ID   HMDH_STRPU              Reviewed;         932 AA.
AC   P16393;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 2.
DT   25-MAY-2022, entry version 135.
DE   RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE            Short=HMG-CoA reductase;
DE            EC=1.1.1.34;
GN   Name=HMGCR;
OS   Strongylocentrotus purpuratus (Purple sea urchin).
OC   Eukaryota; Metazoa; Echinodermata; Eleutherozoa; Echinozoa; Echinoidea;
OC   Euechinoidea; Echinacea; Camarodonta; Echinidea; Strongylocentrotidae;
OC   Strongylocentrotus.
OX   NCBI_TaxID=7668;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3192541; DOI=10.1016/s0021-9258(19)81374-1;
RA   Woodward H.D., Allen J.M.C., Lennarz W.J.;
RT   "3-hydroxy-3-methylglutaryl-coenzyme A reductase of the sea urchin embryo.
RT   Deduced structure and regulatory properties.";
RL   J. Biol. Chem. 263:18411-18418(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 689-735.
RX   PubMed=3276692; DOI=10.1016/s0021-9258(18)69236-1;
RA   Woodward H.D., Allen J.M.C., Lennarz W.J.;
RT   "3-hydroxy-3-methylglutaryl coenzyme A reductase in the sea urchin embryo
RT   is developmentally regulated.";
RL   J. Biol. Chem. 263:2513-2517(1988).
CC   -!- FUNCTION: This transmembrane glycoprotein is involved in the control of
CC       cholesterol biosynthesis. It is the rate-limiting enzyme of sterol
CC       biosynthesis.
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};
CC   -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC       biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC       membrane protein.
CC   -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR   EMBL; J04200; AAA30060.1; -; mRNA.
DR   EMBL; J03523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; A31898; A31898.
DR   RefSeq; NP_999724.1; NM_214559.1.
DR   AlphaFoldDB; P16393; -.
DR   SMR; P16393; -.
DR   STRING; 7668.SPU_005963-tr; -.
DR   EnsemblMetazoa; NM_214559; NP_999724; GeneID_373355.
DR   GeneID; 373355; -.
DR   KEGG; spu:373355; -.
DR   CTD; 3156; -.
DR   eggNOG; KOG2480; Eukaryota.
DR   HOGENOM; CLU_346582_0_0_1; -.
DR   InParanoid; P16393; -.
DR   OMA; CHGWSQS; -.
DR   OrthoDB; 907394at2759; -.
DR   PhylomeDB; P16393; -.
DR   UniPathway; UPA00058; UER00103.
DR   Proteomes; UP000007110; Unassembled WGS sequence.
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:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IBA:GO_Central.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
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; 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   2: Evidence at transcript level;
KW   Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum;
KW   Glycoprotein; Lipid biosynthesis; Lipid metabolism; Membrane; NADP;
KW   Oxidoreductase; Phosphoprotein; Reference proteome; Steroid biosynthesis;
KW   Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..932
FT                   /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT                   /id="PRO_0000114425"
FT   TRANSMEM        20..40
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        59..79
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        92..112
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        113..133
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        162..182
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        193..213
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        322..342
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          343..467
FT                   /note="Linker"
FT   REGION          357..442
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          468..932
FT                   /note="Catalytic"
FT   COMPBIAS        371..433
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        575
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        707
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        783
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        882
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT   MOD_RES         888
FT                   /note="Phosphoserine; by AMPK"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        279
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        850
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        886
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   932 AA;  100966 MW;  A645677DE1142A7B CRC64;
     MLSRLFLAQG RFCSSHPWEV IVCTLTLTIC MLSMNYFTGL PRICGWNYEC APQVKESSLS
     SDVLVMCIMR TLAVAYLYLQ FTKLRTTGSK YILGIAGLFT IFSSFLFSSA VIHLFGLELT
     GLNEALPFFL LLIDLTKASA LTKFALSSTT QNEVVDNIAR GMAILGPTIT LDTVVTTLVI
     SIGTMSSIRK MEVFCCFGIL SLIANYFVFM TFFPACLSLV LELSNSNKYG RPVWHLGRFA
     EVLEEEEDRK PNPVVQRVKM IMRTGLVLVH AHSYWLASND TELMSRDMLY DGNLLTDKKI
     DPTMPLWEFY ATRLWPPTLD YILTAILATV LASHYIFFSD LATYPEKRVS IMEGHEVVNP
     GSDHEDASEV ETIGTLSSSP STSDVRVIES MTSRTQACQT DPVTASPRNS RSSSPVSSHS
     VKPARFTIGS SGSGSEDEEE EVIKEEEVEW VLETELKAPR PMPELLEILN VGKGPNALTD
     DEVQLLVGAK HIPAYKLENI LDNPERGVAV RRQIISKLLP ITDALEKLPY ASYDYSFVSG
     ACCENVIGYM PVPVGVAGPL LLDGQEFQVP MATTEGCLVA STNRGCRALR SAGGIHSVLI
     GDGMTRGPLV RLPSAQEAGA IKQWLEVPEN FAAIKERFES TSRFAKLKSI QTALAGRYMF
     LRFKALTGDA MGMNMISKGT EQALHALQTM FPNIEIMSLS GNYCTDKKVA AINWIEGRGK
     SVVCEATVPA HIVQQVLKTS ASALVDLNIH KNLVGSAMAG SIGGFNAHAA NIVTAIYIAT
     GQDAAQNIAS SNCMTLMETR GPKGGDLYLS CTMPSIELGT VGGGTVLPPQ SACLQMMDVK
     GSNIHGSGLN ASQLARIVCA TVMAGELSLM SALAAGHLVK SHMKHNRSAL NIASPLPSID
     EVATHRRSKS VDFSALKESS AAAPGTCTAN AS