HMDH_DROME
ID HMDH_DROME Reviewed; 920 AA.
AC P14773; A4V3A8; Q9VCI8;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE Short=HMG-CoA reductase;
DE EC=1.1.1.34;
GN Name=Hmgcr; Synonyms=HmG-CoAR; ORFNames=CG10367;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ACTIVITY REGULATION.
RX PubMed=3136321; DOI=10.1128/mcb.8.7.2713-2721.1988;
RA Gertler F.B., Chiu C.-Y., Richter-Mann L., Chin D.J.;
RT "Developmental and metabolic regulation of the Drosophila melanogaster 3-
RT hydroxy-3-methylglutaryl coenzyme A reductase.";
RL Mol. Cell. Biol. 8:2713-2721(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=9853754; DOI=10.1038/24871;
RA Van Doren M., Broihier H.T., Moore L.A., Lehmann R.;
RT "HMG-CoA reductase guides migrating primordial germ cells.";
RL Nature 396:466-469(1998).
CC -!- FUNCTION: Synthesis of mevalonate for the production of non-sterol
CC isoprenoids, which are essential for growth differentiation. Provides
CC spatial information during embryogenesis to guide migrating primordial
CC germ cells (the pole cells) from the ectoderm to the mesoderm. Also
CC required for association of the pole cells with the gonadal mesoderm.
CC {ECO:0000269|PubMed:9853754}.
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: The activity of HMG-CoA-reductase is suppressed by
CC exogenous mevalonate. {ECO:0000269|PubMed:3136321}.
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 -!- TISSUE SPECIFICITY: Highly expressed in embryonic gonadal mesoderm,
CC where expression is initially broad, and then becomes restricted to a
CC segmental pattern at stage 11. Expression is then further restricted to
CC a cluster of cells in each of parasegments 10, 11 and 12, corresponding
CC to the developing gonadal mesoderm. Not expressed in pole cells.
CC {ECO:0000269|PubMed:9853754}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; M21329; AAA28608.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF56175.1; -; Genomic_DNA.
DR EMBL; AE014297; AAS65198.1; -; Genomic_DNA.
DR PIR; S32572; S32572.
DR RefSeq; NP_732900.1; NM_170089.2.
DR AlphaFoldDB; P14773; -.
DR SMR; P14773; -.
DR BioGRID; 67741; 9.
DR IntAct; P14773; 1.
DR STRING; 7227.FBpp0083842; -.
DR GlyGen; P14773; 9 sites.
DR PaxDb; P14773; -.
DR PRIDE; P14773; -.
DR EnsemblMetazoa; FBtr0084450; FBpp0083842; FBgn0263782.
DR GeneID; 42803; -.
DR KEGG; dme:Dmel_CG10367; -.
DR CTD; 3156; -.
DR FlyBase; FBgn0263782; Hmgcr.
DR VEuPathDB; VectorBase:FBgn0263782; -.
DR eggNOG; KOG2480; Eukaryota.
DR GeneTree; ENSGT00940000155305; -.
DR HOGENOM; CLU_001734_0_1_1; -.
DR InParanoid; P14773; -.
DR OMA; CHGWSQS; -.
DR OrthoDB; 907394at2759; -.
DR PhylomeDB; P14773; -.
DR Reactome; R-DME-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00058; UER00103.
DR BioGRID-ORCS; 42803; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 42803; -.
DR PRO; PR:P14773; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0263782; Expressed in fat body/gonad primordium (Drosophila) and 44 other tissues.
DR ExpressionAtlas; P14773; baseline and differential.
DR Genevisible; P14773; DM.
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; ISS:FlyBase.
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:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0018990; P:ecdysis, chitin-based cuticle; IMP:FlyBase.
DR GO; GO:0035050; P:embryonic heart tube development; IMP:FlyBase.
DR GO; GO:0035232; P:germ cell attraction; IDA:FlyBase.
DR GO; GO:0008354; P:germ cell migration; IMP:FlyBase.
DR GO; GO:0008406; P:gonad development; TAS:FlyBase.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0007626; P:locomotory behavior; IMP:FlyBase.
DR GO; GO:0007280; P:pole cell migration; IMP:UniProtKB.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; HGI:FlyBase.
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 Endoplasmic reticulum; Glycoprotein; Isoprene biosynthesis; Membrane; NADP;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..920
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114431"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..129
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 208..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..257
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 364..384
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 106..263
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 62..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..498
FT /note="Linker"
FT REGION 499..829
FT /note="Catalytic"
FT COMPBIAS 63..85
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 586
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 717
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 793
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 892
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 346
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 443
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 475
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 797
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 802
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 896
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 910
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 4
FT /note="R -> P (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 9..11
FT /note="HGE -> TQ (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 33..49
FT /note="TVDKNNTLDASSGLGTA -> NGGQEQYPGCEQRIGHS (in Ref. 1;
FT AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="Missing (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 186..191
FT /note="AQLALS -> RSGAM (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="E -> V (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 286
FT /note="L -> P (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 321..330
FT /note="VAFSGSDYDA -> EVSPAATTM (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="A -> E (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 680
FT /note="A -> R (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
FT CONFLICT 689..700
FT /note="GAEMALRRIQLQ -> ALRWPFAEFTLH (in Ref. 1; AAA28608)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 920 AA; 98317 MW; C2E3959EAF339841 CRC64;
MIGRLFRAHG EFCASHPWEV IVALLTITAC MLTVDKNNTL DASSGLGTAT ASAAAAGGSG
SGAGSGASGT IPPSSMGGSA TSSRHRPCHG WSQSCDGLEA EYNAADVILM TIVRCTAVLY
CYYQFCSLHR LGSKYVLGIA GLFTVFSSFI FTTAIIKFLG SDISELKDAL FFLLLVIDLS
NSGRLAQLAL SGSNQAEVTQ NIARGLELLG PAISLDTIVE VLLVGVGTLS GVQRLEVLCM
FAVLSVLVNY VVFMTFYPAC LSLIFDLSRS GVDMSVVREK AKGSLLLKSL TEEEQKANPV
LQRVKLIMTT GLMAVHIYSR VAFSGSDYDA VDKTLTPTLS LNVSNNRTES GEIADIIIKW
LTMSADHIVI SIVLIALVVK FICFDNRDPL PDQLRQSGPV AIAAKASQTT PIDEEHVEQE
KDTENSAAVR TLLFTIEDQS SANASTQTDL LPLRHRLVGP IKPPRPVQEC LDILNSTEEG
SGPAALSDEE IVSIVHAGGT HCPLHKIESV LDDPERGVRI RRQIIGSRAK MPVGRLDVLP
YEHFDYRKVL NACCENVLGY VPIPVGYAGP LLLDGETYYV PMATTEGALV ASTNRGCKAL
SVRGVRSVVE DVGMTRAPCV RFPSVARAAE AKSWIENDEN YRVVKTEFDS TSRFGRLKDC
HIAMDGPQLY IRFVAITGDA MGMNMVSKGA EMALRRIQLQ FPDMQIISLS GNFCCDKKPA
AINWIKGRGK RVVTECTISA ATLRSVLKTD AKTLVECNKL KNMGGSAMAG SIGGNNAHAA
NMVTAVFLAT GQDPAQNVTS SNCSTAMECW AENSEDLYMT CTMPSLEVGT VGGGTGLPGQ
SACLEMLGVR GAHATRPGDN AKKLAQIVCA TVMAGELSLM AALVNSDLVK SHMRHNRSSI
AVNSANNPLN VTVSSCSTIS
