ACACB

ACACB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DN8, 2HJW, 2KCC, 3FF6, 3GID, 3GLK, 3JRW, 3JRX, 3TDC, 4HQ6, 5KKN
Identifiers
Aliases	ACACB, ACC2, ACCB, HACC275, acetyl-CoA carboxylase beta, ACC-beta, ACCbeta, ACACbeta
External IDs	OMIM: 601557 MGI: 2140940 HomoloGene: 74382 GeneCards: ACACB
Gene location (Human) Chr. Chromosome 12 (human) Band 12q24.11 Start 109,116,587 bp End 109,268,226 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 F Start 114,284,596 bp End 114,388,822 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in adipose tissue subcutaneous adipose tissue gastric mucosa renal medulla abdominal fat pericardium gastrocnemius muscle internal globus pallidus sural nerve skeletal muscle tissue Top expressed in brown adipose tissue interventricular septum right ventricle myocardium of ventricle intercostal muscle skeletal muscle tissue gastrocnemius muscle extraocular muscle digastric muscle triceps brachii muscle More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding metal ion binding biotin carboxylase activity ligase activity protein binding catalytic activity ATP binding biotin binding identical protein binding acetyl-CoA carboxylase complex acetyl-CoA carboxylase activity Cellular component cytosol membrane mitochondrial outer membrane mitochondrion endomembrane system nucleus Biological process carnitine shuttle malonyl-CoA biosynthetic process negative regulation of catalytic activity lipid metabolism negative regulation of fatty acid oxidation positive regulation of lipid storage negative regulation of gene expression fatty acid metabolic process positive regulation of heart growth negative regulation of fatty acid beta-oxidation regulation of glucose metabolic process fatty acid biosynthetic process response to nutrient levels energy homeostasis metabolism positive regulation of cellular metabolic process negative regulation of lipid catabolic process protein homotetramerization acetyl-CoA metabolic process response to organic cyclic compound regulation of cholesterol biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 32 100705 Ensembl ENSG00000076555 ENSMUSG00000042010 UniProt O00763 E9Q4Z2 RefSeq (mRNA) NM_001093 NM_133904 RefSeq (protein) NP_001084 NP_598665 NP_001390456 NP_001390457 NP_001390458 Location (UCSC) Chr 12: 109.12 – 109.27 Mb Chr 5: 114.28 – 114.39 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Acetyl-CoA carboxylase 2 also known as ACC-beta or ACC2 is an enzyme that in humans is encoded by the ACACB gene.

Function

Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine palmitoyltransferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis.

Clinical implications

Human acetyl-CoA carboxylase has recently become a target in the design of new anti-obesity drugs. However, when the gene for ACC2 was knocked out in mice, no change in body weight was observed relative to normal mice. This result suggests inhibition of ACC2 by drugs may be an ineffective method of treating obesity.

Further reading

• Cheng D, Chu CH, Chen L, Feder JN, Mintier GA, Wu Y, Cook JW, Harpel MR, Locke GA, An Y, Tamura JK (January 2007). "Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes". Protein Expression and Purification. 51 (1): 11–21. doi:10.1016/j.pep.2006.06.005. PMID 16854592.
• Diaz FJ, Meary A, Arranz MJ, Ruaño G, Windemuth A, de Leon J (December 2009). "Acetyl-coenzyme A carboxylase alpha gene variations may be associated with the direct effects of some antipsychotics on triglyceride levels". Schizophrenia Research. 115 (2–3): 136–40. doi:10.1016/j.schres.2009.09.038. PMC 2784140. PMID 19846279.
• Madauss KP, Burkhart WA, Consler TG, Cowan DJ, Gottschalk WK, Miller AB, Short SA, Tran TB, Williams SP (May 2009). "The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist". Acta Crystallographica Section D. 65 (Pt 5): 449–61. Bibcode:2009AcCrD..65..449M. doi:10.1107/S0907444909008014. PMC 2725780. PMID 19390150.
• Kahn BB, Alquier T, Carling D, Hardie DG (January 2005). "AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism". Cell Metabolism. 1 (1): 15–25. doi:10.1016/j.cmet.2004.12.003. PMID 16054041.
• de Leon J, Correa JC, Ruaño G, Windemuth A, Arranz MJ, Diaz FJ (January 2008). "Exploring genetic variations that may be associated with the direct effects of some antipsychotics on lipid levels". Schizophrenia Research. 98 (1–3): 40–6. doi:10.1016/j.schres.2007.10.003. PMID 18031993. S2CID 26681612.
• Kreuz S, Schoelch C, Thomas L, Rist W, Rippmann JF, Neubauer H (September 2009). "Acetyl-CoA carboxylases 1 and 2 show distinct expression patterns in rats and humans and alterations in obesity and diabetes". Diabetes/Metabolism Research and Reviews. 25 (6): 577–86. doi:10.1002/dmrr.997. PMID 19618481. S2CID 33291872.
• Castle JC, Hara Y, Raymond CK, Garrett-Engele P, Ohwaki K, Kan Z, Kusunoki J, Johnson JM (2009). Zanger U (ed.). "ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus [corrected]". PLOS ONE. 4 (2): e4369. doi:10.1371/journal.pone.0004369. PMC 2629817. PMID 19190759.
• Højlund K, Mustard KJ, Staehr P, Hardie DG, Beck-Nielsen H, Richter EA, Wojtaszewski JF (February 2004). "AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes". American Journal of Physiology. Endocrinology and Metabolism. 286 (2): E239-44. doi:10.1152/ajpendo.00326.2003. PMID 14532170.
• Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H (March 2008). "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics. 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
• Szabo de Edelenyi F, Goumidi L, Bertrais S, Phillips C, Macmanus R, Roche H, Planells R, Lairon D (December 2008). "Prediction of the metabolic syndrome status based on dietary and genetic parameters, using Random Forest". Genes & Nutrition. 3 (3–4): 173–6. doi:10.1007/s12263-008-0097-y. PMC 2593021. PMID 19034549.
• Conde E, Suarez-Gauthier A, García-García E, Lopez-Rios F, Lopez-Encuentra A, García-Lujan R, Morente M, Sanchez-Verde L, Sanchez-Cespedes M (September 2007). "Specific pattern of LKB1 and phospho-acetyl-CoA carboxylase protein immunostaining in human normal tissues and lung carcinomas". Human Pathology. 38 (9): 1351–60. doi:10.1016/j.humpath.2007.01.022. PMID 17521700.
• Rosa G, Manco M, Vega N, Greco AV, Castagneto M, Vidal H, Mingrone G (November 2003). "Decreased muscle acetyl-coenzyme A carboxylase 2 mRNA and insulin resistance in formerly obese subjects". Obesity Research. 11 (11): 1306–12. doi:10.1038/oby.2003.177. PMID 14627750.
• Oh SY, Lee MY, Kim JM, Yoon S, Shin S, Park YN, Ahn YH, Kim KS (February 2005). "Alternative usages of multiple promoters of the acetyl-CoA carboxylase beta gene are related to differential transcriptional regulation in human and rodent tissues". The Journal of Biological Chemistry. 280 (7): 5909–16. doi:10.1074/jbc.M409037200. PMID 15590647.
• Locke GA, Cheng D, Witmer MR, Tamura JK, Haque T, Carney RF, Rendina AR, Marcinkeviciene J (July 2008). "Differential activation of recombinant human acetyl-CoA carboxylases 1 and 2 by citrate". Archives of Biochemistry and Biophysics. 475 (1): 72–9. doi:10.1016/j.abb.2008.04.011. PMID 18455495.
• Cho YS, Lee JI, Shin D, Kim HT, Jung HY, Lee TG, Kang LW, Ahn YJ, Cho HS, Heo YS (January 2010). "Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK". Biochemical and Biophysical Research Communications. 391 (1): 187–92. doi:10.1016/j.bbrc.2009.11.029. PMID 19900410.
• Frøsig C, Jørgensen SB, Hardie DG, Richter EA, Wojtaszewski JF (March 2004). "5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle". American Journal of Physiology. Endocrinology and Metabolism. 286 (3): E411-7. doi:10.1152/ajpendo.00317.2003. PMID 14613924.
• Ruaño G, Bernene J, Windemuth A, Bower B, Wencker D, Seip RL, Kocherla M, Holford TR, Petit WA, Hanks S (February 2009). "Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone". Clinica Chimica Acta; International Journal of Clinical Chemistry. 400 (1–2): 48–55. doi:10.1016/j.cca.2008.10.009. PMID 18996102.
• Kim KW, Yamane H, Zondlo J, Busby J, Wang M (May 2007). "Expression, purification, and characterization of human acetyl-CoA carboxylase 2". Protein Expression and Purification. 53 (1): 16–23. doi:10.1016/j.pep.2006.11.021. PMID 17223360.
• Ruderman N, Prentki M (April 2004). "AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome". Nature Reviews. Drug Discovery. 3 (4): 340–51. doi:10.1038/nrd1344. PMID 15060529. S2CID 36977305.

External links

• Human ACACB genome location and ACACB gene details page in the UCSC Genome Browser.