[1]	NUCLEOTIDE SEQUENCE [MRNA]. PubMed=3841506 [NCBI, ExPASy, EBI, Israel, Japan] Skalnik D.G., Simoni R.D.; "The nucleotide sequence of Syrian hamster HMG-CoA reductase cDNA."; DNA 4:439-444(1985).
[2]	MUTAGENESIS OF HISTIDINE RESIDUES. PubMed=8473286 [NCBI, ExPASy, EBI, Israel, Japan] Darnay B.G., Rodwell V.W.; "His865 is the catalytically important histidyl residue of Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase."; J. Biol. Chem. 268:8429-8435(1993).
[3]	MUTAGENESIS. PubMed=8288583 [NCBI, ExPASy, EBI, Israel, Japan] Frimpong K., Rodwell V.W.; "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."; J. Biol. Chem. 269:1217-1221(1994).

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 .
PATHWAY: Context: Cholesterol biosynthesis .
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

M12705; AAA37077.1; -; mRNA.

[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

A23586; A23586.

3D structure databases

HSSP

P04035; 1HWJ. [HSSP ENTRY / PDB]

SMR

P09610; 461-869.

ModBase

P09610.

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).

BLOCKS

P09610.

Phylogenomic databases

HOVERGEN

P09610; -.

Other

ProtoNet

P09610.

UniRef

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

Keywords

Cholesterol biosynthesis; Endoplasmic reticulum; Glycoprotein; Lipid synthesis; Membrane; NADP; Oxidoreductase; 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_0000114420`
`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).`
`CARBOHYD`	`281 281`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`517 517`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`869 869`		`N-linked (GlcNAc...) (Potential).`
`MUTAGEN`	`474 474`		`H->Q: No loss of activity.`
`MUTAGEN`	`487 487`		`H->Q: No loss of activity.`
`MUTAGEN`	`558 558`		`E->D,Q: Loss of activity.`
`MUTAGEN`	`751 751`		`H->Q: No loss of activity.`
`MUTAGEN`	`766 766`		`D->N: Loss of activity.`
`MUTAGEN`	`860 860`		`H->Q: No loss of activity.`
`MUTAGEN`	`865 865`		`H->K,Q: Loss of activity.`
`MUTAGEN`	`868 868`		`H->Y: No loss of activity.`

Sequence information

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

Molecular weight: 96955 Da [This is the MW of the unprocessed precursor]

CRC64: BC6F9D1F8CAD5EA5 [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 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

P09610 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