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P04035 (HMDH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 174. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
3-hydroxy-3-methylglutaryl-coenzyme A reductase

Short name=HMG-CoA reductase
EC=1.1.1.34
Gene names
Name:HMGCR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length888 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Interacts with UBIAD1. Ref.8 Ref.9 Ref.12 Ref.13

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 processCholesterol biosynthesis
Cholesterol metabolism
Lipid biosynthesis
Lipid metabolism
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandNADP
   Molecular functionOxidoreductase
   PTMGlycoprotein
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

isoprenoid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

myoblast differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of MAP kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of striated muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of vasodilation

Inferred from electronic annotation. Source: Ensembl

negative regulation of wound healing

Inferred from electronic annotation. Source: Ensembl

positive regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of cardiac muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of skeletal muscle tissue development

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of stress-activated MAPK cascade

Inferred from electronic annotation. Source: Ensembl

protein tetramerization

Inferred from direct assay Ref.13. Source: UniProtKB

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

ubiquinone metabolic process

Inferred from electronic annotation. Source: Ensembl

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendoplasmic reticulum

Inferred from direct assay PubMed 17180682. Source: UniProtKB

endoplasmic reticulum membrane

Traceable author statement Ref.1. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

peroxisomal membrane

Inferred from direct assay PubMed 17180682. Source: UniProtKB

   Molecular_functionNADPH binding

Inferred from direct assay Ref.13. Source: UniProtKB

coenzyme binding

Inferred from direct assay Ref.13. Source: UniProtKB

hydroxymethylglutaryl-CoA reductase (NADPH) activity

Inferred from electronic annotation. Source: UniProtKB-EC

hydroxymethylglutaryl-CoA reductase activity

Inferred from direct assay Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.12. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

UBIAD1Q9Y5Z93EBI-465513,EBI-2819725
UBIAD1Q9Y5Z9-15EBI-465513,EBI-6621921

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 8888883-hydroxy-3-methylglutaryl-coenzyme A reductase
PRO_0000114419

Regions

Transmembrane10 – 3930Helical; Potential
Transmembrane57 – 7822Helical; Potential
Transmembrane90 – 11425Helical; Potential
Transmembrane124 – 14926Helical; Potential
Transmembrane160 – 18728Helical; Potential
Transmembrane192 – 22029Helical; Potential
Transmembrane315 – 33925Helical; Potential
Domain61 – 218158SSD
Region340 – 449110Linker
Region450 – 888439Catalytic
Motif75 – 784INSIG-binding motif
Compositional bias243 – 2464Poly-Glu

Sites

Active site5591Charge relay system
Active site6911Charge relay system
Active site7671Charge relay system
Active site8661Proton donor

Amino acid modifications

Modified residue8721Phosphoserine; by AMPK By similarity
Glycosylation2811N-linked (GlcNAc...) Potential
Glycosylation2961N-linked (GlcNAc...) Potential
Glycosylation4191N-linked (GlcNAc...) Potential
Glycosylation5181N-linked (GlcNAc...) Potential
Glycosylation8701N-linked (GlcNAc...) Potential
Cross-link89Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Cross-link248Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9

Natural variations

Alternative sequence11M → MQWMSHTRERDAGSKDSVAT M in isoform 3.
VSP_046492
Alternative sequence522 – 57453Missing in isoform 2.
VSP_002207
Natural variant6381I → V. Ref.16
Corresponds to variant rs5908 [ dbSNP | Ensembl ].
VAR_011954

Experimental info

Mutagenesis75 – 773YIY → AIA: Reduced sterol-mediated release from the ER. Not deglycosylated in response to sterols. Ref.9
Mutagenesis891K → R: Abolishes sterol-mediated ubiquitination and degradation; when associated with R-248. Ref.9
Mutagenesis2481K → R: Abolishes sterol-mediated ubiquitination and degradation; when associated with R-89. Ref.9

Secondary structure

................................................................................ 888
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1986. Version 1.
Checksum: 49B610DCCCFA26B6

FASTA88897,476
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 20BBFC6C1FB46ADA
Show »

FASTA83592,021
Isoform 3 (HMGCR-1b) [UniParc].

Checksum: A5CAD1217E9C40B9
Show »

FASTA90899,752

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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]"The UBIAD1 prenyltransferase links menaquione-4 synthesis to cholesterol metabolic enzymes."
Nickerson M.L., Bosley A.D., Weiss J.S., Kostiha B.N., Hirota Y., Brandt W., Esposito D., Kinoshita S., Wessjohann L., Morham S.G., Andresson T., Kruth H.S., Okano T., Dean M.
Hum. Mutat. 34:317-329(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBIAD1.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
[17]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 expand/collapse EMBL AC list , 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.
CCDSCCDS4027.1. [P04035-1]
CCDS47234.1. [P04035-2]
PIRRDHUE. A00356.
RefSeqNP_000850.1. NM_000859.2. [P04035-1]
NP_001124468.1. NM_001130996.1. [P04035-2]
UniGeneHs.628096.
Hs.643495.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DQ8X-ray2.10A/B/C/D426-888[»]
1DQ9X-ray2.80A/B/C/D426-888[»]
1DQAX-ray2.00A/B/C/D426-888[»]
1HW8X-ray2.10A/B/C/D426-888[»]
1HW9X-ray2.33A/B/C/D426-888[»]
1HWIX-ray2.30A/B/C/D426-888[»]
1HWJX-ray2.26A/B/C/D426-888[»]
1HWKX-ray2.22A/B/C/D426-888[»]
1HWLX-ray2.10A/B/C/D426-888[»]
2Q1LX-ray2.05A/B/C/D441-875[»]
2Q6BX-ray2.00A/B/C/D441-875[»]
2Q6CX-ray2.00A/B/C/D441-875[»]
2R4FX-ray1.70A/B/C/D441-875[»]
3BGLX-ray2.23A/B/C/D441-875[»]
3CCTX-ray2.12A/B/C/D441-875[»]
3CCWX-ray2.10A/B/C/D441-875[»]
3CCZX-ray1.70A/B/C/D441-875[»]
3CD0X-ray2.40A/B/C/D441-875[»]
3CD5X-ray2.39A/B/C/D441-875[»]
3CD7X-ray2.05A/B/C/D441-875[»]
3CDAX-ray2.07A/B/C/D441-875[»]
3CDBX-ray2.30A/B/C/D441-875[»]
ProteinModelPortalP04035.
SMRP04035. Positions 441-864.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109399. 10 interactions.
IntActP04035. 3 interactions.
STRING9606.ENSP00000287936.

Chemistry

BindingDBP04035.
ChEMBLCHEMBL402.
DrugBankDB01076. Atorvastatin.
DB01393. Bezafibrate.
DB00439. Cerivastatin.
DB01095. Fluvastatin.
DB00227. Lovastatin.
DB00157. NADH.
DB00175. Pravastatin.
DB01098. Rosuvastatin.
DB00641. Simvastatin.
GuidetoPHARMACOLOGY639.

Protein family/group databases

TCDB2.A.6.6.5. the resistance-nodulation-cell division (rnd) superfamily.

PTM databases

PhosphoSiteP04035.

Polymorphism databases

DMDM123343.

Proteomic databases

MaxQBP04035.
PaxDbP04035.
PRIDEP04035.

Protocols and materials databases

DNASU3156.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287936; ENSP00000287936; ENSG00000113161. [P04035-1]
ENST00000343975; ENSP00000340816; ENSG00000113161. [P04035-2]
ENST00000511206; ENSP00000426745; ENSG00000113161. [P04035-1]
GeneID3156.
KEGGhsa:3156.
UCSCuc003kdp.3. human. [P04035-1]
uc003kdq.3. human. [P04035-2]

Organism-specific databases

CTD3156.
GeneCardsGC05P074635.
HGNCHGNC:5006. HMGCR.
HPACAB016797.
HPA008338.
MIM142910. gene+phenotype.
neXtProtNX_P04035.
PharmGKBPA189.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1257.
HOGENOMHOG000183489.
HOVERGENHBG000453.
InParanoidP04035.
KOK00021.
OMAPNEECLQ.
OrthoDBEOG7GXP9T.
PhylomeDBP04035.
TreeFamTF105362.

Enzyme and pathway databases

BioCycMetaCyc:HS03652-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP04035.
UniPathwayUPA00058; UER00103.

Gene expression databases

ArrayExpressP04035.
BgeeP04035.
CleanExHS_HMGCR.
GenevestigatorP04035.

Family and domain databases

Gene3D1.10.3270.10. 1 hit.
3.30.70.420. 1 hit.
3.90.770.10. 2 hits.
InterProIPR002202. 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]
PANTHERPTHR10572. PTHR10572. 1 hit.
PfamPF00368. HMG-CoA_red. 1 hit.
[Graphical view]
PRINTSPR00071. HMGCOARDTASE.
SUPFAMSSF55035. SSF55035. 1 hit.
SSF56542. SSF56542. 2 hits.
TIGRFAMsTIGR00920. 2A060605. 1 hit.
TIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITEPS00066. 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]
ProtoNetSearch...

Other

ChiTaRSHmgcr. human.
EvolutionaryTraceP04035.
GeneWikiHMG-CoA_reductase.
GenomeRNAi3156.
NextBio12500.
PROP04035.
SOURCESearch...

Entry information

Entry nameHMDH_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 174 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM