HMDH1_DICDI
ID HMDH1_DICDI Reviewed; 552 AA.
AC P34135; Q55CJ2;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase 1;
DE Short=HMG-CoA reductase 1;
DE EC=1.1.1.34;
GN Name=hmgA; ORFNames=DDB_G0269142;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=AX3;
RA De Lozanne A.;
RT "The dictyostelium HMGCoA reductase genes.";
RL Submitted (JUN-1993) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: This transmembrane glycoprotein is involved in the control of
CC cholesterol biosynthesis. It is the rate-limiting enzyme of the 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.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; L19349; AAA33214.1; -; mRNA.
DR EMBL; AAFI02000005; EAL71921.1; -; Genomic_DNA.
DR RefSeq; XP_646489.1; XM_641397.1.
DR AlphaFoldDB; P34135; -.
DR SMR; P34135; -.
DR STRING; 44689.DDB0191125; -.
DR PaxDb; P34135; -.
DR PRIDE; P34135; -.
DR EnsemblProtists; EAL71921; EAL71921; DDB_G0269142.
DR GeneID; 8617451; -.
DR KEGG; ddi:DDB_G0269142; -.
DR dictyBase; DDB_G0269142; hmgA.
DR eggNOG; KOG2480; Eukaryota.
DR HOGENOM; CLU_001734_2_2_1; -.
DR InParanoid; P34135; -.
DR OMA; AHFANGI; -.
DR PhylomeDB; P34135; -.
DR Reactome; R-DDI-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00058; UER00103.
DR PRO; PR:P34135; -.
DR Proteomes; UP000002195; Chromosome 1.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
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: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; 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; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism.
FT CHAIN 1..552
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase 1"
FT /id="PRO_0000114427"
FT REGION 79..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 237
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 369
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 445
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 543
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 552 AA; 60387 MW; 3535CF268CDCE693 CRC64;
MLFAPPNLET KELFWIIYIL ILIPKVFAKV MSVRELFPFF KWGFNIRRSN FLVPILSNNV
IVTGEEAVQY EKPLPYIPQH NQQQQQKQQP SQDYIQQPQN DNNINSGKEQ EQQQQQQQQQ
QQTPDITNQP TKTNKKIPIK ELSNEEILIK LEKGEVLAYR LENELGDCSR AVEIRRMLLE
KQLSKKIEPI PHEGFDFAKV QGQCCENVIG YVPIPVGTAG PIQLNGQLVT IPMATTEGCL
VASTHRGCKA ITESGGAKCT ITSRGMTRAP VVRFSDIVKA SEFVSWINDT DNYQALKAVF
DSTSRFARLS AIKCTIAGRS VYIRFKCDTG DAMGMNMVSK GVEAVLEHLK IIFDDMTLLS
ISGNMCTDKK PSSINWTEGR GRSVVCEAMI TGDVVQRVLK TNVQALVDLN IAKNLIGSAM
AGSIGGFNAH ASNIVTAIFL ATGQDCAQNV ESSNCITQME ACNDGQDLYI TVTMPSIEVG
TVGGGTSLPA QSACLDIIGV KGSSSSKPGA NADQLAKTIA SAVMAGELSL MSALSAGHLM
KSHLQYNRAK TN
