Molecule Information

General Information of the Molecule (ID: Mol04433)
Name
Acetyl-CoA acetyltransferase, cytosolic (ACAT2) ,Homo sapiens
Synonyms
Acetyl-CoA transferase-like protein; Cytosolic acetoacetyl-CoA thiolase
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Molecule Type
Protein
Gene Name
ACAT2
Gene ID
39
Sequence
MNAGSDPVVIVSAARTIIGSFNGALAAVPVQDLGSTVIKEVLKRATVAPEDVSEVIFGHV
LAAGCGQNPVRQASVGAGIPYSVPAWSCQMICGSGLKAVCLAVQSIGIGDSSIVVAGGM
E NMSKAPHLAYLRTGVKIGEMPLTDSILCDGLTDAFHNCHMGITAENVAKKWQVSREDQ
DK VAVLSQNRTENAQKAGHFDKEIVPVLVSTRKGLIEVKTDEFPRHGSNIEAMSKLKPY
FLT DGTGTVTPANASGINDGAAAVVLMKKSEADKRGLTPLARIVSWSQVGVEPSIMGIG
PIPA IKQAVTKAGWSLEDVDIFEINEAFAAVSAAIVKELGLNPEKVNIEGGAIALGHPL
GASGC RILVTLLHTLERMGRSRGVAALCIGGGMGIAMCVQRE
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Function
Involved in the biosynthetic pathway of cholesterol.{ECO:0000303|PubMed:15733928}.
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Uniprot ID
THIC_HUMAN
Ensembl ID
ENSG000001204379
HGNC ID
HGNC:94
        Click to Show/Hide the Complete Species Lineage
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
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Cisplatin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Bladder cancer [ICD-11: 2C94.0] [1]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Fatty acid biosynthesis Activation hsa00061
In Vitro Model J82 cells Bladder Homo sapiens (Human) CVCL_0359
Experiment for
Molecule Alteration		 Western blot assay
Experiment for
Drug Resistance		 Trypan blue exclusion assay; XTT assay
Mechanism Description Metabolomics analyses in our lab's gemcitabine- and cisplatin-resistant cell lines revealed increased phosphoglycerate dehydrogenase (PHGDH) expression in gemcitabine-resistant cells compared with parental cells. Isocitrate dehydrogenase 2 (IDH2) gain of function stabilized hypoxia-inducible factor1alpha (HIF1alpha) expression, stimulating aerobic glycolysis. In gemcitabine-resistant cells, elevated fumaric acid suppressed prolyl hydroxylase domain-containing protein 2/Egl nine homolog 1 (PHD2) and stabilized?HIF1alpha?expression.?PHGDH?downregulation or inhibition in gemcitabine-resistant BC cells inhibited their proliferation, migration, and invasion. Cisplatin-resistant cells showed elevated fatty acid metabolism, upregulating fatty acid synthase (FASN) downstream of tyrosine kinase. Using the fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor erdafitinib, we inhibited malonyl-CoA production, which is crucial for fatty acid synthesis, and thereby suppressed upregulated HIF1alpha expression.
References
Ref 1 Targeting metabolic reprogramming to overcome drug resistance in advanced bladder cancer: insights from gemcitabine- and cisplatin-resistant models. Mol Oncol. 2024 Sep;18(9):2196-2211.

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