Acetyl-CoA carboxylase 1

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. 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.

Classification

Family (Pfam)

PF08326 ACC_central, PF21385 ACCA_BT, PF02785 Biotin_carb_C, PF00289 Biotin_carb_N, PF00364 Biotin_lipoyl, PF01039 Carboxyl_trans, PF02786 CPSase_L_D2

InterPro

ACCA, ACCA_BT, AcCoA_carboxyl_beta, AcCoA_COase_cen, ATP-grasp, ATP_grasp_subdomain_1, BC-like_N, Biotin_BS, Biotin_carboxylation_dom, Biotin_COase_C, Biotin_lipoyl, ClpP/crotonase-like_dom_sf, COA_CT_C, COA_CT_N, CPAse_ATP-bd, PreATP-grasp_dom_sf, Rudment_hybrid_motif, Single_hybrid_motif

Functional cluster

Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 10

• 2YL2 X-ray 2.30A
• 3COJ X-ray 3.21A
• 4ASI X-ray 2.80A
• 6G2D EM 5.40A
• 6G2H EM 4.60A
• 6G2I EM 5.90A
• 8XKZ EM 2.55A
• 8XL0 EM 4.14A
• 8XL1 EM 2.57A
• 8XL2 EM 2.73A

A predicted model is available from AlphaFold.

Gene Ontology · 11

• GO:0005829 cytosol
• GO:0005739 mitochondrion
• GO:0003989 acetyl-CoA carboxylase activity
• GO:0005524 ATP binding
• GO:0042802 identical protein binding
• GO:0046872 metal ion binding
• GO:0006084 acetyl-CoA metabolic process
• GO:0006633 fatty acid biosynthetic process
• GO:0046949 fatty-acyl-CoA biosynthetic process
• GO:2001295 malonyl-CoA biosynthetic process
• GO:0051289 protein homotetramerization

Disease associations

• acetyl-coa carboxylase deficiency MONDO:0013493

Drugs targeting this protein · 4

• PF-05175157 inhibitor
• FIRSOCOSTAT negative allosteric modulator
• OLUMACOSTAT GLASARETIL inhibitor
• CLESACOSTAT inhibitor

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Acetyl-CoA carboxylase 1 1.00
• Acetyl-CoA carboxylase 1 1.00
• Acetyl-CoA carboxylase 1 1.00
• Acetyl-CoA carboxylase 1 1.00
• Acetyl-CoA carboxylase 0.99
• Acetyl-CoA carboxylase 2 0.81
• Acetyl-CoA carboxylase 2 0.79
• Pantothenate kinase 2 0.75
• Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase 0.75
• Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase 0.74
• Pyrophosphate--fructose 6-phosphate 1-phosphotransferase subunit beta 0.74
• Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase 0.73

Co-cited proteins · studied together in the literature

• Acetyl-CoA carboxylase 1 4 shared papers
• Acetyl-CoA carboxylase 1 1 shared papers
• Breast cancer type 1 susceptibility protein 4 shared papers
• Acetyl-CoA carboxylase 2 2 shared papers
• Mid1-interacting protein 1 2 shared papers
• Golgin subfamily B member 1 1 shared papers
• Breast cancer type 1 susceptibility protein homolog 1 shared papers
• Thyroid hormone-inducible hepatic protein 1 shared papers
• Filamin-B 1 shared papers

Literature · 29 cited papers

• Structural basis for regulation of human acetyl-CoA carboxylase. Nature · 2018
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Crystal structure of Spot 14, a modulator of fatty acid synthesis. Proc. Natl. Acad. Sci. U.S.A. · 2010
• Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis. Proc. Natl. Acad. Sci. U.S.A. · 2010
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• … and 17 more in the literature graph