Reviewed, UniProtKB/Swiss-Prot P09610 (HMDH_MESAU)

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

Organism

Mesocricetus auratus (Golden hamster)

Taxonomic identifier

10036 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Cricetidae › Cricetinae › Mesocricetus

Protein attributes

Sequence length	887 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis.
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.
Pathway	Metabolic intermediate biosynthesis; mevalonic acid biosynthesis; (R)-mevalonic acid from acetyl-CoA: step 3/3.
Subunit structure	Homodimer.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the HMG-CoA reductase family.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Domain	Transmembrane
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW coenzyme A metabolic process Inferred from electronic annotation. Source: InterPro isoprenoid biosynthetic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
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 – 887	887	3-hydroxy-3-methylglutaryl-coenzyme A reductase		PRO_0000114420
Regions
	Transmembrane	10 – 39	30	Potential
	Transmembrane	57 – 78	22	Potential
	Transmembrane	90 – 114	25	Potential
	Transmembrane	124 – 149	26	Potential
	Transmembrane	160 – 187	28	Potential
	Transmembrane	192 – 220	29	Potential
	Transmembrane	315 – 339	25	Potential
	Region	340 – 449	110	Linker
	Region	450 – 887	438	Catalytic
Sites
	Active site	558	1	Charge relay system By similarity
	Active site	690	1	Charge relay system By similarity
	Active site	766	1	Charge relay system By similarity
	Active site	865	1	Proton donor By similarity
Amino acid modifications
	Glycosylation	281	1	N-linked (GlcNAc...) Potential
	Glycosylation	517	1	N-linked (GlcNAc...) Potential
	Glycosylation	869	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	474	1	H → Q: No loss of activity. Ref.2
	Mutagenesis	487	1	H → Q: No loss of activity. Ref.2
	Mutagenesis	558	1	E → D or Q: Loss of activity. Ref.2
	Mutagenesis	751	1	H → Q: No loss of activity. Ref.2
	Mutagenesis	766	1	D → N: Loss of activity. Ref.2
	Mutagenesis	860	1	H → Q: No loss of activity. Ref.2
	Mutagenesis	865	1	H → K or Q: Loss of activity. Ref.2
	Mutagenesis	868	1	H → Y: No loss of activity. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P09610-1 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: BC6F9D1F8CAD5EA5	FASTA	887	96,955
	10 20 30 40 50 60 MLSRLFRMHG LFVASHPWEV IVGTVTLTIC MMSMNMFTGN NKICGWNYEC PKFEEDVLSS 70 80 90 100 110 120 DIIILTITRC IAILYIYFQF QNLRQLGSKY ILGIAGLFTI FSSFVFSTVV IHFLDKELTG 130 140 150 160 170 180 LNEALPFFLL LIDLSRASAL AKFALSSNSQ DEVRENIARG MAILGPTFTL DALVECLVIG 190 200 210 220 230 240 VGTMSGVRQL EIMCCFGCMS VLANYFVFMT FFPACVSLVL ELSRESREGR PIWQLSHFAR 250 260 270 280 290 300 VLEEEENKPN PVTQRVKMIM SLGLVLVHAH SRWIADPSPQ NSTTEHSKVS LGLDEDVSKR 310 320 330 340 350 360 IEPSVSLWQF YLSKMISMDI EQVVTLSLAF LLAVKYIFFE QAETESTLSL KNPITSPVAT 370 380 390 400 410 420 PKKAPDNCCR REPVLSRRNE KLSSVEEEPG VNQDRKVEVI KPLVAETEST SRATFVLGAS 430 440 450 460 470 480 GGCSPVALGT QEPEIELPSE PRPNEECLQI LESAEKGAKF LSDAEIIQLV NAKHIPAYKL 490 500 510 520 530 540 ETLMETHERG VSIRRQLLST KLPEPSSLQY LPYRDYNYSL VMGACCENVI GYMPIPVGVA 550 560 570 580 590 600 GPLCLDGKEY QVPMATTEGC LVASTNRGCR AIGLGGGASS RVLADGMTRG PVVRLPRACD 610 620 630 640 650 660 SAEVKAWLET PEGFAVIKDA FDSTSRFARL QKLHVTMAGR NLYIRFQSKT GDAMGMNMIS 670 680 690 700 710 720 KGTEKALVKL QEFFPEMQIL AVSGNYCTDK KPAAVNWIEG RGKTVVCEAV IPARVVREVL 730 740 750 760 770 780 KTTTEAMIDV NINKNLVGSA MAGSIGGYNA HAANIVTAIY IACGQDAAQN VGSSNCITLM 790 800 810 820 830 840 EASGPTNEDL YISCTMPSIE IGTVGGGTNL LPQQACLQML GVQGACKDNP GENARQLARI 850 860 870 880 VCGTVMAGEL SLMAALAAGH LVRSHMVHNR SKINLQDLQG TCTKKAA

References

[1]	"The nucleotide sequence of Syrian hamster HMG-CoA reductase cDNA." Skalnik D.G., Simoni R.D. DNA 4:439-444(1985) [PubMed: 3841506] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"His865 is the catalytically important histidyl residue of Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase." Darnay B.G., Rodwell V.W. J. Biol. Chem. 268:8429-8435(1993) [PubMed: 8473286] [Abstract] Cited for: MUTAGENESIS OF HISTIDINE RESIDUES.
[3]	"The active site of hamster 3-hydroxy-3-methylglutaryl-CoA reductase resides at the subunit interface and incorporates catalytically essential acidic residues from separate polypeptides." Frimpong K., Rodwell V.W. J. Biol. Chem. 269:1217-1221(1994) [PubMed: 8288583] [Abstract] Cited for: MUTAGENESIS.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M12705 mRNA. Translation: AAA37077.1.
PIR	A23586.
3D structure databases
HSSP	HSSP built from PDB template 1HWJ based on UniProtKB P04035.
SMR	P09610. Positions 461-869.
ModBase	Search...
Phylogenomic databases
HOVERGEN	P09610.
Enzyme and pathway databases
BRENDA	1.1.1.34. 824.
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...

Entry information

Entry name

HMDH_MESAU

Accession

Primary (citable) accession number: P09610

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	June 16, 2009
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)