Recombinant Human Acetyl-CoA carboxylase 1 (ACACA), partial

Function

Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). 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 (PubMed:20457939, PubMed:20952656, PubMed:29899443)

Subcellular Location

Cytoplasm, cytosol

Disease Association

Acetyl-CoA carboxylase-alpha deficiency (ACACAD) : An autosomal recessive inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in brain, placenta, skeletal muscle, renal, pancreatic and adipose tissues; expressed at low level in pulmonary tissue; not detected in the liver

Subunit

Monomer, homodimer, and homotetramer (PubMed:20952656, PubMed:29899443). Can form filamentous polymers (PubMed:20457939, PubMed:20952656, PubMed:29899443). Interacts in its inactive phosphorylated form with the BRCT domains of BRCA1 which prevents ACACA dephosphorylation and inhibits lipid synthesis (PubMed:12360400, PubMed:16326698, PubMed:18452305, PubMed:29899443). Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity (PubMed:20457939)

Pathway

Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA: step 1/1

• Abu-Elheiga L. et al. Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms. — Proc. Natl. Acad. Sci. U.S.A. (1995)
• Mao J. et al. Human acetyl-CoA carboxylase 1 gene: presence of three promoters and heterogeneity at the 5'-untranslated mRNA region. — Proc. Natl. Acad. Sci. U.S.A. (2003)
• Sinilnikova O.M. et al. Acetyl-CoA carboxylase alpha gene and breast cancer susceptibility. — Carcinogenesis (2004)
• Oshikawa M. et al. Fine expression profiling of full-length transcripts using a size-unbiased cDNA library prepared with the vector-capping method. — DNA Res. (2008)
• Mural R.J. et al. PubMed: CI-56FT96O07V0QG (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Travers M.T. et al. Characterisation of an N-terminal variant of acetyl-CoA carboxylase-alpha: expression in human tissues and evolutionary aspects. — Biochim. Biophys. Acta (2003)
• Travers M.T. et al. Asymmetric expression of transcripts derived from the shared promoter between the divergently oriented ACACA and TADA2L genes. — Genomics (2005)