Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis. This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA. acetyl-CoA + ATP + hydrogencarbonate = ADP + H(+) + malonyl-CoA + phosphate Binds 2 magnesium or manganese ions per subunit. Inhibited by phosphorylation (By similarity). Citrate promotes oligomerization of the protein into filaments that correspond to the most active form of the carboxylase (By similarity). Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA: step 1/1. Monomer, homodimer, and homotetramer. Can form filamentous polymers. Interacts in its inactive phosphorylated form with the BRCT domains of BRCA1 which prevents ACACA dephosphorylation and inhibits lipid synthesis. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity. Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain. The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA. The N-terminus is blocked. Phosphorylation on Ser-1262 is required for interaction with BRCA1. Phosphorylation at Ser-79 by AMPK inactivates enzyme activity. Phosphorylated in vitro at Ser-1200 and Ser-1215 by AMPK; the relevance of phosphorylation of these sites in vivo is however unclear. The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity.