[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Hangjiong C., Williams D., Shapiro D.; "Cloning and sequencing of rat 3-hydroxy-3-methylglutaryl coenzyme A reductase."; Submitted (AUG-1994) to the EMBL/GenBank/DDBJ databases.
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Prostate; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[3]	NUCLEOTIDE SEQUENCE [MRNA] OF 644-887. STRAIN=Sprague-Dawley; TISSUE=Liver; Khan S., Kabat S., Stambrook P.; "Rat HMG-CoA reductase cDNA sequence contains an unusual 36 bp insert bounded by inverted repeats."; Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases.
[4]	PROTEIN SEQUENCE OF 423-443 AND 867-878, AND PHOSPHORYLATION AT SER-871. TISSUE=Liver; PubMed=2369897 [NCBI, ExPASy, EBI, Israel, Japan] Clarke P.R., Hardie D.G.; "Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver."; EMBO J. 9:2439-2446(1990).
[5]	CHARACTERIZATION. TISSUE=Liver; PubMed=4019513 [NCBI, ExPASy, EBI, Israel, Japan] Edwards P.A., Kempner E.S., Lan S.-F., Erickson S.K.; "Functional size of rat hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase as determined by radiation inactivation."; J. Biol. Chem. 260:10278-10282(1985).
[6]	PHOSPHORYLATION. TISSUE=Liver; DOI=10.1016/0014-5793(92)80837-7; PubMed=1628744 [NCBI, ExPASy, EBI, Israel, Japan] Gillespie J.G., Hardie D.G.; "Phosphorylation and inactivation of HMG-CoA reductase at the AMP-activated protein kinase site in response to fructose treatment of isolated rat hepatocytes."; FEBS Lett. 306:59-62(1992).

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; mevalonic acid biosynthesis; (R)-mevalonic acid from acetyl-CoA: step 3/3 .
SUBUNIT: Homodimer.
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein.
SIMILARITY: Belongs to the HMG-CoA reductase family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M29249; AAA40608.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC064654; AAH64654.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X55286; CAA39001.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

S33175; S33175.

NP_037266.2; -.

3D structure databases

HSSP

P04035; 1HWJ. [HSSP ENTRY / PDB]

P51639; 461-869.

PTM databases

P51639; -.

Organism-specific databases

RGD

2803; Hmgcr.

Gene expression databases

ArrayExpress

P51639; -.

GermOnline

ENSRNOG00000016122; Rattus norvegicus.

Ontologies

GO:0006695;	Biological process: cholesterol biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

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 of domain structure.

Gene3D

G3DSA:3.90.770.10; HMG-CoA_red; 1.

PANTHER

PTHR10572; HMG-CoA_red; 1.

Pfam

PF00368; HMG-CoA_red; 1.
Pfam graphical view of domain structure.

PRINTS

PR00071; HMGCOARDTASE.

TIGRFAMs

TIGR00920; 2A060605; 1.
TIGR00533; HMG_CoA_R_NADP; 1.

PROSITE

PS00066; HMG_COA_REDUCTASE_1; 1.
PS00318; HMG_COA_REDUCTASE_2; 1.
PS01192; HMG_COA_REDUCTASE_3; 1.
PS50065; HMG_COA_REDUCTASE_4; 1.
PS50156; SSD; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

Ensembl

ENSRNOG00000016122; Rattus norvegicus. [Contig view]

GeneID

25675; -.

KEGG

rno:25675; -.

NMPDR

fig|10116.3.peg.15387; -.

Phylogenomic databases

HOVERGEN

P51639; -.

Other

NextBio

607623; -.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Cholesterol biosynthesis; Direct protein sequencing; Endoplasmic reticulum; Glycoprotein; Lipid synthesis; Membrane; NADP; Oxidoreductase; Phosphoprotein; Steroid biosynthesis; Sterol biosynthesis; Transmembrane.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 887`	`887`	`3-hydroxy-3-methylglutaryl-coenzyme A reductase.`	`PRO_0000114424`
`TRANSMEM`	`10 39`	`30`	`Potential.`
`TRANSMEM`	`57 78`	`22`	`Potential.`
`TRANSMEM`	`90 114`	`25`	`Potential.`
`TRANSMEM`	`124 149`	`26`	`Potential.`
`TRANSMEM`	`160 187`	`28`	`Potential.`
`TRANSMEM`	`192 220`	`29`	`Potential.`
`TRANSMEM`	`315 339`	`25`	`Potential.`
`REGION`	`340 449`	`110`	`Linker.`
`REGION`	`450 887`	`438`	`Catalytic.`
`ACT_SITE`	`558 558`		`Charge relay system (By similarity).`
`ACT_SITE`	`690 690`		`Charge relay system (By similarity).`
`ACT_SITE`	`766 766`		`Charge relay system (By similarity).`
`ACT_SITE`	`865 865`		`Proton donor (By similarity).`
`MOD_RES`	`871 871`		`Phosphoserine.`
`CARBOHYD`	`281 281`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`517 517`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`869 869`		`N-linked (GlcNAc...) (Potential).`
`CONFLICT`	`423 423`		`S -> T (in Ref. 4; AA sequence).`
`CONFLICT`	`428 428`		`L -> V (in Ref. 4; AA sequence).`
`CONFLICT`	`443 443`		`P -> N (in Ref. 4; AA sequence).`
`CONFLICT`	`644 653`		`IRLQSKTGDA -> PIRSPKRGTS (in Ref. 3).`
`CONFLICT`	`673 674`		`FF -> GV (in Ref. 1; AAA40608).`
`CONFLICT`	`722 722`		`T -> S (in Ref. 3; CAA39001).`
`CONFLICT`	`750 750`		`A -> L (in Ref. 1; AAA40608).`
`CONFLICT`	`764 764`		`G -> A (in Ref. 3; CAA39001).`

Sequence information

Length: 887 AA [This is the length of the unprocessed precursor]

Molecular weight: 96688 Da [This is the MW of the unprocessed precursor]

CRC64: 856D99A9D5FA965C [This is a checksum on the sequence]

        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 NSTAEQSKVS LGLAEDVSKR 

       310        320        330        340        350        360 
IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QAETESTLSL KNPITSPVVT 

       370        380        390        400        410        420 
PKKAQDNCCR REPLLVRRNQ KLSSVEEDPG VNQDRKVEVI KPLVAEAETS GRATFVLGAS 

       430        440        450        460        470        480 
AASPPLALGA QEPGIELPSE PRPNEECLQI LESAEKGAKF LSDAEIIQLV NAKHIPAYKL 

       490        500        510        520        530        540 
ETLMETHERG VSIRRQLLSA KLAEPSSLQY LPYRDYNYSL VMGACCENVI GYMPIPVGVA 

       550        560        570        580        590        600 
GPLCLDGKEY QVPMATTEGC LVASTNRGCR AISLGGGASS RVLADGMSRG PVVRLPRACD 

       610        620        630        640        650        660 
SAEVKSWLET PEGFAVVKEA FDSTSRFARL QKLHVTLAGR NLYIRLQSKT GDAMGMNMIS 

       670        680        690        700        710        720 
KGTEKALLKL QEFFPELQIL AVSGNYCTDK KPAAINWIEG RGKTVVCEAV IPAKVVREVL 

       730        740        750        760        770        780 
KTTTEAMVDV 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

P51639 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools