Molecule Information

General Information of the Molecule (ID: Mol04014)

• Name: Apolipoprotein C-II (APOC2) ,Homo sapiens
• Synonyms: Apolipoprotein C3
• Molecule Type: Protein
• Gene Name: APOC3
• Gene ID: 345
• Location: chr11:116829706-116833072[+]
• Sequence:
  MQPRVLLVVALLALLASARASEAEDASLLSFMQGYMKHATKTAKDALSSVQESQVAQQAR
  GWVTDGFSSLKDYWSTVKDKFSEFWDLDPEVRPTSAVAA
• 3D-structure: PDB ID: 2JQ3; Classification: Lipid binding protein; Method: Solution nmr; Resolution: No Resolution Dat Å
• Function: Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma (PubMed:18201179, PubMed:22510806). Plays a multifaceted role in triglyceride homeostasis (PubMed:18201179, PubMed:22510806). Intracellularly, promotes hepatic very low density lipoprotein 1 (VLDL1) assembly and secretion; extracellularly, attenuates hydrolysis and clearance of triglyceride- rich lipoproteins (TRLs) (PubMed:18201179, PubMed:22510806). Impairs the lipolysis of TRLs by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors (PubMed:18201179, PubMed:22510806). Formed of several curved helices connected via semiflexible hinges, so that it can wrap tightly around the curved micelle surface and easily adapt to the different diameters of its natural binding partners (PubMed:18408013). .
• Uniprot ID: APOC3_HUMAN
• Ensembl ID: ENSG00000110245
• HGNC ID: HGNC:610

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

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Anti-isotype IgG mAb

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Anti-isotype IgG mAb
• Molecule Alteration: Lactylation; K70
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Flag-tagged APOC2-K70R mice; Mice
• Experiment for Molecule Alteration: Mass spectrometry analysis
• Experiment for Drug Resistance: Tumor growth assay
• Mechanism Description: Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Sensitive Drug: Anti-isotype IgG mAb
• Molecule Alteration: Lactylation; K70
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Flag-tagged APOC2-WT mice; Mice
• Experiment for Molecule Alteration: Mass spectrometry analysis
• Experiment for Drug Resistance: Tumor growth assay
• Mechanism Description: Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis.

Anti-PD-1 mAb

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Anti-PD-1 mAb
• Molecule Alteration: Lactylation; K70
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Breast cancers; Homo Sapiens
• Experiment for Molecule Alteration: Mass spectrometry analysis
• Experiment for Drug Resistance: Western blot assay
• Mechanism Description: Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis.

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Anti-PD-1 mAb
• Molecule Alteration: Lactylation; K70
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Gastric cancers; Homo Sapiens
• Experiment for Molecule Alteration: Mass spectrometry analysis
• Experiment for Drug Resistance: Western blot assay
• Mechanism Description: Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis.

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Anti-PD-1 mAb
• Molecule Alteration: Lactylation; K70
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Flag-tagged APOC2-K70R mice; Mice
• Experiment for Molecule Alteration: Mass spectrometry analysis
• Experiment for Drug Resistance: Tumor growth assay
• Mechanism Description: Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Sensitive Drug: Anti-PD-1 mAb
• Molecule Alteration: Lactylation; K70
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Flag-tagged APOC2-WT mice; Mice
• Experiment for Molecule Alteration: Mass spectrometry analysis
• Experiment for Drug Resistance: Tumor growth assay
• Mechanism Description: Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis.

References

• Ref 1: Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis. Adv Sci (Weinh). 2024 Oct;11(38):e2406333.