Reviewed, UniProtKB/Swiss-Prot Q29512 (HMDH_RABIT)

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

Oryctolagus cuniculus (Rabbit)

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	888 AA.
Sequence status	Complete.
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. Peroxisome 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 Peroxisome
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 peroxisome 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 – 888	888	3-hydroxy-3-methylglutaryl-coenzyme A reductase		PRO_0000114423
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 – 888	439	Catalytic
Sites
	Active site	559	1	Charge relay system By similarity
	Active site	691	1	Charge relay system By similarity
	Active site	767	1	Charge relay system By similarity
	Active site	866	1	Proton donor By similarity
Amino acid modifications
	Glycosylation	281	1	N-linked (GlcNAc...) Potential
	Glycosylation	296	1	N-linked (GlcNAc...) Potential
	Glycosylation	518	1	N-linked (GlcNAc...) Potential
	Glycosylation	870	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	Q29512-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 336CDEBF931110D9	FASTA	888	97,300
	10 20 30 40 50 60 MLSRLFRMHG LFVASHPWEV IVGTVTLTIC MMSMNMFTGN DKICGWNYEC 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 NSTADNSKVS LGLDENVSKR 310 320 330 340 350 360 IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QAETESTLSL KNPITSPVVT 370 380 390 400 410 420 QKKVPDSCCR REPVVVRNNQ KFCSVEEEAG MSQDRKVEVI KPLVAETDSP HRAAFVVGGS 430 440 450 460 470 480 SFPDTSLVLE TKEPEIELPK EPRPNEECLQ ILGNAEKGAK FLSDAEIIQL VNAKHIPAYK 490 500 510 520 530 540 LETLMETHER GVSIRRQLLS KKLPEPSSLQ YLPYRDYNYS LVLGACCENV IGYMPIPVGV 550 560 570 580 590 600 VGPLCLDGKE FQVPMATTEG CLVASTNRGC RAICLGGGAS SRVLADGMTR GPVVRLPRAC 610 620 630 640 650 660 DSAEVKAWLE TPEGFAVIKE AFDSTSRFAR LQKLHISMAG RNLYIRFQSR TGDAMGMNMI 670 680 690 700 710 720 SKGTEKALSK LHEYFPEMQI LAVSGNYCTD KKPAAVNWIE GRGKTVVCEA VIPAKVVREV 730 740 750 760 770 780 LKTTTEAMID VNINKNLVGS AMAGSIGGYN AHAANYVTAI YIACGQDAAQ NVGSSNCITL 790 800 810 820 830 840 MEASGPPNED LYISCTMPSI EIGTVGGGTN LLPQQACLQM LGVQGACKDS PGENARQLAR 850 860 870 880 IVCGTVMAGE LSLMAALAAG HLVKSHMIHN RSKINLQDLE GACTKKAA

References

[1]	Yamada M., Yoshimatsu M., Kinowaki M., Kai M., Kondo K., Setoguchi T. Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE. Strain: New Zealand white. Tissue: Liver.

Cross-references

3D structure databases
SMR	Q29512. Positions 441-865.
ModBase	Search...
Protein-protein interaction databases
STRING	Q29512.
Phylogenomic databases
eggNOG	maNOG11482.
HOVERGEN	Q29512.
Enzyme and pathway databases
BRENDA	1.1.1.34. 255.
Family and domain databases
InterPro	IPR002202. HMG_CoA_Rdtase_cat. IPR004554. HMG_CoA_Rdtase_I_cat. IPR004816. HMG_CoA_Rdtase_I_metazoan. IPR009023. HMG_CoA_Rdtase_NAD(P)-bd. IPR009029. HMG_CoA_Rdtase_sub-bd. 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_RABIT

Accession

Primary (citable) accession number: Q29512

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	February 9, 2010
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)