Molecule Information

General Information of the Molecule (ID: Mol01878)

• Name: 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) ,Homo sapiens
• Synonyms: HMGCS1; HMGCS
• Molecule Type: Protein
• Gene Name: HMGCS1
• Gene ID: 3157
• Location: chr5:43,287,470-43,313,512[-]
• Sequence:
  MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCT
  DREDINSLCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDI
  EGIDTTNACYGGTAAVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALL
  IGPNAPLIFERGLRGTHMQHAYDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKI
  HAQWQKEGNDKDFTLNDFGFMIFHSPYCKLVQKSLARMLLNDFLNDQNRDKNSIYSGLEA
  FGDVKLEDTYFDRDVEKAFMKASSELFSQKTKASLLVSNQNGNMYTSSVYGSLASVLAQY
  SPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKITASLCDLKSRLDSRTGVAP
  DVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARRPTPNDDTLDEG
  VGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
• 3D-structure: PDB ID: 2P8U; Classification: Transferase; Method: X-ray diffraction; Resolution: 2.00 Å
• Function: Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate, a precursor for cholesterol synthesis.
• Uniprot ID: HMCS1_HUMAN
• Ensembl ID: ENSG00000112972
• HGNC ID: HGNC:5007

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: 7.80E-67; Fold-change: 1.62E-01; Z-score: 2.01E+01
• 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: 7.80E-67; Fold-change: 7.08E-01; Z-score: 1.41E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.43E-16; Fold-change: 6.74E-01; Z-score: 1.66E+00

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