Reviewed, UniProtKB/Swiss-Prot P14773 (HMDH_DROME)

Names and origin

Protein names

Recommended name:
    3-hydroxy-3-methylglutaryl-coenzyme A reductase
      Short name=HMG-CoA reductase
    EC=1.1.1.34

Gene names

Name:	Hmgcr
Synonyms:	HmG-CoAR
ORF Names:	CG10367

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	920 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	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. Ref.4
Catalytic activity	(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH.
Enzyme regulation	The activity of HMG-CoA-reductase is suppressed by exogenous mevalonate. Ref.1
Pathway	Metabolic intermediate biosynthesis; mevalonic acid biosynthesis; (R)-mevalonic acid from acetyl-CoA: step 3/3.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein.
Tissue specificity	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. Ref.4
Sequence similarities	Belongs to the HMG-CoA reductase family. Contains 1 SSD (sterol-sensing) domain.

Ontologies

Keywords
Biological process	Isoprene biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Domain	Transmembrane
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	coenzyme A metabolic process Inferred from electronic annotation. Source: InterPro embryonic heart tube development Inferred from mutant phenotype. Source: FlyBase germ cell attraction Traceable author statement. Source: FlyBase gonad development Traceable author statement. Source: FlyBase isoprenoid biosynthetic process Traceable author statement. Source: FlyBase oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW pole cell migration Ref.4 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	NADP or NADPH binding Inferred from electronic annotation. Source: InterPro hydroxymethylglutaryl-CoA reductase (NADPH) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 920	920	3-hydroxy-3-methylglutaryl-coenzyme A reductase		PRO_0000114431
Regions
	Transmembrane	12 – 32	21	Potential
	Transmembrane	107 – 129	23	Potential
	Transmembrane	136 – 156	21	Potential
	Transmembrane	170 – 190	21	Potential
	Transmembrane	208 – 228	21	Potential
	Transmembrane	237 – 257	21	Potential
	Transmembrane	364 – 384	21	Potential
	Domain	106 – 263	158	SSD
	Region	385 – 498	114	Linker
	Region	499 – 829	331	Catalytic
Sites
	Active site	586	1	Charge relay system By similarity
	Active site	717	1	Charge relay system By similarity
	Active site	793	1	Charge relay system By similarity
	Active site	892	1	Proton donor By similarity
Amino acid modifications
	Glycosylation	37	1	N-linked (GlcNAc...) Potential
	Glycosylation	342	1	N-linked (GlcNAc...) Potential
	Glycosylation	346	1	N-linked (GlcNAc...) Potential
	Glycosylation	443	1	N-linked (GlcNAc...) Potential
	Glycosylation	475	1	N-linked (GlcNAc...) Potential
	Glycosylation	797	1	N-linked (GlcNAc...) Potential
	Glycosylation	802	1	N-linked (GlcNAc...) Potential
	Glycosylation	896	1	N-linked (GlcNAc...) Potential
	Glycosylation	910	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	4	1	R → P in AAA28608. Ref.1
	Sequence conflict	9 – 11	3	HGE → TQ in AAA28608. Ref.1
	Sequence conflict	33 – 49	17	TVDKN…GLGTA → NGGQEQYPGCEQRIGHS in AAA28608. Ref.1
	Sequence conflict	58	1	Missing in AAA28608. Ref.1
	Sequence conflict	186 – 191	6	AQLALS → RSGAM in AAA28608. Ref.1
	Sequence conflict	220	1	E → V in AAA28608. Ref.1
	Sequence conflict	286	1	L → P in AAA28608. Ref.1
	Sequence conflict	321 – 330	10	VAFSGSDYDA → EVSPAATTM in AAA28608. Ref.1
	Sequence conflict	403	1	A → E in AAA28608. Ref.1
	Sequence conflict	680	1	A → R in AAA28608. Ref.1
	Sequence conflict	689 – 700	12	GAEMA…RIQLQ → ALRWPFAEFTLH in AAA28608. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P14773-1 [UniParc]. Last modified May 24, 2005. Version 2. Checksum: C2E3959EAF339841	FASTA	920	98,317
	10 20 30 40 50 60 MIGRLFRAHG EFCASHPWEV IVALLTITAC MLTVDKNNTL DASSGLGTAT ASAAAAGGSG 70 80 90 100 110 120 SGAGSGASGT IPPSSMGGSA TSSRHRPCHG WSQSCDGLEA EYNAADVILM TIVRCTAVLY 130 140 150 160 170 180 CYYQFCSLHR LGSKYVLGIA GLFTVFSSFI FTTAIIKFLG SDISELKDAL FFLLLVIDLS 190 200 210 220 230 240 NSGRLAQLAL SGSNQAEVTQ NIARGLELLG PAISLDTIVE VLLVGVGTLS GVQRLEVLCM 250 260 270 280 290 300 FAVLSVLVNY VVFMTFYPAC LSLIFDLSRS GVDMSVVREK AKGSLLLKSL TEEEQKANPV 310 320 330 340 350 360 LQRVKLIMTT GLMAVHIYSR VAFSGSDYDA VDKTLTPTLS LNVSNNRTES GEIADIIIKW 370 380 390 400 410 420 LTMSADHIVI SIVLIALVVK FICFDNRDPL PDQLRQSGPV AIAAKASQTT PIDEEHVEQE 430 440 450 460 470 480 KDTENSAAVR TLLFTIEDQS SANASTQTDL LPLRHRLVGP IKPPRPVQEC LDILNSTEEG 490 500 510 520 530 540 SGPAALSDEE IVSIVHAGGT HCPLHKIESV LDDPERGVRI RRQIIGSRAK MPVGRLDVLP 550 560 570 580 590 600 YEHFDYRKVL NACCENVLGY VPIPVGYAGP LLLDGETYYV PMATTEGALV ASTNRGCKAL 610 620 630 640 650 660 SVRGVRSVVE DVGMTRAPCV RFPSVARAAE AKSWIENDEN YRVVKTEFDS TSRFGRLKDC 670 680 690 700 710 720 HIAMDGPQLY IRFVAITGDA MGMNMVSKGA EMALRRIQLQ FPDMQIISLS GNFCCDKKPA 730 740 750 760 770 780 AINWIKGRGK RVVTECTISA ATLRSVLKTD AKTLVECNKL KNMGGSAMAG SIGGNNAHAA 790 800 810 820 830 840 NMVTAVFLAT GQDPAQNVTS SNCSTAMECW AENSEDLYMT CTMPSLEVGT VGGGTGLPGQ 850 860 870 880 890 900 SACLEMLGVR GAHATRPGDN AKKLAQIVCA TVMAGELSLM AALVNSDLVK SHMRHNRSSI 910 920 AVNSANNPLN VTVSSCSTIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Developmental and metabolic regulation of the Drosophila melanogaster 3-hydroxy-3-methylglutaryl coenzyme A reductase." Gertler F.B., Chiu C.-Y., Richter-Mann L., Chin D.J. Mol. Cell. Biol. 8:2713-2721(1988) [PubMed: 3136321] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ENZYME REGULATION.
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[4]	"HMG-CoA reductase guides migrating primordial germ cells." Van Doren M., Broihier H.T., Moore L.A., Lehmann R. Nature 396:466-469(1998) [PubMed: 9853754] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M21329 Genomic DNA. Translation: AAA28608.1. AE014297 Genomic DNA. Translation: AAF56175.1. AE014297 Genomic DNA. Translation: AAS65198.1.
PIR	S32572.
RefSeq	NP_732900.1. NP_996271.1.
UniGene	Dm.21259
3D structure databases
HSSP	HSSP built from PDB template 1HW8 based on UniProtKB P04035.
ModBase	Search...
Genome annotation databases
Ensembl	FBgn0001205. Drosophila melanogaster. [Contig view]
GeneID	42803.
KEGG	dme:Dmel_CG10367.
Organism-specific databases
FlyBase	FBgn0001205. Hmgcr.
Phylogenomic databases
HOGENOM	P14773.
OMA	P14773. GAKFLSD.
Enzyme and pathway databases
BRENDA	1.1.1.34. 48.
Gene expression databases
ArrayExpress	P14773.
GermOnline	CG10367. Drosophila melanogaster.
Family and domain databases
InterPro	IPR002202. HMG_CoA_Rdtase_cat. IPR004554. HMG_CoA_Rdtase_I_cat. IPR004816. HMG_CoA_Rdtase_I_metazoan. IPR000731. SSD_5TM. [Graphical view]
Gene3D	G3DSA:3.90.770.10. HMG-CoA_red. 1 hit.
PANTHER	PTHR10572. HMG-CoA_red. 1 hit.
Pfam	PF00368. HMG-CoA_red. 1 hit. [Graphical view]
PRINTS	PR00071. HMGCOARDTASE.
TIGRFAMs	TIGR00920. 2A060605. 1 hit. TIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITE	PS00066. 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]
ProtoNet	Search...
Other Resources
NextBio	830648.

Entry information

Entry name

HMDH_DROME

Accession

Primary (citable) accession number: P14773
Secondary accession number(s): A4V3A8, Q9VCI8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	May 24, 2005
Last modified:	June 16, 2009
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project