Molecule Information

General Information of the Molecule (ID: Mol01877)

• Name: 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) ,Homo sapiens
• Synonyms: HMGCR
• Molecule Type: Protein
• Gene Name: HMGCR
• Gene ID: 3156
• Location: chr5:75,336,329-75,364,001[+]
• Sequence:
  MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS
  DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG
  LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG
  VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR
  VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR
  IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT
  QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS
  SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK
  LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV
  AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC
  DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI
  SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV
  LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL
  MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR
  IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
• 3D-structure: PDB ID: 1DQA; Classification: Oxidoreductase; Method: X-ray diffraction; Resolution: 2.00 Å
• Function: Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis. HMGCR is the main target of statins, a class of cholesterol-lowering drugs.
• Uniprot ID: HMDH_HUMAN
• Ensembl ID: ENSG00000113161
• HGNC ID: HGNC:5006

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Fluvastatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [ICD-11: 2C60.3] [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Fluvastatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.11E-15; Fold-change: 1.01E-01; Z-score: 8.22E+00
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Steroid biosynthesis signaling pathway; Activation; hsa00100
• Cell Pathway Regulation: Terpenoid bacKbone biosynthesis signaling pathway; Activation; hsa00900
• Cell Pathway Regulation: Steroid hormone biosynthesis signaling pathway; Activation; hsa00140
• In Vitro Model: MCF-10A-neoT cells; Breast; Homo sapiens (Human); CVCL_5554
• In Vivo Model: SV40 C3TAg transgenic mouse model; Mus musculus
• Experiment for Molecule Alteration: Clariom D RNA profiling assay
• Experiment for Drug Resistance: MTT assay; Colony formation assay
• Mechanism Description: Acquired resistance to fluvastatin is mediated by restorative upregulation of cholesterol biosynthesis pathway genes.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.11E-15; Fold-change: 6.45E-01; Z-score: 6.03E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.91E-07; Fold-change: 4.57E-01; Z-score: 7.41E-01

References

• Ref 1: Gene signature associated with resistance to fluvastatin chemoprevention for breast cancer .BMC Cancer. 2022 Mar 17;22(1):282. doi: 10.1186/s12885-022-09353-2. 10.1186/s12885-022-09353-2