Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

3-hydroxy-3-methylglutaryl-coenzyme A reductase

Gene

Hmgcr

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Synthesis of mevalonate for the production of non-sterol isoprenoids, which are essential for growth differentiation. Provides spatial information during embryogenesis to guide migrating primordial germ cells (the pole cells) from the ectoderm to the mesoderm. Also required for association of the pole cells with the gonadal mesoderm.1 Publication

Catalytic activityi

(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH.PROSITE-ProRule annotation

Enzyme regulationi

The activity of HMG-CoA-reductase is suppressed by exogenous mevalonate.1 Publication

Pathwayi: (R)-mevalonate biosynthesis

This protein is involved in step 3 of the subpathway that synthesizes (R)-mevalonate from acetyl-CoA.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. no protein annotated in this organism
  2. no protein annotated in this organism
  3. 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr), 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr-RA), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr)
This subpathway is part of the pathway (R)-mevalonate biosynthesis, which is itself part of Metabolic intermediate biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-mevalonate from acetyl-CoA, the pathway (R)-mevalonate biosynthesis and in Metabolic intermediate biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei586 – 5861Charge relay systemBy similarity
Active sitei717 – 7171Charge relay systemBy similarity
Active sitei793 – 7931Charge relay systemBy similarity
Active sitei892 – 8921Proton donorPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • coenzyme A metabolic process Source: InterPro
  • ecdysis, chitin-based cuticle Source: FlyBase
  • embryonic heart tube development Source: FlyBase
  • germ cell attraction Source: FlyBase
  • germ cell migration Source: FlyBase
  • gonad development Source: FlyBase
  • isoprenoid biosynthetic process Source: FlyBase
  • locomotory behavior Source: FlyBase
  • pole cell migration Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: FlyBase
  • positive regulation of Ras protein signal transduction Source: FlyBase
  • sterol biosynthetic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Isoprene biosynthesis

Keywords - Ligandi

NADP

Enzyme and pathway databases

ReactomeiR-DME-191273. Cholesterol biosynthesis.
UniPathwayiUPA00058; UER00103.

Names & Taxonomyi

Protein namesi
Recommended name:
3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC:1.1.1.34)
Short name:
HMG-CoA reductase
Gene namesi
Name:Hmgcr
Synonyms:HmG-CoAR
ORF Names:CG10367
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 3R

Organism-specific databases

FlyBaseiFBgn0263782. Hmgcr.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei12 – 3221HelicalSequence analysisAdd
BLAST
Transmembranei107 – 12923HelicalSequence analysisAdd
BLAST
Transmembranei136 – 15621HelicalSequence analysisAdd
BLAST
Transmembranei170 – 19021HelicalSequence analysisAdd
BLAST
Transmembranei208 – 22821HelicalSequence analysisAdd
BLAST
Transmembranei237 – 25721HelicalSequence analysisAdd
BLAST
Transmembranei364 – 38421HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: GO_Central
  • integral component of membrane Source: UniProtKB-KW
  • intracellular Source: FlyBase
  • peroxisomal membrane Source: FlyBase
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 9209203-hydroxy-3-methylglutaryl-coenzyme A reductasePRO_0000114431Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi37 – 371N-linked (GlcNAc...)Sequence analysis
Glycosylationi342 – 3421N-linked (GlcNAc...)Sequence analysis
Glycosylationi346 – 3461N-linked (GlcNAc...)Sequence analysis
Glycosylationi443 – 4431N-linked (GlcNAc...)Sequence analysis
Glycosylationi475 – 4751N-linked (GlcNAc...)Sequence analysis
Glycosylationi797 – 7971N-linked (GlcNAc...)Sequence analysis
Glycosylationi802 – 8021N-linked (GlcNAc...)Sequence analysis
Glycosylationi896 – 8961N-linked (GlcNAc...)Sequence analysis
Glycosylationi910 – 9101N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP14773.
PRIDEiP14773.

Expressioni

Tissue specificityi

Highly expressed in embryonic gonadal mesoderm, where expression is initially broad, and then becomes restricted to a segmental pattern at stage 11. Expression is then further restricted to a cluster of cells in each of parasegments 10, 11 and 12, corresponding to the developing gonadal mesoderm. Not expressed in pole cells.1 Publication

Gene expression databases

BgeeiFBgn0263782.
GenevisibleiP14773. DM.

Interactioni

Protein-protein interaction databases

BioGridi67741. 1 interaction.
IntActiP14773. 1 interaction.
STRINGi7227.FBpp0083842.

Structurei

3D structure databases

ProteinModelPortaliP14773.
SMRiP14773. Positions 486-883.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini106 – 263158SSDPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni385 – 498114LinkerAdd
BLAST
Regioni499 – 829331CatalyticAdd
BLAST

Sequence similaritiesi

Belongs to the HMG-CoA reductase family.Curated
Contains 1 SSD (sterol-sensing) domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2480. Eukaryota.
COG1257. LUCA.
GeneTreeiENSGT00840000129910.
InParanoidiP14773.
KOiK00021.
OMAiPNEECLQ.
OrthoDBiEOG091G0I1B.
PhylomeDBiP14773.

Family and domain databases

CDDicd00643. HMG-CoA_reductase_classI. 1 hit.
Gene3Di1.10.3270.10. 1 hit.
3.30.70.420. 1 hit.
3.90.770.10. 2 hits.
InterProiIPR002202. HMG_CoA_Rdtase.
IPR023074. HMG_CoA_Rdtase_cat.
IPR023076. HMG_CoA_Rdtase_CS.
IPR004554. HMG_CoA_Rdtase_eu_arc.
IPR004816. HMG_CoA_Rdtase_metazoan.
IPR023282. HMG_CoA_Rdtase_N.
IPR009023. HMG_CoA_Rdtase_NAD(P)-bd_dom.
IPR009029. HMG_CoA_Rdtase_sub-bd_dom.
IPR000731. SSD.
[Graphical view]
PANTHERiPTHR10572. PTHR10572. 2 hits.
PfamiPF00368. HMG-CoA_red. 1 hit.
PF12349. Sterol-sensing. 1 hit.
[Graphical view]
PRINTSiPR00071. HMGCOARDTASE.
SUPFAMiSSF55035. SSF55035. 1 hit.
SSF56542. SSF56542. 2 hits.
TIGRFAMsiTIGR00920. 2A060605. 1 hit.
TIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITEiPS00066. HMG_COA_REDUCTASE_1. 1 hit.
PS00318. HMG_COA_REDUCTASE_2. 1 hit.
PS01192. HMG_COA_REDUCTASE_3. 1 hit.
PS50065. HMG_COA_REDUCTASE_4. 1 hit.
PS50156. SSD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P14773-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIGRLFRAHG EFCASHPWEV IVALLTITAC MLTVDKNNTL DASSGLGTAT
60 70 80 90 100
ASAAAAGGSG SGAGSGASGT IPPSSMGGSA TSSRHRPCHG WSQSCDGLEA
110 120 130 140 150
EYNAADVILM TIVRCTAVLY CYYQFCSLHR LGSKYVLGIA GLFTVFSSFI
160 170 180 190 200
FTTAIIKFLG SDISELKDAL FFLLLVIDLS NSGRLAQLAL SGSNQAEVTQ
210 220 230 240 250
NIARGLELLG PAISLDTIVE VLLVGVGTLS GVQRLEVLCM FAVLSVLVNY
260 270 280 290 300
VVFMTFYPAC LSLIFDLSRS GVDMSVVREK AKGSLLLKSL TEEEQKANPV
310 320 330 340 350
LQRVKLIMTT GLMAVHIYSR VAFSGSDYDA VDKTLTPTLS LNVSNNRTES
360 370 380 390 400
GEIADIIIKW LTMSADHIVI SIVLIALVVK FICFDNRDPL PDQLRQSGPV
410 420 430 440 450
AIAAKASQTT PIDEEHVEQE KDTENSAAVR TLLFTIEDQS SANASTQTDL
460 470 480 490 500
LPLRHRLVGP IKPPRPVQEC LDILNSTEEG SGPAALSDEE IVSIVHAGGT
510 520 530 540 550
HCPLHKIESV LDDPERGVRI RRQIIGSRAK MPVGRLDVLP YEHFDYRKVL
560 570 580 590 600
NACCENVLGY VPIPVGYAGP LLLDGETYYV PMATTEGALV ASTNRGCKAL
610 620 630 640 650
SVRGVRSVVE DVGMTRAPCV RFPSVARAAE AKSWIENDEN YRVVKTEFDS
660 670 680 690 700
TSRFGRLKDC HIAMDGPQLY IRFVAITGDA MGMNMVSKGA EMALRRIQLQ
710 720 730 740 750
FPDMQIISLS GNFCCDKKPA AINWIKGRGK RVVTECTISA ATLRSVLKTD
760 770 780 790 800
AKTLVECNKL KNMGGSAMAG SIGGNNAHAA NMVTAVFLAT GQDPAQNVTS
810 820 830 840 850
SNCSTAMECW AENSEDLYMT CTMPSLEVGT VGGGTGLPGQ SACLEMLGVR
860 870 880 890 900
GAHATRPGDN AKKLAQIVCA TVMAGELSLM AALVNSDLVK SHMRHNRSSI
910 920
AVNSANNPLN VTVSSCSTIS
Length:920
Mass (Da):98,317
Last modified:May 24, 2005 - v2
Checksum:iC2E3959EAF339841
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti4 – 41R → P in AAA28608 (PubMed:3136321).Curated
Sequence conflicti9 – 113HGE → TQ in AAA28608 (PubMed:3136321).Curated
Sequence conflicti33 – 4917TVDKN…GLGTA → NGGQEQYPGCEQRIGHS in AAA28608 (PubMed:3136321).CuratedAdd
BLAST
Sequence conflicti58 – 581Missing in AAA28608 (PubMed:3136321).Curated
Sequence conflicti186 – 1916AQLALS → RSGAM in AAA28608 (PubMed:3136321).Curated
Sequence conflicti220 – 2201E → V in AAA28608 (PubMed:3136321).Curated
Sequence conflicti286 – 2861L → P in AAA28608 (PubMed:3136321).Curated
Sequence conflicti321 – 33010VAFSGSDYDA → EVSPAATTM in AAA28608 (PubMed:3136321).Curated
Sequence conflicti403 – 4031A → E in AAA28608 (PubMed:3136321).Curated
Sequence conflicti680 – 6801A → R in AAA28608 (PubMed:3136321).Curated
Sequence conflicti689 – 70012GAEMA…RIQLQ → ALRWPFAEFTLH in AAA28608 (PubMed:3136321).CuratedAdd
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21329 Genomic DNA. Translation: AAA28608.1.
AE014297 Genomic DNA. Translation: AAF56175.1.
AE014297 Genomic DNA. Translation: AAS65198.1.
PIRiS32572.
RefSeqiNP_732900.1. NM_170089.2.
UniGeneiDm.21259.

Genome annotation databases

EnsemblMetazoaiFBtr0084450; FBpp0083842; FBgn0263782.
GeneIDi42803.
KEGGidme:Dmel_CG10367.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21329 Genomic DNA. Translation: AAA28608.1.
AE014297 Genomic DNA. Translation: AAF56175.1.
AE014297 Genomic DNA. Translation: AAS65198.1.
PIRiS32572.
RefSeqiNP_732900.1. NM_170089.2.
UniGeneiDm.21259.

3D structure databases

ProteinModelPortaliP14773.
SMRiP14773. Positions 486-883.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi67741. 1 interaction.
IntActiP14773. 1 interaction.
STRINGi7227.FBpp0083842.

Proteomic databases

PaxDbiP14773.
PRIDEiP14773.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0084450; FBpp0083842; FBgn0263782.
GeneIDi42803.
KEGGidme:Dmel_CG10367.

Organism-specific databases

CTDi3156.
FlyBaseiFBgn0263782. Hmgcr.

Phylogenomic databases

eggNOGiKOG2480. Eukaryota.
COG1257. LUCA.
GeneTreeiENSGT00840000129910.
InParanoidiP14773.
KOiK00021.
OMAiPNEECLQ.
OrthoDBiEOG091G0I1B.
PhylomeDBiP14773.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00103.
ReactomeiR-DME-191273. Cholesterol biosynthesis.

Miscellaneous databases

ChiTaRSiHmgcr. fly.
GenomeRNAii42803.
PROiP14773.

Gene expression databases

BgeeiFBgn0263782.
GenevisibleiP14773. DM.

Family and domain databases

CDDicd00643. HMG-CoA_reductase_classI. 1 hit.
Gene3Di1.10.3270.10. 1 hit.
3.30.70.420. 1 hit.
3.90.770.10. 2 hits.
InterProiIPR002202. HMG_CoA_Rdtase.
IPR023074. HMG_CoA_Rdtase_cat.
IPR023076. HMG_CoA_Rdtase_CS.
IPR004554. HMG_CoA_Rdtase_eu_arc.
IPR004816. HMG_CoA_Rdtase_metazoan.
IPR023282. HMG_CoA_Rdtase_N.
IPR009023. HMG_CoA_Rdtase_NAD(P)-bd_dom.
IPR009029. HMG_CoA_Rdtase_sub-bd_dom.
IPR000731. SSD.
[Graphical view]
PANTHERiPTHR10572. PTHR10572. 2 hits.
PfamiPF00368. HMG-CoA_red. 1 hit.
PF12349. Sterol-sensing. 1 hit.
[Graphical view]
PRINTSiPR00071. HMGCOARDTASE.
SUPFAMiSSF55035. SSF55035. 1 hit.
SSF56542. SSF56542. 2 hits.
TIGRFAMsiTIGR00920. 2A060605. 1 hit.
TIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITEiPS00066. HMG_COA_REDUCTASE_1. 1 hit.
PS00318. HMG_COA_REDUCTASE_2. 1 hit.
PS01192. HMG_COA_REDUCTASE_3. 1 hit.
PS50065. HMG_COA_REDUCTASE_4. 1 hit.
PS50156. SSD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHMDH_DROME
AccessioniPrimary (citable) accession number: P14773
Secondary accession number(s): A4V3A8, Q9VCI8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: May 24, 2005
Last modified: September 7, 2016
This is version 160 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.