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P04035

- HMDH_HUMAN

UniProt

P04035 - HMDH_HUMAN

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Protein
3-hydroxy-3-methylglutaryl-coenzyme A reductase
Gene
HMGCR
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 activityi

(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH.

Enzyme regulationi

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.1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei559 – 5591Charge relay system
Active sitei691 – 6911Charge relay system
Active sitei767 – 7671Charge relay system
Active sitei866 – 8661Proton donor

GO - Molecular functioni

  1. NADPH binding Source: UniProtKB
  2. coenzyme binding Source: UniProtKB
  3. hydroxymethylglutaryl-CoA reductase (NADPH) activity Source: UniProtKB-EC
  4. hydroxymethylglutaryl-CoA reductase activity Source: UniProtKB
  5. protein binding Source: IntAct

GO - Biological processi

  1. aging Source: Ensembl
  2. cellular lipid metabolic process Source: Reactome
  3. cholesterol biosynthetic process Source: Reactome
  4. coenzyme A metabolic process Source: InterPro
  5. embryo development Source: Ensembl
  6. isoprenoid biosynthetic process Source: Ensembl
  7. myoblast differentiation Source: Ensembl
  8. negative regulation of MAP kinase activity Source: Ensembl
  9. negative regulation of insulin secretion involved in cellular response to glucose stimulus Source: Ensembl
  10. negative regulation of striated muscle cell apoptotic process Source: Ensembl
  11. negative regulation of vasodilation Source: Ensembl
  12. negative regulation of wound healing Source: Ensembl
  13. positive regulation of ERK1 and ERK2 cascade Source: Ensembl
  14. positive regulation of cardiac muscle cell apoptotic process Source: Ensembl
  15. positive regulation of skeletal muscle tissue development Source: Ensembl
  16. positive regulation of smooth muscle cell proliferation Source: Ensembl
  17. positive regulation of stress-activated MAPK cascade Source: Ensembl
  18. protein tetramerization Source: UniProtKB
  19. response to ethanol Source: Ensembl
  20. response to nutrient Source: Ensembl
  21. small molecule metabolic process Source: Reactome
  22. ubiquinone metabolic process Source: Ensembl
  23. visual learning Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS03652-MONOMER.
ReactomeiREACT_116145. PPARA activates gene expression.
REACT_147904. Activation of gene expression by SREBF (SREBP).
REACT_9405. Cholesterol biosynthesis.
SABIO-RKP04035.
UniPathwayiUPA00058; UER00103.

Protein family/group databases

TCDBi2.A.6.6.5. the resistance-nodulation-cell division (rnd) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC:1.1.1.34)
Short name:
HMG-CoA reductase
Gene namesi
Name:HMGCR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:5006. HMGCR.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei10 – 3930Helical; Reviewed prediction
Add
BLAST
Transmembranei57 – 7822Helical; Reviewed prediction
Add
BLAST
Transmembranei90 – 11425Helical; Reviewed prediction
Add
BLAST
Transmembranei124 – 14926Helical; Reviewed prediction
Add
BLAST
Transmembranei160 – 18728Helical; Reviewed prediction
Add
BLAST
Transmembranei192 – 22029Helical; Reviewed prediction
Add
BLAST
Transmembranei315 – 33925Helical; Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB
  2. endoplasmic reticulum membrane Source: UniProtKB
  3. integral component of membrane Source: UniProtKB-KW
  4. peroxisomal membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi75 – 773YIY → AIA: Reduced sterol-mediated release from the ER. Not deglycosylated in response to sterols. 1 Publication
Mutagenesisi89 – 891K → R: Abolishes sterol-mediated ubiquitination and degradation; when associated with R-248. 1 Publication
Mutagenesisi248 – 2481K → R: Abolishes sterol-mediated ubiquitination and degradation; when associated with R-89. 1 Publication

Organism-specific databases

MIMi142910. gene+phenotype.
PharmGKBiPA189.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 8888883-hydroxy-3-methylglutaryl-coenzyme A reductase
PRO_0000114419Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki89 – 89Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki248 – 248Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Glycosylationi281 – 2811N-linked (GlcNAc...) Reviewed prediction
Glycosylationi296 – 2961N-linked (GlcNAc...) Reviewed prediction
Glycosylationi419 – 4191N-linked (GlcNAc...) Reviewed prediction
Glycosylationi518 – 5181N-linked (GlcNAc...) Reviewed prediction
Glycosylationi870 – 8701N-linked (GlcNAc...) Reviewed prediction
Modified residuei872 – 8721Phosphoserine; by AMPK By similarity

Post-translational modificationi

N-glycosylated. Deglycosylated by NGLY1 on release from the endoplasmic reticulum (ER) in a sterol-mediated manner.1 Publication
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.

Keywords - PTMi

Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP04035.
PaxDbiP04035.
PRIDEiP04035.

PTM databases

PhosphoSiteiP04035.

Expressioni

Gene expression databases

ArrayExpressiP04035.
BgeeiP04035.
CleanExiHS_HMGCR.
GenevestigatoriP04035.

Organism-specific databases

HPAiCAB016797.
HPA008338.

Interactioni

Subunit structurei

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 UBIAD1.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
UBIAD1Q9Y5Z93EBI-465513,EBI-2819725
UBIAD1Q9Y5Z9-15EBI-465513,EBI-6621921

Protein-protein interaction databases

BioGridi109399. 10 interactions.
IntActiP04035. 3 interactions.
STRINGi9606.ENSP00000287936.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi445 – 4539
Turni455 – 4573
Helixi458 – 4603
Helixi464 – 4729
Beta strandi474 – 4763
Helixi478 – 4803
Helixi481 – 4844
Beta strandi485 – 4873
Helixi488 – 50215
Beta strandi503 – 5053
Helixi508 – 5114
Beta strandi515 – 5173
Helixi519 – 5213
Turni522 – 5254
Beta strandi528 – 54619
Beta strandi549 – 5568
Helixi562 – 57514
Beta strandi579 – 59012
Beta strandi593 – 5953
Helixi599 – 61012
Helixi612 – 62312
Beta strandi635 – 6395
Beta strandi642 – 6509
Helixi657 – 67418
Beta strandi679 – 6835
Beta strandi686 – 6883
Helixi695 – 7006
Beta strandi703 – 71210
Helixi714 – 7196
Beta strandi721 – 7233
Helixi725 – 73612
Helixi738 – 7425
Beta strandi746 – 7527
Helixi753 – 76311
Helixi768 – 7703
Helixi771 – 7744
Beta strandi777 – 7859
Beta strandi790 – 80011
Beta strandi804 – 8063
Helixi807 – 8104
Helixi812 – 8209
Beta strandi828 – 8303
Helixi833 – 85927
Helixi862 – 8698

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP04035.
SMRiP04035. Positions 441-864.

Miscellaneous databases

EvolutionaryTraceiP04035.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini61 – 218158SSD
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni340 – 449110Linker
Add
BLAST
Regioni450 – 888439Catalytic
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi75 – 784INSIG-binding motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi243 – 2464Poly-Glu

Sequence similaritiesi

Belongs to the HMG-CoA reductase family.

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1257.
HOGENOMiHOG000183489.
HOVERGENiHBG000453.
InParanoidiP04035.
KOiK00021.
OMAiPNEECLQ.
OrthoDBiEOG7GXP9T.
PhylomeDBiP04035.
TreeFamiTF105362.

Family and domain databases

Gene3Di1.10.3270.10. 1 hit.
3.30.70.420. 1 hit.
3.90.770.10. 2 hits.
InterProiIPR002202. 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_dom.
IPR009029. HMG_CoA_Rdtase_sub-bd_dom.
IPR000731. SSD.
[Graphical view]
PANTHERiPTHR10572. PTHR10572. 1 hit.
PfamiPF00368. HMG-CoA_red. 1 hit.
[Graphical view]
PRINTSiPR00071. HMGCOARDTASE.
SUPFAMiSSF55035. SSF55035. 1 hit.
SSF56542. SSF56542. 2 hits.
TIGRFAMsiTIGR00920. 2A060605. 1 hit.
TIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITEiPS00066. 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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P04035-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MLSRLFRMHG LFVASHPWEV IVGTVTLTIC MMSMNMFTGN NKICGWNYEC    50
PKFEEDVLSS DIIILTITRC IAILYIYFQF QNLRQLGSKY ILGIAGLFTI 100
FSSFVFSTVV IHFLDKELTG LNEALPFFLL LIDLSRASTL AKFALSSNSQ 150
DEVRENIARG MAILGPTFTL DALVECLVIG VGTMSGVRQL EIMCCFGCMS 200
VLANYFVFMT FFPACVSLVL ELSRESREGR PIWQLSHFAR VLEEEENKPN 250
PVTQRVKMIM SLGLVLVHAH SRWIADPSPQ NSTADTSKVS LGLDENVSKR 300
IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QTETESTLSL 350
KNPITSPVVT QKKVPDNCCR REPMLVRNNQ KCDSVEEETG INRERKVEVI 400
KPLVAETDTP NRATFVVGNS SLLDTSSVLV TQEPEIELPR EPRPNEECLQ 450
ILGNAEKGAK FLSDAEIIQL VNAKHIPAYK LETLMETHER GVSIRRQLLS 500
KKLSEPSSLQ YLPYRDYNYS LVMGACCENV IGYMPIPVGV AGPLCLDEKE 550
FQVPMATTEG CLVASTNRGC RAIGLGGGAS SRVLADGMTR GPVVRLPRAC 600
DSAEVKAWLE TSEGFAVIKE AFDSTSRFAR LQKLHTSIAG RNLYIRFQSR 650
SGDAMGMNMI SKGTEKALSK LHEYFPEMQI LAVSGNYCTD KKPAAINWIE 700
GRGKSVVCEA VIPAKVVREV LKTTTEAMIE VNINKNLVGS AMAGSIGGYN 750
AHAANIVTAI YIACGQDAAQ NVGSSNCITL MEASGPTNED LYISCTMPSI 800
EIGTVGGGTN LLPQQACLQM LGVQGACKDN PGENARQLAR IVCGTVMAGE 850
LSLMAALAAG HLVKSHMIHN RSKINLQDLQ GACTKKTA 888
Length:888
Mass (Da):97,476
Last modified:November 1, 1986 - v1
Checksum:i49B610DCCCFA26B6
GO
Isoform 2 (identifier: P04035-2) [UniParc]FASTAAdd to Basket

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

Note: No experimental confirmation available.

Show »
Length:835
Mass (Da):92,021
Checksum:i20BBFC6C1FB46ADA
GO
Isoform 3 (identifier: P04035-3) [UniParc]FASTAAdd to Basket

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.

Show »
Length:908
Mass (Da):99,752
Checksum:iA5CAD1217E9C40B9
GO

Sequence cautioni

The sequence BAH12375.1 differs from that shown. Reason: Frameshift at position 122.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti638 – 6381I → V.1 Publication
Corresponds to variant rs5908 [ dbSNP | Ensembl ].
VAR_011954

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MQWMSHTRERDAGSKDSVAT M in isoform 3.
VSP_046492
Alternative sequencei522 – 57453Missing in isoform 2.
VSP_002207Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS4027.1. [P04035-1]
CCDS47234.1. [P04035-2]
PIRiA00356. RDHUE.
RefSeqiNP_000850.1. NM_000859.2. [P04035-1]
NP_001124468.1. NM_001130996.1. [P04035-2]
UniGeneiHs.628096.
Hs.643495.

Genome annotation databases

EnsembliENST00000287936; ENSP00000287936; ENSG00000113161. [P04035-1]
ENST00000343975; ENSP00000340816; ENSG00000113161. [P04035-2]
ENST00000511206; ENSP00000426745; ENSG00000113161. [P04035-1]
GeneIDi3156.
KEGGihsa:3156.
UCSCiuc003kdp.3. human. [P04035-1]
uc003kdq.3. human. [P04035-2]

Polymorphism databases

DMDMi123343.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS4027.1. [P04035-1 ]
CCDS47234.1. [P04035-2 ]
PIRi A00356. RDHUE.
RefSeqi NP_000850.1. NM_000859.2. [P04035-1 ]
NP_001124468.1. NM_001130996.1. [P04035-2 ]
UniGenei Hs.628096.
Hs.643495.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali P04035.
SMRi P04035. Positions 441-864.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109399. 10 interactions.
IntActi P04035. 3 interactions.
STRINGi 9606.ENSP00000287936.

Chemistry

BindingDBi P04035.
ChEMBLi CHEMBL402.
DrugBanki DB01076. Atorvastatin.
DB01393. Bezafibrate.
DB00439. Cerivastatin.
DB01095. Fluvastatin.
DB00227. Lovastatin.
DB00157. NADH.
DB00175. Pravastatin.
DB01098. Rosuvastatin.
DB00641. Simvastatin.
GuidetoPHARMACOLOGYi 639.

Protein family/group databases

TCDBi 2.A.6.6.5. the resistance-nodulation-cell division (rnd) superfamily.

PTM databases

PhosphoSitei P04035.

Polymorphism databases

DMDMi 123343.

Proteomic databases

MaxQBi P04035.
PaxDbi P04035.
PRIDEi P04035.

Protocols and materials databases

DNASUi 3156.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000287936 ; ENSP00000287936 ; ENSG00000113161 . [P04035-1 ]
ENST00000343975 ; ENSP00000340816 ; ENSG00000113161 . [P04035-2 ]
ENST00000511206 ; ENSP00000426745 ; ENSG00000113161 . [P04035-1 ]
GeneIDi 3156.
KEGGi hsa:3156.
UCSCi uc003kdp.3. human. [P04035-1 ]
uc003kdq.3. human. [P04035-2 ]

Organism-specific databases

CTDi 3156.
GeneCardsi GC05P074635.
HGNCi HGNC:5006. HMGCR.
HPAi CAB016797.
HPA008338.
MIMi 142910. gene+phenotype.
neXtProti NX_P04035.
PharmGKBi PA189.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1257.
HOGENOMi HOG000183489.
HOVERGENi HBG000453.
InParanoidi P04035.
KOi K00021.
OMAi PNEECLQ.
OrthoDBi EOG7GXP9T.
PhylomeDBi P04035.
TreeFami TF105362.

Enzyme and pathway databases

UniPathwayi UPA00058 ; UER00103 .
BioCyci MetaCyc:HS03652-MONOMER.
Reactomei REACT_116145. PPARA activates gene expression.
REACT_147904. Activation of gene expression by SREBF (SREBP).
REACT_9405. Cholesterol biosynthesis.
SABIO-RK P04035.

Miscellaneous databases

ChiTaRSi Hmgcr. human.
EvolutionaryTracei P04035.
GeneWikii HMG-CoA_reductase.
GenomeRNAii 3156.
NextBioi 12500.
PROi P04035.
SOURCEi Search...

Gene expression databases

ArrayExpressi P04035.
Bgeei P04035.
CleanExi HS_HMGCR.
Genevestigatori P04035.

Family and domain databases

Gene3Di 1.10.3270.10. 1 hit.
3.30.70.420. 1 hit.
3.90.770.10. 2 hits.
InterProi 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_dom.
IPR009029. HMG_CoA_Rdtase_sub-bd_dom.
IPR000731. SSD.
[Graphical view ]
PANTHERi PTHR10572. PTHR10572. 1 hit.
Pfami PF00368. HMG-CoA_red. 1 hit.
[Graphical view ]
PRINTSi PR00071. HMGCOARDTASE.
SUPFAMi SSF55035. SSF55035. 1 hit.
SSF56542. SSF56542. 2 hits.
TIGRFAMsi TIGR00920. 2A060605. 1 hit.
TIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: VARIANT VAL-638.

Entry informationi

Entry nameiHMDH_HUMAN
AccessioniPrimary (citable) accession number: P04035
Secondary accession number(s): B7Z3Y9, Q8N190
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: September 3, 2014
This is version 175 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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