HMDH_PHYB8
ID HMDH_PHYB8 Reviewed; 1176 AA.
AC Q12649;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 29-AUG-2001, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase {ECO:0000303|Ref.2};
DE Short=HMG-CoA reductase {ECO:0000303|Ref.2};
DE EC=1.1.1.34 {ECO:0000305|Ref.2};
GN Name=hmgA {ECO:0000303|Ref.2};
OS Phycomyces blakesleeanus (strain ATCC 8743b / DSM 1359 / FGSC 10004 / NBRC
OS 33097 / NRRL 1555).
OC Eukaryota; Fungi; Fungi incertae sedis; Mucoromycota; Mucoromycotina;
OC Mucoromycetes; Mucorales; Phycomycetaceae; Phycomyces.
OX NCBI_TaxID=763407;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 8743b / DSM 1359 / FGSC 10004 / NBRC 33097 / NRRL 1555;
RA Ruiz-Albert J., Cerda-Olmedo E., Corrochano L.M.;
RT "Genes for the metabolism of 3-hydroxy-3-methylglutaryl coenzyme A in the
RT fungus Phycomyces.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 836-940.
RC STRAIN=ATCC 8743b / DSM 1359 / FGSC 10004 / NBRC 33097 / NRRL 1555;
RX DOI=10.1016/0147-5975(92)90024-L;
RA Corrochano L.M., Avalos J.;
RT "Cloning a segment of the gene encoding 3-hydroxy-3-methyglutaryl coenzyme
RT A reductase in Phycomyces blakesleeanus and Gibberella fujikuroi by the
RT polymerase chain reaction.";
RL Exp. Mycol. 16:167-171(1992).
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) (Probable). In this
CC module, the cytosolic acetyl-CoA acetyltransferase catalyzes the
CC formation of acetoacetyl-CoA (By similarity). The
CC hydroxymethylglutaryl-CoA synthase then condenses acetyl-CoA with
CC acetoacetyl-CoA to form HMG-CoA (By similarity). The rate-limiting step
CC of the early module is the reduction to mevalonate by the 3-hydroxy-3-
CC methylglutaryl-coenzyme A (HMG-CoA) reductase hmgA (Probable).
CC {ECO:0000250|UniProtKB:Q4WHZ1, ECO:0000305|Ref.2}.
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:0000255|PROSITE-ProRule:PRU10003, ECO:0000305|Ref.2};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000305|Ref.2}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X58371; CAB97179.1; -; Genomic_DNA.
DR PIR; S17345; S17345.
DR AlphaFoldDB; Q12649; -.
DR SMR; Q12649; -.
DR UniPathway; UPA00058; UER00103.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
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; 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; IPR004816; HMG_CoA_Rdtase_metazoan.
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; PF12349; Sterol-sensing; 1.
DR PRINTS; PR00071; HMGCOARDTASE.
DR SUPFAM; SSF55035; SSF55035; 1.
DR SUPFAM; SSF56542; SSF56542; 1.
DR TIGRFAMs; TIGR00920; 2A060605; 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 3: Inferred from homology;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; NADP; Oxidoreductase; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..1176
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114453"
FT TOPO_DOM 1..34
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 35..55
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 56..299
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 300..320
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 321..330
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 331..351
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 352..355
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 356..376
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 377..422
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 444
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 445..465
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 466..524
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 525..545
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 546..622
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 623..643
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 644..1176
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT DOMAIN 301..465
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 699..724
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1153..1176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 701..718
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 841
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 972
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1048
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1146
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT BINDING 847..853
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 907..909
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 934..942
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1001..1003
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1145..1146
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1150..1151
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 553
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 596
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1176 AA; 127819 MW; 6BA5C23E828DF35F CRC64;
MSLPNHSGSS AFKSFSYIVG TGIKRAAKLS TRNPIEMIVV VLILSSFSYF YLFNLARTSD
IFSGTVTRLY PTSVYAPTKD HSFSVVDRTA DSTIANNAVK VHLHQIVVSD PKHGVLSRQT
LASVLRFQQM AENEIYVPDS TAVNRFAFNK DLCYKTTLPS SYSSHSSDSN SNSNLNSKTS
PCFAHSPADI WQDEATLLAD KNIRSTIEAN LDTAKNVFGD LQLNATYASS VTLSYAFNTT
GDYREHLADM WKHKVATLPP ADLVSLSNIG QQENVFAWLF IVTRNVIFRV KELIDLADNI
DIIVILVGYI MMIATFISLY VNMRAMGSRY TLATAVVFNG FFSFMLALLT VRALGVDVYP
VVLAEAIPFL AVTIGFERPF KLTKRVFQFS KETPLTKQEI RTTIMRAVDT VALPIARDCF
MEIIVLVLGA KSGISGLEEF CLLSAILLAY DFIIMFTWYT AVLALKLELL RIREINGISA
DDIKKGTKKS TGYIRRTVIK AFSDDHAAGA NTANQKADGP IIGRVKLLMI VGFVVMHIFK
FCSAFQSVGP QVNITEPSIA VVLDQLLEQH KASSQASLPL FVQVFPAMPF HVATVNKSFV
PDAITRPLEA LFDTYAVYIQ HPVISKWLTI ALFVSLFLNT YLFNVAKQPK QIVEQVNQDK
KITNAIESTN NTHIEVTEKQ KPTIQSPGPV VSSAVVMSPN HKRSHNHHHS HSHSHNHHSN
HHQSDIVRPI DECVALVRTP EMLNDEEVIS LVENGKMASY ALEKVLGDLQ RAVGIRRALI
SRASITKTLE ASALPLENYH YDKVMGACCE NVIGYMPIPV GVAGPMNIDG DLIHIPMATT
EGCLVASTAR GCKAINAGGG ASTIVIADGM TRGPCVEFPT ILRAAACKLW IENEGNDIVT
NAFNSTSRFA RLRKLKIALA GKLVFIRFST TTGDAMGMNM ISKGCEKALS IITEHFPDMQ
IISLSGNYCT DKKPAAINWI EGRGKSVVTE AVIPGAIVEK VLKTTVAALV ELNISKNLIG
SAMAGSVGGF NAHAANILTA IYLATGQDPA QNVESSNCIT LMKAVNDTKD LHISCTMPSI
EVGTIGGGTI LPPQQSMLDM LGVRGPHPTE PGKNAQRLAR IICAAVMAGE LSLCAALAAG
HLVKAHMAHN RGTQAPTITS GPAPSTGTEP GTCIKS
