Molecule Information

General Information of the Molecule (ID: Mol00238)

• Name: Ubiquitin-like-conjugating enzyme ATG3 (ATG3) ,Homo sapiens
• Synonyms: Autophagy-related protein 3; APG3-like; hApg3; Protein PC3-96; APG3; APG3L
• Molecule Type: Protein
• Gene Name: ATG3
• Gene ID: 64422
• Location: chr3:112532510-112562046[-]
• Sequence:
  MQNVINTVKGKALEVAEYLTPVLKESKFKETGVITPEEFVAAGDHLVHHCPTWQWATGEE
  LKVKAYLPTGKQFLVTKNVPCYKRCKQMEYSDELEAIIEEDDGDGGWVDTYHNTGITGIT
  EAVKEITLENKDNIRLQDCSALCEEEEDEDEGEAADMEEYEESGLLETDEATLDTRKIVE
  ACKAKTDAGGEDAILQTRTYDLYITYDKYYQTPRLWLFGYDEQRQPLTVEHMYEDISQDH
  VKKTVTIENHPHLPPPPMCSVHPCRHAEVMKKIIETVAEGGGELGVHMYLLIFLKFVQAV
  IPTIEYDYTRHFTM
• Function: E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes the transfer of ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE). This step is required for the membrane association of ATG8-like proteins. The formation of the ATG8-phosphatidylethanolamine conjugates is essential for autophagy and for the cytoplasm to vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing the conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing a role in mitochondrial homeostasis but not in autophagy. ATG7 (E1-like enzyme) facilitates this reaction by forming an E1-E2 complex with ATG3. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway.
• Uniprot ID: ATG3_HUMAN
• Ensembl ID: ENSG00000144848
• HGNC ID: HGNC:20962

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

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Oral squamous cell carcinoma [1]

• Sensitive Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Sensitive Drug: Cisplatin
• 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 autophagy; Inhibition; hsa04140
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: CAL-27 cells; Tongue; Homo sapiens (Human); CVCL_1107
• In Vitro Model: KB cells; Gastric; Homo sapiens (Human); CVCL_0372
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: After HOTAIR silence, autophagy was inhibited with the downregulated expression of MAP1LC3B (microtubule-associated protein 1 light chain 3B), beclin1, and autophagy-related gene (ATG) 3 and ATG7. The expressions of mTOR increased, which promoted the sensitivity to cisplatin.

Disease Class: Non-small cell lung cancer [2]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR-1 enhanced DDP sensitivity of DDP resistant NSCLC cells by downregulating ATG3.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Oral squamous cell carcinoma [ICD-11: 2B6E]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Oral tissue
• The Specified Disease: Oral squamous cell carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.28E-04; Fold-change: 4.96E-01; Z-score: 1.03E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 9.08E-01; Fold-change: -1.12E-02; Z-score: -3.15E-02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.89E-01; Fold-change: -2.42E-02; Z-score: -9.99E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.07E-13; Fold-change: 1.73E-01; Z-score: 8.04E-01

References

• Ref 1: RNA interference of long noncoding RNA HOTAIR suppresses autophagy and promotes apoptosis and sensitivity to cisplatin in oral squamous cell carcinoma. J Oral Pathol Med. 2018 Nov;47(10):930-937. doi: 10.1111/jop.12769. Epub 2018 Aug 27.
• Ref 2: MicroRNA-1 overexpression increases chemosensitivity of non-small cell lung cancer cells by inhibiting autophagy related 3-mediated autophagy. Cell Biol Int. 2018 Sep;42(9):1240-1249. doi: 10.1002/cbin.10995. Epub 2018 Jun 15.