Molecule Information

General Information of the Molecule (ID: Mol00638)

• Name: Single-strand selective monofunctional uracil DNA glycosylase (SMUG1) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: SMUG1
• Gene ID: 23583
• Location: chr12:54121277-54189008[-]
• Sequence:
  MPQAFLLGSIHEPAGALMEPQPCPGSLAESFLEEELRLNAELSQLQFSEPVGIIYNPVEY
  AWEPHRNYVTRYCQGPKEVLFLGMNPGPFGMAQTGVPFGEVSMVRDWLGIVGPVLTPPQE
  HPKRPVLGLECPQSEVSGARFWGFFRNLCGQPEVFFHHCFVHNLCPLLFLAPSGRNLTPA
  ELPAKQREQLLGICDAALCRQVQLLGVRLVVGVGRLAEQRARRALAGLMPEVQVEGLLHP
  SPRNPQANKGWEAVAKERLNELGLLPLLLK
• Function: Recognizes base lesions in the genome and initiates base excision DNA repair. Acts as a monofunctional DNA glycosylase specific for uracil (U) residues in DNA with a preference for single-stranded DNA substrates. The activity is greater toward mismatches (U/G) compared to matches (U/A). Excises uracil (U), 5-formyluracil (fU) and uracil derivatives bearing an oxidized group at C5 [5-hydroxyuracil (hoU) and 5-hydroxymethyluracil (hmU)] in ssDNA and dsDNA, but not analogous cytosine derivatives (5-hydroxycytosine and 5-formylcytosine), nor other oxidized bases. The activity is damage-specific and salt-dependent. The substrate preference is the following: ssDNA > dsDNA (G pair) = dsDNA (A pair) at low salt concentration, and dsDNA (G pair) > dsDNA (A pair) > ssDNA at high salt concentration.
• Uniprot ID: SMUG1_HUMAN
• Ensembl ID: ENSG00000123415
• HGNC ID: HGNC:17148

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

Fluorouracil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric adenocarcinoma [1]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: MkN-45-miR-31 showed an increased sensitivity to 5-FU, decreased migration and cell invasion compared to the control groups and induction of miR-31 expression in MkN-45 caused a significant reduction of E2F6 and SMUG1 genes.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.70E-01; Fold-change: 4.37E-01; Z-score: 5.97E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 8.34E-05; Fold-change: 4.78E-01; Z-score: 1.11E+00

References

• Ref 1: Induction of miR-31 causes increased sensitivity to 5-FU and decreased migration and cell invasion in gastric adenocarcinoma. Bratisl Lek Listy. 2019;120(1):35-39. doi: 10.4149/BLL_2019_005.