnsemblFungi; EAL90009; EAL90009; AFUA_4G07780.
DR GeneID; 3509635; -.
DR KEGG; afm:AFUA_4G07780; -.
DR VEuPathDB; FungiDB:Afu4g07780; -.
DR eggNOG; KOG1511; Eukaryota.
DR HOGENOM; CLU_017814_1_1_1; -.
DR InParanoid; Q4WP25; -.
DR OMA; NTVCTYG; -.
DR OrthoDB; 1196330at2759; -.
DR UniPathway; UPA00057; UER00098.
DR PHI-base; PHI:2542; -.
DR Proteomes; UP000002530; Chromosome 4.
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:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IEA:EnsemblFungi.
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..538
FT /note="Mevalonate kinase erg12"
FT /id="PRO_0000454152"
FT REGION 1..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..30
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..83
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 298
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q03426"
FT BINDING 99
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 231
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 236..242
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 242
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 287
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
SQ SEQUENCE 538 AA; 58457 MW; 5962A30CB2061B7B CRC64;
MGNPRGRRTN GSIKTSKGTQ RGTVSNLLSD QPLAARPKVS IVSNDDSQDS SDGGAFTTPS
TTESTLKTTI NGTDSTERNM SRKPSSPMAP AFMVSAPGKV IVYGEHAVVH GKAAMAAAIS
LRSYLLVTTL SKSQRTITMN FRDIGLDHTW NIDELPWDVF HHPSKKKFYY DLVTSLDPEL
VAAIQPHADA VSPDKPEDVR KIHRRSASAF LYLFLSLGSS QNPGAIYTLR STIPIGAGLG
SSASVCVCLS AALLLQIRTL AGPHPDQPPD EAEVQIERIN RWAFVGEMCT HGNPSGVDNT
VSAGGKAVVF RREDYSKPPT VTPLLNFPEL PLLLVDTRQS RSTAVEVAKV GKLKDEYPVV
TDSILEAIDQ VTLAAQQKIQ EISTNGISYR TLEDLGTLIR INHGFLVSLG VSHPRLERIR
ELVDYADIGW TKLTGAGGGG CAITLLRPDI KEEAVRELEE KLSAEGFVKY ETTLGGDGIG
VLWPAVLRNG TDEEGGEEID QQKFENAVGT EGIERLVGVG VQEKREGWKF WKRSPRFS
