Reviewed, UniProtKB/Swiss-Prot P00347 (HMDH_CRIGR)

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

Cricetulus griseus (Chinese hamster)

Taxonomic identifier

10029 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	887 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Inferred from homology.

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.
Pathway	Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
Subunit structure	Homodimer By similarity.
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: InterPro integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
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_0000114418
Regions
	Transmembrane	10 – 39	30
	Transmembrane	57 – 78	22
	Transmembrane	90 – 114	25
	Transmembrane	124 – 149	26
	Transmembrane	160 – 187	28
	Transmembrane	192 – 220	29
	Transmembrane	315 – 339	25
	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
Natural variations
	Natural variant	733	1	N → C

Sequences

	Sequence		Length	Mass (Da)
	P00347-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 4331E53ADA250E6A	FASTA	887	97,081
	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 KNPITSPVVT 370 380 390 400 410 420 PKKAPDNCCR REPLLVRRSE KLSSVEEEPG VSQDRKVEVI KPLVVETESA SRATFVLGAS 430 440 450 460 470 480 GTSPPVAART QELEIELPSE 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 KGTEKALLKL QEFFPEMQIL AVSGNYCTDK KPAAINWIEG RGKTVVCEAV IPAKVVREVL 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 TCTKKSA

References

[1]	"Nucleotide sequence of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, a glycoprotein of endoplasmic reticulum." Chin D.J., Gil G., Russell D.W., Liscum L., Luskey K.L., Basu S.K., Okayama H., Berg P., Goldstein J.L., Brown M.S. Nature 308:613-617(1984) [PubMed: 6546784] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions." Reynolds G.A., Basu S.K., Osborne T.F., Chin D.J., Gil G., Brown M.S., Goldstein J.L., Luskey K.L. Cell 38:275-285(1984) [PubMed: 6088070] [Abstract] Cited for: GENE STRUCTURE.
[3]	"Domain structure of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a glycoprotein of the endoplasmic reticulum." Liscum L., Finer-Moore J., Stroud R.M., Luskey K.L., Brown M.S., Goldstein J.L. J. Biol. Chem. 260:522-530(1985) [PubMed: 3965461] [Abstract] Cited for: DOMAINS.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L00183 , L00166, L00169, L00170, L00171, L00173, L00176, L00177, L00178, L00179, L00180, L00181, L00182 Genomic DNA. Translation: AAA36989.1. X00494 Genomic DNA. Translation: CAA25189.1.
PIR	RDHYE. A93328.
3D structure databases
HSSP	HSSP built from PDB template 1HWJ based on UniProtKB P04035.
SMR	P00347. Positions 461-869.
ModBase	Search...
Phylogenomic databases
HOVERGEN	P00347.
Enzyme and pathway databases
BRENDA	1.1.1.34. 18.
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_CRIGR

Accession

Primary (citable) accession number: P00347

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	October 13, 2009
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)