HMDH_SCHMA
ID HMDH_SCHMA Reviewed; 948 AA.
AC P16237;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE Short=HMG-CoA reductase;
DE EC=1.1.1.34;
OS Schistosoma mansoni (Blood fluke).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Platyhelminthes; Trematoda;
OC Digenea; Strigeidida; Schistosomatoidea; Schistosomatidae; Schistosoma.
OX NCBI_TaxID=6183;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2813388; DOI=10.1073/pnas.86.21.8217;
RA Rajkovic A., Simonsen J.N., Davis R.E., Rottman F.M.;
RT "Molecular cloning and sequence analysis of 3-hydroxy-3-methylglutaryl-
RT coenzyme A reductase from the human parasite Schistosoma mansoni.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8217-8221(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-236.
RC STRAIN=Puerto Rican;
RX PubMed=7665603; DOI=10.1074/jbc.270.37.21813;
RA Davis R.E., Hardwick C., Tavernier P., Hodgson S., Singh H.;
RT "RNA trans-splicing in flatworms. Analysis of trans-spliced mRNAs and genes
RT in the human parasite, Schistosoma mansoni.";
RL J. Biol. Chem. 270:21813-21819(1995).
CC -!- FUNCTION: This transmembrane glycoprotein is involved in the control of
CC cholesterol and nonsterol isoprenoid compounds biosynthesis. It is the
CC rate-limiting enzyme of sterol 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. Peroxisome membrane; Multi-pass membrane protein.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; M27294; AAA29896.1; -; mRNA.
DR EMBL; AH006565; AAC46885.1; -; Genomic_DNA.
DR PIR; A34416; A34416.
DR AlphaFoldDB; P16237; -.
DR SMR; P16237; -.
DR EnsemblMetazoa; Smp_138590.1; Smp_138590.1; Smp_138590.
DR WBParaSite; Smp_138590.1; Smp_138590.1; Smp_138590.
DR eggNOG; KOG2480; Eukaryota.
DR UniPathway; UPA00058; UER00103.
DR Proteomes; UP000008854; Unassembled WGS sequence.
DR ExpressionAtlas; P16237; baseline.
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:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
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; IEA:InterPro.
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 PANTHER; PTHR10572; PTHR10572; 1.
DR Pfam; PF00368; HMG-CoA_red; 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.
PE 2: Evidence at transcript level;
KW Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum;
KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Membrane; NADP;
KW Oxidoreductase; Peroxisome; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..948
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114432"
FT TRANSMEM 9..25
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 55..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..112
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..302
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..363
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 364..466
FT /note="Linker"
FT REGION 467..948
FT /note="Catalytic"
FT ACT_SITE 567
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 699
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 777
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 869
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 430
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 895
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 948 AA; 107045 MW; CD5B9B84776371BF CRC64;
MLKILNTVLL FFDCFSTGTF FVLLIYLFTR LRTHLLHFSS SNCHLDVIIY QSRAVIIFLV
VFVYFIGVLT CKINDKILVH TMLRNKRQLN TLFYTLILFT FALCSLSSVL FVPYTSFAIF
LLSTSVFLLF SDLSVFFIVL EYYLLEIELV NYEHAKRHCL LSHLFSNQLF VDHMLGMFLK
TSLFSISTTS KYAYLESIFK CTLMEQIIYI MIVFVFLPSF MRIFASYAKR MYGEQKKCLV
SNKGVSSSTR KRRHSYSSGH SYVEYRRMSV HNLIGYVVNP NCHYKCWSTT FVIFVSLIIL
HLNNRYSERI SSFKHNSSEN EVFPVLYHIT AYEVTSIFHF IYNIFHVINA NLVVYLFLGL
FLFKRIRLNK PINSQLRNLN IPKIKETLIS DQVKQSPVLP KFSKKLNDIP LQSRKRIYCL
HKDDDYIDRN DSSSVSTFSN TCKNSNERPS NVLDLDMLTE KIKQGLGHEL SDTEILQLLS
HGRLKTRELE SVVRNPFRAV ELRRLDLSTF LNNPHIIERI PYKDYDYRLV YGQCCEEVIG
YMPIPVGKIG PLLLDGRSHY IPLATTEGCL VASTNRGCRA IFLAGGIKSV VYRDQMTRAP
VVWFPSIIDS VKCIAWIDSE EGFQTLKSAF DKTSAHVNLL SVFACPAGRY IHIRFAARTG
DAMGMNMVSK ATDSALHCLK KYFSNMQVIS LSGNMCTDKK PATINTILGR GKSVIAEAHL
SADVLAQVLH TNAQRLARLT HSKNWIGSAM AGCPGMMGCN AHAANIIAGM FAATGQDLAQ
VVDSSSCLTQ LEVDLSDDSL VASVTMPCLE VGTVGGGTRL SGQRACLDLL DLSVDRPTEH
LSRIIAGTVL AAELSLMAAL DTDDLVKAHM HFNRAKQSTN SHSCSHSTTT DNNDNISNIY
DNHNVALSSK IPVTDNSDIR ESVHSLHVKP FPVKSDLSVN PEISHYTM
