HMDH2_ARATH
ID HMDH2_ARATH Reviewed; 562 AA.
AC P43256;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase 2;
DE Short=AtHMGR2;
DE Short=HMG-CoA reductase 2;
DE EC=1.1.1.34;
GN Name=HMG2; Synonyms=HMGR2; OrderedLocusNames=At2g17370; ORFNames=F5J6.24;
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=cv. Columbia;
RX PubMed=8302869; DOI=10.1073/pnas.91.3.927;
RA Enjuto M., Balcells L., Campos N., Caelles C., Arro M., Boronat A.;
RT "Arabidopsis thaliana contains two differentially expressed 3-hydroxy-3-
RT methylglutaryl-CoA reductase genes, which encode microsomal forms of the
RT enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:927-931(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=10617197; DOI=10.1038/45471;
RA Lin X., Kaul S., Rounsley S.D., Shea T.P., Benito M.-I., Town C.D.,
RA Fujii C.Y., Mason T.M., Bowman C.L., Barnstead M.E., Feldblyum T.V.,
RA Buell C.R., Ketchum K.A., Lee J.J., Ronning C.M., Koo H.L., Moffat K.S.,
RA Cronin L.A., Shen M., Pai G., Van Aken S., Umayam L., Tallon L.J.,
RA Gill J.E., Adams M.D., Carrera A.J., Creasy T.H., Goodman H.M.,
RA Somerville C.R., Copenhaver G.P., Preuss D., Nierman W.C., White O.,
RA Eisen J.A., Salzberg S.L., Fraser C.M., Venter J.C.;
RT "Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana.";
RL Nature 402:761-768(1999).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=7780305; DOI=10.2307/3870112;
RA Enjuto M., Lumbreras V., Marin C., Boronat A.;
RT "Expression of the Arabidopsis HMG2 gene, encoding 3-hydroxy-3-
RT methylglutaryl coenzyme A reductase, is restricted to meristematic and
RT floral tissues.";
RL Plant Cell 7:517-527(1995).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14871314; DOI=10.1111/j.1365-313x.2004.02003.x;
RA Suzuki M., Kamide Y., Nagata N., Seki H., Ohyama K., Kato H., Masuda K.,
RA Sato S., Kato T., Tabata S., Yoshida S., Muranaka T.;
RT "Loss of function of 3-hydroxy-3-methylglutaryl coenzyme A reductase 1
RT (HMG1) in Arabidopsis leads to dwarfing, early senescence and male
RT sterility, and reduced sterol levels.";
RL Plant J. 37:750-761(2004).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17917299; DOI=10.1248/cpb.55.1518;
RA Ohyama K., Suzuki M., Masuda K., Yoshida S., Muranaka T.;
RT "Chemical phenotypes of the hmg1 and hmg2 mutants of Arabidopsis
RT demonstrate the in-planta role of HMG-CoA reductase in triterpene
RT biosynthesis.";
RL Chem. Pharm. Bull. 55:1518-1521(2007).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=19363204; DOI=10.1093/jxb/erp073;
RA Suzuki M., Nakagawa S., Kamide Y., Kobayashi K., Ohyama K.,
RA Hashinokuchi H., Kiuchi R., Saito K., Muranaka T., Nagata N.;
RT "Complete blockage of the mevalonate pathway results in male gametophyte
RT lethality.";
RL J. Exp. Bot. 60:2055-2064(2009).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, AND INDUCTION.
RX PubMed=19041104; DOI=10.1016/j.phytochem.2008.10.010;
RA Nieto B., Fores O., Arro M., Ferrer A.;
RT "Arabidopsis 3-hydroxy-3-methylglutaryl-CoA reductase is regulated at the
RT post-translational level in response to alterations of the sphingolipid and
RT the sterol biosynthetic pathways.";
RL Phytochemistry 70:53-59(2009).
CC -!- FUNCTION: Catalyzes the synthesis of mevalonate. The specific precursor
CC of all isoprenoid compounds present in plants.
CC {ECO:0000269|PubMed:14871314, ECO:0000269|PubMed:17917299,
CC ECO:0000269|PubMed:19041104, ECO:0000269|PubMed:19363204}.
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 -!- ACTIVITY REGULATION: Regulated at the post-translational level in
CC response to alterations of the sphingolipid and the sterol biosynthetic
CC pathways. {ECO:0000269|PubMed:19041104}.
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:8302869}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:8302869}.
CC -!- TISSUE SPECIFICITY: Restricted to young seedlings, roots, and
CC inflorescences. Expressed in root tips, shoot apex, secretory zone of
CC the stigma, microspores, mature pollen grains, gynoecium vascular
CC tissue and fertilized ovules. {ECO:0000269|PubMed:19363204,
CC ECO:0000269|PubMed:7780305, ECO:0000269|PubMed:8302869}.
CC -!- INDUCTION: Not regulated by myriocin, squalestatin or terbinafine.
CC {ECO:0000269|PubMed:19041104}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype under normal growth
CC conditions, but 25% lower levels in triterpenoids content and 15% lower
CC levels in sterol content. Hmg1 and hmg2 double mutants are lethal
CC during male gametophyte development. {ECO:0000269|PubMed:14871314,
CC ECO:0000269|PubMed:17917299, ECO:0000269|PubMed:19363204}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; L19262; AAA67317.1; -; Genomic_DNA.
DR EMBL; CP002685; AEC06618.1; -; Genomic_DNA.
DR EMBL; AY057680; AAL15311.1; -; mRNA.
DR EMBL; AY143930; AAN28869.1; -; mRNA.
DR PIR; D84551; D84551.
DR RefSeq; NP_179329.1; NM_127292.3.
DR AlphaFoldDB; P43256; -.
DR SMR; P43256; -.
DR BioGRID; 1601; 1.
DR STRING; 3702.AT2G17370.1; -.
DR PaxDb; P43256; -.
DR PRIDE; P43256; -.
DR ProteomicsDB; 230355; -.
DR EnsemblPlants; AT2G17370.1; AT2G17370.1; AT2G17370.
DR GeneID; 816244; -.
DR Gramene; AT2G17370.1; AT2G17370.1; AT2G17370.
DR KEGG; ath:AT2G17370; -.
DR Araport; AT2G17370; -.
DR TAIR; locus:2827622; AT2G17370.
DR eggNOG; KOG2480; Eukaryota.
DR HOGENOM; CLU_001734_2_2_1; -.
DR InParanoid; P43256; -.
DR OMA; DDKMTRA; -.
DR OrthoDB; 907394at2759; -.
DR PhylomeDB; P43256; -.
DR UniPathway; UPA00058; UER00103.
DR PRO; PR:P43256; -.
DR Proteomes; UP000006548; Chromosome 2.
DR ExpressionAtlas; P43256; baseline and differential.
DR Genevisible; P43256; AT.
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:0043231; C:intracellular membrane-bounded organelle; IDA:TAIR.
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: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; IMP:TAIR.
DR GO; GO:0016104; P:triterpenoid biosynthetic process; IMP:TAIR.
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 Endoplasmic reticulum; Glycoprotein; Isoprene biosynthesis; Membrane; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..562
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase 2"
FT /id="PRO_0000114434"
FT TRANSMEM 32..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 101..146
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 147..562
FT /note="Catalytic"
FT /evidence="ECO:0000250"
FT ACT_SITE 240
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 372
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 448
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 544
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT MOD_RES 550
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14891"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 304
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 548
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 562 AA; 60715 MW; A4BF6BE6796C940A CRC64;
MEDLRRRFPT KKNGEEISNV AVDPPLRKAS DALPLPLYLT NTFFLSLFFA TVYFLLSRWR
EKIRNSTPLH VVDLSEICAL IGFVASFIYL LGFCGIDLIF RSSSDDDVWV NDGMIPCNQS
LDCREVLPIK PNSVDPPRES ELDSVEDEEI VKLVIDGTIP SYSLETKLGD CKRAAAIRRE
AVQRITGKSL TGLPLEGFDY NSILGQCCEM PVGYVQIPVG IAGPLLLDGV EYSVPMATTE
GCLVASTNRG FKAIHLSGGA FSVLVKDAMT RAPVVRFPSA RRAALVMFYL QDPSNFERLS
LIFNKSSRFA RLQSITCTIA GRNLYPRFAC STGDAMGMNM VSKGVQNVLD FVKSEFPDMD
VIGISGNYCS DKKASAVNWI EGRGKHVVCE AFIKAEIVEK VLKTSVEALV ELNTLKNLVG
SAMAGSLGGF NAHSSNIVSA VFIATGQDPA QNVESSHCMT MILPDGDDLH ISVSMPCIEV
GTVGGGTQLA SQAACLNLLG VKGSNNEKPG SNAQQLARIV AGSVLAGELS LMSAIAAGQL
VKSHMKYNRS SRDIGPSSQV NR
