P04035 (HMDH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	888 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
Catalytic activity	(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH.
Enzyme regulation	Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate. Inhibited by statins, a class of hypolipidemic agents used as pharmaceuticals to lower cholesterol levels in individuals at risk from cardiovascular disease due to hypercholesterolemia. Inhibition of HMGCR in the liver stimulates the LDL-receptors, which results in an increased clearance of LDL from the bloodstream and a decrease in blood cholesterol levels. The first results can be seen after one week of statin use and the effect is maximal after four to six weeks. Ref.7
Pathway	Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
Subunit structure	Homodimer. Interacts (via its SSD) with INSIG1; the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Ref.8 Ref.9 Ref.12
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein.
Post-translational modification	N-glycosylated. Deglycosylated by NGLY1 on release from the endoplasmic reticulum (ER) in a sterol-mediated manner. Ref.9 Undergoes sterol-mediated ubiquitination and ER-association degradation (ERAD). Accumulation of sterols in the endoplasmic reticulum (ER) membrane, triggers binding of the reductase to the ER membrane protein INSIG1. This INSIG1 binding leads to the recruitment of the ubiquitin ligase, AMFR/gp78, initiating ubiquitination of the reductase. The ubiquitinated reductase is then extracted from the ER membrane and delivered to cytosolic 26S proteosomes by a mechanism probably mediated by the ATPase Valosin-containing protein VCP/p97. Lys-248 is the main site of ubiquitination. Ubiquitination is enhanced by the presence of a geranylgeranylated protein.
Sequence similarities	Belongs to the HMG-CoA reductase family. Contains 1 SSD (sterol-sensing) domain.
Sequence caution	The sequence BAH12375.1 differs from that shown. Reason: Frameshift at position 122.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Cholesterol metabolism Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara cellular lipid metabolic process Traceable author statement. Source: Reactome cholesterol biosynthetic process Traceable author statement. Source: Reactome coenzyme A metabolic process Inferred from electronic annotation. Source: InterPro embryo development Inferred from electronic annotation. Source: Compara isoprenoid biosynthetic process Inferred from electronic annotation. Source: Compara myoblast differentiation Inferred from electronic annotation. Source: Compara negative regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara negative regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara negative regulation of striated muscle cell apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of vasodilation Inferred from electronic annotation. Source: Compara negative regulation of wound healing Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of cardiac muscle cell apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of skeletal muscle tissue development Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of stress-activated MAPK cascade Inferred from electronic annotation. Source: Compara protein tetramerization Inferred from direct assay Ref.12. Source: UniProtKB response to ethanol Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara ubiquinone metabolic process Inferred from electronic annotation. Source: Compara visual learning Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum membrane Traceable author statement Ref.1. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW peroxisomal membrane Inferred from direct assay PubMed 17180682. Source: UniProtKB
Molecular_function	NADPH binding Inferred from direct assay Ref.12. Source: UniProtKB hydroxymethylglutaryl-CoA reductase (NADPH) activity Inferred from electronic annotation. Source: EC hydroxymethylglutaryl-CoA reductase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P04035-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P04035-2)

The sequence of this isoform differs from the canonical sequence as follows:
     522-574: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: P04035-3)

Also known as: HMGCR-1b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQWMSHTRERDAGSKDSVATM

Note: Most highly expressed transcript in skin, esophagus, and uterine cervix.

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_0000114419

Regions

Transmembrane

10 – 39

30

Helical; Potential

Transmembrane

57 – 78

22

Helical; Potential

Transmembrane

90 – 114

25

Helical; Potential

Transmembrane

124 – 149

26

Helical; Potential

Transmembrane

160 – 187

28

Helical; Potential

Transmembrane

192 – 220

29

Helical; Potential

Transmembrane

315 – 339

25

Helical; Potential

Domain

61 – 218

158

SSD

Region

340 – 449

110

Linker

Region

450 – 888

439

Catalytic

Motif

75 – 78

4

INSIG-binding motif

Compositional bias

243 – 246

4

Poly-Glu

Sites

Active site

559

1

Charge relay system

Active site

691

1

Charge relay system

Active site

767

1

Charge relay system

Active site

866

1

Proton donor

Amino acid modifications

Modified residue

872

1

Phosphoserine; by AMPK By similarity

Glycosylation

281

1

N-linked (GlcNAc...) Potential

Glycosylation

296

1

N-linked (GlcNAc...) Potential

Glycosylation

419

1

N-linked (GlcNAc...) Potential

Glycosylation

518

1

N-linked (GlcNAc...) Potential

Glycosylation

870

1

N-linked (GlcNAc...) Potential

Cross-link

89

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9

Cross-link

248

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9

Natural variations

Alternative sequence

1

1

M → MQWMSHTRERDAGSKDSVAT M in isoform 3.

VSP_046492

Alternative sequence

522 – 574

53

Missing in isoform 2.

VSP_002207

Natural variant

638

1

I → V. Ref.15
Corresponds to variant rs5908 [ dbSNP | Ensembl ].

VAR_011954

Experimental info

Mutagenesis

75 – 77

3

YIY → AIA: Reduced sterol-mediated release from the ER. Not deglycosylated in response to sterols. Ref.9

Mutagenesis

89

1

K → R: Abolishes sterol-mediated ubiquitination and degradation; when associated with R-248. Ref.9

Mutagenesis

248

1

K → R: Abolishes sterol-mediated ubiquitination and degradation; when associated with R-89. Ref.9

Secondary structure

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888

Helix Strand Turn

Details...

Helix

445 – 453

9

Turn

455 – 457

3

Helix

458 – 460

3

Helix

464 – 472

9

Beta strand

474 – 476

3

Helix

478 – 480

3

Helix

481 – 484

4

Beta strand

485 – 487

3

Helix

488 – 502

15

Beta strand

503 – 505

3

Helix

508 – 511

4

Beta strand

515 – 517

3

Helix

519 – 521

3

Turn

522 – 525

4

Beta strand

528 – 546

19

Beta strand

549 – 556

8

Helix

562 – 575

14

Beta strand

579 – 590

12

Beta strand

593 – 595

3

Helix

599 – 610

12

Helix

612 – 623

12

Beta strand

635 – 639

5

Beta strand

642 – 650

9

Helix

657 – 674

18

Beta strand

679 – 683

5

Beta strand

686 – 688

3

Helix

695 – 700

6

Beta strand

703 – 712

10

Helix

714 – 719

6

Beta strand

721 – 723

3

Helix

725 – 736

12

Helix

738 – 742

5

Beta strand

746 – 752

7

Helix

753 – 763

11

Helix

768 – 770

3

Helix

771 – 774

4

Beta strand

777 – 785

9

Beta strand

790 – 800

11

Beta strand

804 – 806

3

Helix

807 – 810

4

Helix

812 – 820

9

Beta strand

828 – 830

3

Helix

833 – 859

27

Helix

862 – 869

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1986. Version 1. Checksum: 49B610DCCCFA26B6	FASTA	888	97,476
	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 LIDLSRASTL 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 NSTADTSKVS LGLDENVSKR 310 320 330 340 350 360 IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QTETESTLSL KNPITSPVVT 370 380 390 400 410 420 QKKVPDNCCR REPMLVRNNQ KCDSVEEETG INRERKVEVI KPLVAETDTP NRATFVVGNS 430 440 450 460 470 480 SLLDTSSVLV TQEPEIELPR EPRPNEECLQ ILGNAEKGAK FLSDAEIIQL VNAKHIPAYK 490 500 510 520 530 540 LETLMETHER GVSIRRQLLS KKLSEPSSLQ YLPYRDYNYS LVMGACCENV IGYMPIPVGV 550 560 570 580 590 600 AGPLCLDEKE FQVPMATTEG CLVASTNRGC RAIGLGGGAS SRVLADGMTR GPVVRLPRAC 610 620 630 640 650 660 DSAEVKAWLE TSEGFAVIKE AFDSTSRFAR LQKLHTSIAG RNLYIRFQSR SGDAMGMNMI 670 680 690 700 710 720 SKGTEKALSK LHEYFPEMQI LAVSGNYCTD KKPAAINWIE GRGKSVVCEA VIPAKVVREV 730 740 750 760 770 780 LKTTTEAMIE VNINKNLVGS AMAGSIGGYN AHAANIVTAI YIACGQDAAQ NVGSSNCITL 790 800 810 820 830 840 MEASGPTNED LYISCTMPSI EIGTVGGGTN LLPQQACLQM LGVQGACKDN PGENARQLAR 850 860 870 880 IVCGTVMAGE LSLMAALAAG HLVKSHMIHN RSKINLQDLQ GACTKKTA
	Isoform 2 [UniParc]. Checksum: 20BBFC6C1FB46ADA	FASTA	835	92,021
	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 LIDLSRASTL 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 NSTADTSKVS LGLDENVSKR 310 320 330 340 350 360 IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QTETESTLSL KNPITSPVVT 370 380 390 400 410 420 QKKVPDNCCR REPMLVRNNQ KCDSVEEETG INRERKVEVI KPLVAETDTP NRATFVVGNS 430 440 450 460 470 480 SLLDTSSVLV TQEPEIELPR EPRPNEECLQ ILGNAEKGAK FLSDAEIIQL VNAKHIPAYK 490 500 510 520 530 540 LETLMETHER GVSIRRQLLS KKLSEPSSLQ YLPYRDYNYS LLGGGASSRV LADGMTRGPV 550 560 570 580 590 600 VRLPRACDSA EVKAWLETSE GFAVIKEAFD STSRFARLQK LHTSIAGRNL YIRFQSRSGD 610 620 630 640 650 660 AMGMNMISKG TEKALSKLHE YFPEMQILAV SGNYCTDKKP AAINWIEGRG KSVVCEAVIP 670 680 690 700 710 720 AKVVREVLKT TTEAMIEVNI NKNLVGSAMA GSIGGYNAHA ANIVTAIYIA CGQDAAQNVG 730 740 750 760 770 780 SSNCITLMEA SGPTNEDLYI SCTMPSIEIG TVGGGTNLLP QQACLQMLGV QGACKDNPGE 790 800 810 820 830 NARQLARIVC GTVMAGELSL MAALAAGHLV KSHMIHNRSK INLQDLQGAC TKKTA
	Isoform 3 (HMGCR-1b) [UniParc]. Checksum: A5CAD1217E9C40B9	FASTA	908	99,752
	10 20 30 40 50 60 MQWMSHTRER DAGSKDSVAT MLSRLFRMHG LFVASHPWEV IVGTVTLTIC MMSMNMFTGN 70 80 90 100 110 120 NKICGWNYEC PKFEEDVLSS DIIILTITRC IAILYIYFQF QNLRQLGSKY ILGIAGLFTI 130 140 150 160 170 180 FSSFVFSTVV IHFLDKELTG LNEALPFFLL LIDLSRASTL AKFALSSNSQ DEVRENIARG 190 200 210 220 230 240 MAILGPTFTL DALVECLVIG VGTMSGVRQL EIMCCFGCMS VLANYFVFMT FFPACVSLVL 250 260 270 280 290 300 ELSRESREGR PIWQLSHFAR VLEEEENKPN PVTQRVKMIM SLGLVLVHAH SRWIADPSPQ 310 320 330 340 350 360 NSTADTSKVS LGLDENVSKR IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE 370 380 390 400 410 420 QTETESTLSL KNPITSPVVT QKKVPDNCCR REPMLVRNNQ KCDSVEEETG INRERKVEVI 430 440 450 460 470 480 KPLVAETDTP NRATFVVGNS SLLDTSSVLV TQEPEIELPR EPRPNEECLQ ILGNAEKGAK 490 500 510 520 530 540 FLSDAEIIQL VNAKHIPAYK LETLMETHER GVSIRRQLLS KKLSEPSSLQ YLPYRDYNYS 550 560 570 580 590 600 LVMGACCENV IGYMPIPVGV AGPLCLDEKE FQVPMATTEG CLVASTNRGC RAIGLGGGAS 610 620 630 640 650 660 SRVLADGMTR GPVVRLPRAC DSAEVKAWLE TSEGFAVIKE AFDSTSRFAR LQKLHTSIAG 670 680 690 700 710 720 RNLYIRFQSR SGDAMGMNMI SKGTEKALSK LHEYFPEMQI LAVSGNYCTD KKPAAINWIE 730 740 750 760 770 780 GRGKSVVCEA VIPAKVVREV LKTTTEAMIE VNINKNLVGS AMAGSIGGYN AHAANIVTAI 790 800 810 820 830 840 YIACGQDAAQ NVGSSNCITL MEASGPTNED LYISCTMPSI EIGTVGGGTN LLPQQACLQM 850 860 870 880 890 900 LGVQGACKDN PGENARQLAR IVCGTVMAGE LSLMAALAAG HLVKSHMIHN RSKINLQDLQ GACTKKTA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation." Luskey K.L., Stevens B. J. Biol. Chem. 260:10271-10277(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Human HMG-CoA reductase gene." Nakajima T., Iwaki K., Hamakubo T., Kodama T., Emi M. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D., Toth E.J., Nickerson D.A. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Thalamus.
[5]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Blood.
[7]	"Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth." Brown M.S., Goldstein J.L. J. Lipid Res. 21:505-517(1980) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[8]	"Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain." Sever N., Yang T., Brown M.S., Goldstein J.L., DeBose-Boyd R.A. Mol. Cell 11:25-33(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INSIG1, UBIQUITINATION.
[9]	"Dislocation of HMG-CoA reductase and Insig-1, two polytopic endoplasmic reticulum proteins, en route to proteasomal degradation." Leichner G.S., Avner R., Harats D., Roitelman J. Mol. Biol. Cell 20:3330-3341(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INSIG1, UBIQUITINATION AT LYS-89 AND LYS-248, GLYCOSYLATION, MUTAGENESIS OF 75-TYR--TYR-77; LYS-89 AND LYS-248.
[10]	"Metabolically regulated endoplasmic reticulum-associated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase: evidence for requirement of a geranylgeranylated protein." Leichner G.S., Avner R., Harats D., Roitelman J. J. Biol. Chem. 286:32150-32161(2011) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[11]	"A novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) splice variant with an alternative exon 1 potentially encoding an extended N-terminus." Stormo C., Kringen M.K., Grimholt R.M., Berg J.P., Piehler A.P. BMC Mol. Biol. 13:29-29(2012) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY (ISOFORM 3), ALTERNATIVE SPLICING.
[12]	"Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis." Istvan E.S., Palnitkar M., Buchanan S.K., Deisenhofer J. EMBO J. 19:819-830(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 422-888, SUBUNIT.
[13]	"Structural mechanism for statin inhibition of HMG-CoA reductase." Istvan E.S., Deisenhofer J. Science 292:1160-1164(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 426-888.
[14]	"Thermodynamic and structure guided design of statin based inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase." Sarver R.W., Bills E., Bolton G., Bratton L.D., Caspers N.L., Dunbar J.B., Harris M.S., Hutchings R.H., Kennedy R.M., Larsen S.D., Pavlovsky A., Pfefferkorn J.A., Bainbridge G. J. Med. Chem. 51:3804-3813(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 441-875 IN COMPLEX WITH STATIN-BASED INHIBITORS.
[15]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VAL-638.
[16]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M11058 mRNA. Translation: AAA52679.1.
AF273765 , AF273754, AF273755, AF273756, AF273757, AF273758, AF273759, AF273760, AF273761, AF273762, AF273763, AF273764 Genomic DNA. Translation: AAG21343.1.
AY321356 Genomic DNA. Translation: AAP72015.1.
AK296499 mRNA. Translation: BAH12375.1. Frameshift.
AC008897 Genomic DNA. No translation available.
BC033692 mRNA. Translation: AAH33692.1.

IPI

IPI00021770.
IPI00221382.
IPI00922451.

PIR

RDHUE. A00356.

RefSeq

NP_000850.1. NM_000859.2.
NP_001124468.1. NM_001130996.1.

UniGene

Hs.628096.
Hs.643495.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DQ8	X-ray	2.10	A/B/C/D	426-888	[»]
1DQ9	X-ray	2.80	A/B/C/D	426-888	[»]
1DQA	X-ray	2.00	A/B/C/D	426-888	[»]
1HW8	X-ray	2.10	A/B/C/D	426-888	[»]
1HW9	X-ray	2.33	A/B/C/D	426-888	[»]
1HWI	X-ray	2.30	A/B/C/D	426-888	[»]
1HWJ	X-ray	2.26	A/B/C/D	426-888	[»]
1HWK	X-ray	2.22	A/B/C/D	426-888	[»]
1HWL	X-ray	2.10	A/B/C/D	426-888	[»]
2Q1L	X-ray	2.05	A/B/C/D	441-875	[»]
2Q6B	X-ray	2.00	A/B/C/D	441-875	[»]
2Q6C	X-ray	2.00	A/B/C/D	441-875	[»]
2R4F	X-ray	1.70	A/B/C/D	441-875	[»]
3BGL	X-ray	2.23	A/B/C/D	441-875	[»]
3CCT	X-ray	2.12	A/B/C/D	441-875	[»]
3CCW	X-ray	2.10	A/B/C/D	441-875	[»]
3CCZ	X-ray	1.70	A/B/C/D	441-875	[»]
3CD0	X-ray	2.40	A/B/C/D	441-875	[»]
3CD5	X-ray	2.39	A/B/C/D	441-875	[»]
3CD7	X-ray	2.05	A/B/C/D	441-875	[»]
3CDA	X-ray	2.07	A/B/C/D	441-875	[»]
3CDB	X-ray	2.30	A/B/C/D	441-875	[»]

ProteinModelPortal

P04035.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04035. 1 interaction.

STRING

9606.ENSP00000287936.

Protein family/group databases

TCDB

2.A.6.6.5. resistance-nodulation-cell division (RND) superfamily.

PTM databases

PhosphoSite

P04035.

Polymorphism databases

DMDM

123343.

Proteomic databases

PaxDb

P04035.

PRIDE

P04035.

Protocols and materials databases

DNASU

3156.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000287936; ENSP00000287936; ENSG00000113161.
ENST00000343975; ENSP00000340816; ENSG00000113161.
ENST00000511206; ENSP00000426745; ENSG00000113161.

GeneID

3156.

KEGG

hsa:3156.

UCSC

uc003kdp.3. human.
uc003kdq.3. human.

Organism-specific databases

CTD

3156.

GeneCards

GC05P074635.

HGNC

HGNC:5006. HMGCR.

HPA

CAB016797.
HPA008338.

MIM

142910. gene+phenotype.

neXtProt

NX_P04035.

PharmGKB

PA189.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1257.

HOGENOM

HOG000183489.

HOVERGEN

HBG000453.

InParanoid

P04035.

KO

K00021.

OMA

SPVVTQK.

PhylomeDB

P04035.

Enzyme and pathway databases

BioCyc

MetaCyc:HS03652-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P04035.

UniPathway

UPA00058; UER00103.

Gene expression databases

ArrayExpress

P04035.

Bgee

P04035.

CleanEx

HS_HMGCR.

Genevestigator

P04035.

GermOnline

ENSG00000113161. Homo sapiens.

Family and domain databases

Gene3D

1.10.3270.10. 1 hit.
3.30.70.420. 1 hit.
3.90.770.10. 2 hits.

InterPro

IPR002202. HMG_CoA_Rdtase.
IPR023074. HMG_CoA_Rdtase_cat.
IPR023076. HMG_CoA_Rdtase_CS.
IPR004554. HMG_CoA_Rdtase_eu_arc.
IPR004816. HMG_CoA_Rdtase_metazoan.
IPR023282. HMG_CoA_Rdtase_N.
IPR009023. HMG_CoA_Rdtase_NAD(P)-bd.
IPR009029. HMG_CoA_Rdtase_sub-bd.
IPR000731. SSD.
[Graphical view]

PANTHER

PTHR10572. PTHR10572. 1 hit.

Pfam

PF00368. HMG-CoA_red. 1 hit.
[Graphical view]

PRINTS

PR00071. HMGCOARDTASE.

SUPFAM

SSF55035. HMG_CoA_NAD_bind. 1 hit.
SSF56542. HMG_CoA_sub_bind. 1 hit.

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...

Other

BindingDB

P04035.

ChEMBL

CHEMBL402.

ChiTaRS

Hmgcr. human.

DrugBank

DB01076. Atorvastatin.
DB01393. Bezafibrate.
DB00439. Cerivastatin.
DB01095. Fluvastatin.
DB00227. Lovastatin.
DB00157. NADH.
DB00175. Pravastatin.
DB01098. Rosuvastatin.
DB00641. Simvastatin.

EvolutionaryTrace

P04035.

GenomeRNAi

3156.

NextBio

12500.

SOURCE

Search...

Entry information

Entry name

HMDH_HUMAN

Accession

Primary (citable) accession number: P04035
Secondary accession number(s): B7Z3Y9, Q8N190

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	November 1, 1986
Last modified:	May 1, 2013
This is version 161 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.