Molecule Information

General Information of the Molecule (ID: Mol04159)

• Name: Solute carrier family 27 member 3 (SLC27A3) ,Homo sapiens
• Synonyms: Arachidonate--CoA ligase; Long-chain-fatty-acid--CoA ligase; Solute carrier family 27 member 3; Very long-chain acyl-CoA synthetase homolog 3
• Molecule Type: Protein
• Gene Name: SLC27A3
• Gene ID: 11000
• Location: chrHSCHR1_1_CTG31:91055-96858[+]
• Sequence:
  MAALLLLPLLLLLPLLLLKLHLWPQLRWLPADLAFAVRALCCKRALRARALAAAAADPEG
  PEGGCSLAWRLAELAQQRAAHTFLIHGSRRFSYSEAERESNRAARAFLRALGWDWGPDGG
  DSGEGSAGEGERAAPGAGDAAAGSGAEFAGGDGAARGGGAAAPLSPGATVALLLPAGPEF
  LWLWFGLAKAGLRTAFVPTALRRGPLLHCLRSCGARALVLAPEFLESLEPDLPALRAMGL
  HLWAAGPGTHPAGISDLLAEVSAEVDGPVPGYLSSPQSITDTCLYIFTSGTTGLPKAARI
  SHLKILQCQGFYQLCGVHQEDVIYLALPLYHMSGSLLGIVGCMGIGATVVLKSKFSAGQF
  WEDCQQHRVTVFQYIGELCRYLVNQPPSKAERGHKVRLAVGSGLRPDTWERFVRRFGPLQ
  VLETYGLTEGNVATINYTGQRGAVGRASWLYKHIFPFSLIRYDVTTGEPIRDPQGHCMAT
  SPGEPGLLVAPVSQQSPFLGYAGGPELAQGKLLKDVFRPGDVFFNTGDLLVCDDQGFLRF
  HDRTGDTFRWKGENVATTEVAEVFEALDFLQEVNVYGVTVPGHEGRAGMAALVLRPPHAL
  DLMQLYTHVSENLPPYARPRFLRLQESLATTETFKQQKVRMANEGFDPSTLSDPLYVLDQ
  AVGAYLPLTTARYSALLAGNLRI
• Function: Mainly functions as an acyl-CoA ligase catalyzing the ATP- dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates (PubMed:23936004). Can mediate the levels of long-chain fatty acids (LCFA) in the cell by facilitating their transport across membranes (By similarity). .
• Uniprot ID: S27A3_HUMAN
• Ensembl ID: ENSG00000263163
• HGNC ID: HGNC:10997

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) 1 drug(s) in total

Pazopanib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Clear cell renal cell carcinoma [ICD-11: 2C90.Y] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Resistant Drug: Pazopanib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Clear cell renal cell carcinoma
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.32E-27; Fold-change: 4.34E-01; Z-score: 1.28E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: JAK-STAT signaling pathway; Activation; hsa04630
• Cell Pathway Regulation: Insulin resistance; Activation; hsa04931
• In Vitro Model: 769-P cells; Kidney; Homo sapiens (Human); CVCL_1050
• In Vitro Model: 769-P cells with SLC27A3 up-regulation; Kidney; Homo sapiens (Human); CVCL_1050
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: 786-O cells with SLC27A3 up-regulation; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: SLC27A3 is up-regulated in pazopanib-resistant ccRCC and predicts poor prognosis. High expression of SLC27A3 produces excessive metabolites of various long-chain fatty acyl-CoA (12:0-, 16:0-, 17:0-, 20:3-CoA) to enter mitochondria for beta-oxidation and produce amounts of ROS activating mitophagy. Subsequent mitophagy/ROS negative feedback controls ROS homeostasis and consumes CPT1A protein within mitochondria to suppress fatty acid beta-oxidation, forcing acyl-CoA storage in LDs, mediating pazopanib resistance in ccRCC.

Disease Class: Clear cell renal cell carcinoma [ICD-11: 2C90.Y] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Resistant Drug: Pazopanib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Clear cell renal cell carcinoma
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.32E-27; Fold-change: 4.34E-01; Z-score: 1.28E+01
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAK-STAT signaling pathway; Activation; hsa04630
• Cell Pathway Regulation: Insulin resistance; Activation; hsa04931
• In Vivo Model: Patients with lower SLC27A3 expression; Homo Sapiens
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Overall survival assay (OS); Progression-free interval assay (PFI); Disease-specific survival assay (DSS)
• Mechanism Description: SLC27A3 is up-regulated in pazopanib-resistant ccRCC and predicts poor prognosis. High expression of SLC27A3 produces excessive metabolites of various long-chain fatty acyl-CoA (12:0-, 16:0-, 17:0-, 20:3-CoA) to enter mitochondria for beta-oxidation and produce amounts of ROS activating mitophagy. Subsequent mitophagy/ROS negative feedback controls ROS homeostasis and consumes CPT1A protein within mitochondria to suppress fatty acid beta-oxidation, forcing acyl-CoA storage in LDs, mediating pazopanib resistance in ccRCC.

Disease Class: Clear cell renal cell carcinoma [ICD-11: 2C90.Y] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Resistant Drug: Pazopanib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Clear cell renal cell carcinoma
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.32E-27; Fold-change: 4.34E-01; Z-score: 1.28E+01
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAK-STAT signaling pathway; Activation; hsa04630
• Cell Pathway Regulation: Insulin resistance; Activation; hsa04931
• In Vivo Model: Patients with higher SLC27A3 expression; Homo Sapiens
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Overall survival assay (OS); Progression-free interval assay (PFI); Disease-specific survival assay (DSS)
• Mechanism Description: SLC27A3 is up-regulated in pazopanib-resistant ccRCC and predicts poor prognosis. High expression of SLC27A3 produces excessive metabolites of various long-chain fatty acyl-CoA (12:0-, 16:0-, 17:0-, 20:3-CoA) to enter mitochondria for beta-oxidation and produce amounts of ROS activating mitophagy. Subsequent mitophagy/ROS negative feedback controls ROS homeostasis and consumes CPT1A protein within mitochondria to suppress fatty acid beta-oxidation, forcing acyl-CoA storage in LDs, mediating pazopanib resistance in ccRCC.

References

• Ref 1: STAT2/SLC27A3/PINK1-Mediated Mitophagy Remodeling Lipid Metabolism Contributes to Pazopanib Resistance in Clear Cell Renal Cell Carcinoma. Research (Wash D C). 2024 Nov 26;7:0539.