HMDH_CANAL
ID HMDH_CANAL Reviewed; 1073 AA.
AC A0A1D8PD39;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 {ECO:0000303|PubMed:14653518};
DE Short=HMG-CoA reductase 1 {ECO:0000303|PubMed:14653518};
DE EC=1.1.1.34 {ECO:0000305|PubMed:14653518};
GN Name=HMG1 {ECO:0000303|PubMed:14653518}; OrderedLocusNames=orf19.1031;
GN ORFNames=CAALFM_C103780CA;
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, INDUCTION, AND PATHWAY.
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: HMG-CoA reductase; part of the first module of ergosterol
CC biosynthesis pathway that includes the early steps of the pathway,
CC conserved across all eukaryotes, and which results in the formation of
CC mevalonate from acetyl-coenzyme A (acetyl-CoA) (By similarity). HMG1
CC catalyzes the reduction of hydroxymethylglutaryl-CoA (HMG-CoA) to
CC mevalonate (By similarity). The first module starts with the action of
CC the cytosolic acetyl-CoA acetyltransferase ERG10 that catalyzes the
CC formation of acetoacetyl-CoA. The hydroxymethylglutaryl-CoA synthase
CC ERG13 then condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA.
CC The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase HMG1
CC finally reduces HMG-CoA to produce mevalonate (Probable).
CC {ECO:0000250|UniProtKB:P12683, ECO:0000305|PubMed:14653518}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + CoA + 2 NADP(+) = (3S)-hydroxy-3-
CC methylglutaryl-CoA + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:15989,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.34;
CC Evidence={ECO:0000305|PubMed:14653518};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15990;
CC Evidence={ECO:0000305|PubMed:14653518};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000305|PubMed:14653518}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P12683}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Expression is not affected by lovastatin or fluconazole.
CC {ECO:0000269|PubMed:14653518}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; CP017623; AOW26055.1; -; Genomic_DNA.
DR RefSeq; XP_713636.2; XM_708543.2.
DR AlphaFoldDB; A0A1D8PD39; -.
DR SMR; A0A1D8PD39; -.
DR STRING; 237561.A0A1D8PD39; -.
DR GeneID; 3644687; -.
DR KEGG; cal:CAALFM_C103780CA; -.
DR CGD; CAL0000177752; HMG1.
DR VEuPathDB; FungiDB:C1_03780C_A; -.
DR eggNOG; KOG2480; Eukaryota.
DR OrthoDB; 907394at2759; -.
DR UniPathway; UPA00058; UER00103.
DR Proteomes; UP000000559; Chromosome 1.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005778; C:peroxisomal membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:CGD.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IBA:GO_Central.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR CDD; cd00643; HMG-CoA_reductase_classI; 1.
DR Gene3D; 1.10.3270.10; -; 1.
DR Gene3D; 3.30.70.420; -; 1.
DR Gene3D; 3.90.770.10; -; 1.
DR InterPro; IPR025583; HMG-CoA_N_dom.
DR InterPro; IPR002202; HMG_CoA_Rdtase.
DR InterPro; IPR023074; HMG_CoA_Rdtase_cat_sf.
DR InterPro; IPR023076; HMG_CoA_Rdtase_CS.
DR InterPro; IPR004554; HMG_CoA_Rdtase_eu_arc.
DR InterPro; IPR023282; HMG_CoA_Rdtase_N.
DR InterPro; IPR009023; HMG_CoA_Rdtase_NAD(P)-bd_sf.
DR InterPro; IPR009029; HMG_CoA_Rdtase_sub-bd_dom_sf.
DR InterPro; IPR000731; SSD.
DR PANTHER; PTHR10572; PTHR10572; 1.
DR Pfam; PF00368; HMG-CoA_red; 1.
DR Pfam; PF13323; HPIH; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR PRINTS; PR00071; HMGCOARDTASE.
DR SUPFAM; SSF55035; SSF55035; 1.
DR SUPFAM; SSF56542; SSF56542; 1.
DR TIGRFAMs; TIGR00533; HMG_CoA_R_NADP; 1.
DR PROSITE; PS00066; HMG_COA_REDUCTASE_1; 1.
DR PROSITE; PS00318; HMG_COA_REDUCTASE_2; 1.
DR PROSITE; PS01192; HMG_COA_REDUCTASE_3; 1.
DR PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
DR PROSITE; PS50156; SSD; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1073
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase 1"
FT /id="PRO_0000454165"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 326..346
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 399..419
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 459..479
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 498..518
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 997..1017
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 182..346
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 542..589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1025..1056
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..575
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 714
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 848
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 924
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1022
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT BINDING 720..726
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 781..783
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 808..816
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 877..879
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1021..1022
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1026..1027
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
SQ SEQUENCE 1073 AA; 116476 MW; 78E15C0BDC2BE4A6 CRC64;
MLSFLTEVTG AIAQTSARRP IQFMVVPALL ASIAYLSIID DYIPEHIKSS SGSSGISYYH
PYTSSHYKSQ PDLDKWTAID KEHINDDIYT QANQISVIPL RFRRFQDVVP NVPNAIHISD
NEQILIVPTD QIENSLDQLQ EITNNGITWK ARNNDKLAKY YDYIRYGLNK VQDAIQHAEN
FDILLIFVAY LGMWYALIKV FVDMRKIGSK FWLAFSTLTS STFAFLLALL VSNKFLHTKV
SLLSLSEGIP FLVSVIGFKH KVSIATIVAN SSTASPEDVP HVVGKAVSSH CLSMLRDHLV
VIGGLLSCAI YAHHLTGLRN FCILSSLILS FDLILVYTFF SAILGLKVEI NRARRTEDLQ
NALEEEGISS LVAARVAEQS ATIEHPNEHN FFKSNNSSIA YFKVIMSLGF FAFHAFWLGS
SWLYSTTDGG ESFSRFSFLS NIPTLSQDIS QQIPIGRKGT VVTILPTIFF MPSGFMVQLE
DFIYLVLSKF SSAIRDSIIS KFLVFGFALS IVTNVYFLNA ARYQVSATHK LIEKEISRPQ
DSSVTATTTT TATGTTSSGA ATSKTIGNNK GLKSVQEIPD NEDESSDEEL EIKAPVKVLP
LEECVKVLKE GKVKTLSNDE VSSLVVGGKL PLYALEKQLA DNKRAVIVRR KAIAKLANAP
VLDTNRLPYA HYDYDRVFGA CCENVIGYMP LPVGVAGPLI IDEKPYHIPM ATTEGCLVAS
TMRGCKAINA GGGVETVLTR DGMTRGPCVR FPTLKRAGAA KLWIDSEQGQ ATIKKAFNST
SRFARLQHIQ TALAGTSLFI RFRTTTGDAM GMNMISKGVE YSLKYMVEEC GWDDMEIVSV
SGNYCTDKKP AAINWIEGRG KSIVAAARIP ADVVTKVLKS DVDALVELNI SKNLVGSAMA
GSVGGFNAHA ANLVTAVYLA CGQDPAQNVE SSNCITLMEK DKETGDLNVS VSMPSIEVGT
IGGGTILEPQ GAMLDLLGVR GPHPTNPGAN AQQLAKIVAS AVLAAELSLC SALAAGHLVQ
SHMQHNRSKA PAAGATTTTT PAITDSKASN GSIASNGKDL KRLEEGSVTC IKS
