Molecule Information

General Information of the Molecule (ID: Mol01980)

• Name: Dehydrodolichyl diphosphate synthase subunit (DHDDS) ,Homo sapiens
• Synonyms: DHDDS; HDS
• Molecule Type: Protein
• Gene Name: DHDDS
• Gene ID: 79947
• Location: chr1:26,432,282-26,471,306[+]
• Sequence:
  MSWIKEGELSLWERFCANIIKAGPMPKHIAFIMDGNRRYAKKCQVERQEGHSQGFNKLAE
  TLRWCLNLGILEVTVYAFSIENFKRSKSEVDGLMDLARQKFSRLMEEKEKLQKHGVCIRV
  LGDLHLLPLDLQELIAQAVQATKNYNKCFLNVCFAYTSRHEISNAVREMAWGVEQGLLDP
  SDISESLLDKCLYTNRSPHPDILIRTSGEVRLSDFLLWQTSHSCLVFQPVLWPEYTFWNL
  FEAILQFQMNHSVLQKARDMYAEERKRQQLERDQATVTEQLLREGLQASGDAQLRRTRLH
  KLSARREERVQGFLQALELKRADWLARLGTASA
• 3D-structure: PDB ID: 7PAX; Classification: Transferase; Method: X-ray diffraction; Resolution: 2.00 Å
• Function: With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery. Both subunits contribute to enzymatic activity, i.e. condensation of multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol phosphate which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). Synthesizes long-chain polyprenols, mostly of C95 and C100 chain length. Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol.
• Uniprot ID: DHDDS_HUMAN
• Ensembl ID: ENSG00000117682
• HGNC ID: HGNC:20603

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
• 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: 9.28E-26; Fold-change: -4.29E-01; Z-score: -5.30E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.94E-03; Fold-change: -9.11E-02; Z-score: -1.30E-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