HMDH_CYBJA
ID HMDH_CYBJA Reviewed; 934 AA.
AC O74164;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase {ECO:0000303|PubMed:9647847};
DE Short=HMG-CoA reductase {ECO:0000303|PubMed:9647847};
DE EC=1.1.1.34 {ECO:0000269|PubMed:9647847};
GN Name=HMG {ECO:0000303|PubMed:9647847};
OS Cyberlindnera jadinii (Torula yeast) (Pichia jadinii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Phaffomycetaceae; Cyberlindnera.
OX NCBI_TaxID=4903;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=9647847; DOI=10.1128/aem.64.7.2676-2680.1998;
RA Shimada H., Kondo K., Fraser P.D., Miura Y., Saito T., Misawa N.;
RT "Increased carotenoid production by the food yeast Candida utilis through
RT metabolic engineering of the isoprenoid pathway.";
RL Appl. Environ. Microbiol. 64:2676-2680(1998).
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) (PubMed:9647847). In
CC this 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 (PubMed:9647847).
CC {ECO:0000250|UniProtKB:Q4WHZ1, ECO:0000269|PubMed:9647847}.
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:0000269|PubMed:9647847};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000269|PubMed:9647847}.
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}.
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DR EMBL; AB012603; BAA31937.1; -; mRNA.
DR AlphaFoldDB; O74164; -.
DR SMR; O74164; -.
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: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; 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; 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 1: Evidence at protein level;
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..934
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114454"
FT TOPO_DOM 1..111
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 112..132
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..141
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..168
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 253..256
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 257..277
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 278..334
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 335..355
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 356..421
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 443..934
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT DOMAIN 113..280
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT ACT_SITE 618
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 752
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 828
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 924
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT BINDING 624..630
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 685..687
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 712..720
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 781..783
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 923..924
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 928..929
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 934 AA; 101234 MW; 3C3E43FC5623601C CRC64;
MFYHGASANQ HWIAVDDLSK VPVDVDHYNV VPFQFRRAGE YKEPVLSGIV ELDEVKFVVS
QSDAAEQWQQ LTAEDGTVWR SRAYHGKLGK YSDMAVGAFN KVLNLVRGAE TFDIALVTCA
YIAMFYTLFN LFARMRAVGS KVWLGLSTLV SSFFAFLFAL YITTRVLDLS IPFLSLSEGI
PFFVAVVGFN NKILLAEKVL QNQLNAQSSK NDAPTVLYQA LREQGPLLLR DHLFMITAFL
GCSFYASYLD GLKNFCILAA LILAFDILTT STFLSAILSL KLEINQIHRS TLLREQLEDD
GLTETTVDDV LKSNSLAGTK TFTDAPSTLV TVAKVAGVSV FFGLHFYGFG SAWLSDLSAG
NETNDTFTLY DAVADQIPIG SNGTLVTLFP TRFFLPEKLS TQIEAVVLSF IGLISTAARD
KYISKFILFA FAVSASINVY LLNVARIHTT RLEDAIELKK PKKKASKTAV SVPKAVVVKD
SETTKSSEIL HSSSESESEQ SSRPLEQVIE LYKDGKVKTL VDDEVVSLVT AGKLPLYALE
KQLGDNLRAV AIRRKAISDL ADAPVLRSNK LPYLHYDYDR VFGACCENVI GYMPLPVGVA
GPLIIDGKPY HIPMATTEGC LVASAMRGCK AINLGGGVTT VLTKDGMTRG PCVKFPSLKR
AGQCKLWLDS DEGQEEMKKA FNSTSRFARL QHLQTALAGD LLFIRFRTVT GDAMGMNMIS
KGVEYALKQM TEVFGWDDMM VVSVSGNYCT DKKPAAVNWI NGRGKSVVAE ASIPKDAVVK
VLKSSVKAVV DVNVNKNLIG SAMAGSVGGF NAQAANMVTA VYLALGQDPA QNVESSNCIT
LMTETEDGDL KVSVSMPSIE VGTIGGGTIL DPQGSMLELL GVRGPADVPG ENARQLAKIV
ASIVLSGELS LVSALAAGHL VQSHMQHNRA AAKK
