ACACB: Acetyl-CoA Carboxylase Beta
Key regulator of fatty acid oxidation and metabolic homeostasis
Gene Information Card
| Symbol | ACACB |
|---|---|
| Full Name | Acetyl-CoA Carboxylase Beta |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.11 |
| NCBI Gene ID | 32 ncbi.nlm.nih.gov/gene/32 |
| Ensembl ID | ENSG00000076555 |
| UniProt ID | O00763 |
| OMIM ID | 601557 |
| HGNC ID | 85 |
| Aliases | ACC2, ACC-beta, HACC275 |
Description
ACACB encodes acetyl-CoA carboxylase beta (ACC2), a mitochondrial membrane-bound enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA. Malonyl-CoA inhibits carnitine palmitoyltransferase 1 (CPT1), thereby regulating fatty acid oxidation. ACC2 is a key metabolic sensor and target of AMPK phosphorylation. The gene is implicated in energy homeostasis, insulin resistance, and obesity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | Increased ACC2 activity elevates malonyl-CoA, suppressing fatty acid oxidation and promoting lipid storage. | PMID: 16959974; GWAS catalog |
| Type 2 Diabetes | Dysregulation of ACC2 contributes to insulin resistance via impaired fatty acid oxidation and lipid accumulation in muscle and liver. | PMID: 16959974; ClinVar |
| Metabolic Syndrome | Altered ACC2 expression correlates with hyperlipidemia and hepatic steatosis. | PMID: 20074554 |
| Cardiovascular Disease | ACC2-mediated lipid metabolism influences atherosclerosis risk. | PMID: 20074554 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 8.2 | Medium |
| Skeletal Muscle | 12.5 | High |
| Adipose Tissue | 6.1 | Medium |
| Heart | 9.8 | High |
| Kidney | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 7.5 | Hepatocellular carcinoma cell line |
| C2C12 | 14.0 | Mouse myoblast; high ACC2 expression |
| 3T3-L1 | 5.8 | Adipocyte precursor; moderate expression |
| HEK293 | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1342C>T (p.Arg448Trp) | Missense | 0.001% (gnomAD) | Reduced enzyme activity; associated with altered lipid metabolism |
| c.2155G>A (p.Gly719Ser) | Missense | 0.002% (gnomAD) | Impaired AMPK phosphorylation site; potential gain-of-function |
| c.3010C>T (p.Arg1004*) | Nonsense | <0.001% | Loss-of-function; rare in population |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg1004*) lead to truncated protein lacking catalytic domain, reducing malonyl-CoA production and increasing fatty acid oxidation.
Gain of Function (GOF)
Missense mutations at regulatory phosphorylation sites (e.g., p.Gly719Ser) may impair AMPK inhibition, causing constitutive activity and elevated malonyl-CoA.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for ACACB.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003989 - acetyl-CoA carboxylase activity | • GO:0005524 - ATP binding |
| • GO:0006633 - fatty acid biosynthetic process | • GO:0014070 - response to organic cyclic compound |
| • GO:0042593 - glucose homeostasis | • GO:0005739 - mitochondrion |
Pathways
• Fatty acid biosynthesis (Reactome R-HSA-75105)
• Metabolism of lipids (Reactome R-HSA-556833)
• AMPK signaling pathway (KEGG hsa04152)
• Insulin signaling pathway (KEGG hsa04910)
Protein Summary
Acetyl-CoA carboxylase beta (ACC2) is a 2458-amino acid mitochondrial membrane protein that catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. It contains a biotin carboxylase domain, a carboxyltransferase domain, and a C-terminal biotin-binding domain. ACC2 is regulated by AMPK phosphorylation at Ser221, which inhibits its activity. Unlike the cytosolic ACC1, ACC2 is primarily involved in controlling fatty acid oxidation by producing malonyl-CoA that allosterically inhibits CPT1 at the mitochondrial membrane. ACC2 is highly expressed in oxidative tissues such as heart, skeletal muscle, and liver.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACACB Knockout HEK293 Cell Line | EDJ-KQ1874 | Human | 32 | Details Get a Quote |
| ACACB Knockout A-549 Cell Line | EDC90087 | Human | 32 | Details Get a Quote |
| ACACB Knockout HCT 116 Cell Line | EDJ-KQ21753 | Human | 32 | Details Get a Quote |
| ACACB Knockout HeLa Cell Line | EDJ-KQ21754 | Human | 32 | Details Get a Quote |
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