MitoProteome Database

MT000005

UniProt Annotations

Entry Information

Gene Name	acetyl-CoA carboxylase beta
Protein Entry	ACACB_HUMAN
UniProt ID	O00763
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=Long; IsoId=O00763-1; Sequence=Displayed; Name=2; Synonyms=Short; IsoId=O00763-2; Sequence=VSP_000547; Name=3 {ECO:0000305}; Synonyms=ACC2.v2 {ECO:0000303\|PubMed:19190759}; IsoId=O00763-3; Sequence=VSP_057081, VSP_057082;
Biophysicochemical Properties	Kinetic parameters: KM=120 uM for ATP {ECO:0000269\|PubMed:16854592}; KM=110 uM for ATP (isoform 2) {ECO:0000269\|PubMed:19190759}; KM=58 uM for acetyl-CoA {ECO:0000269\|PubMed:16854592}; KM=94 uM for acetyl-CoA (isoform 3) {ECO:0000269\|PubMed:19190759}; KM=6.5 mM for NaHCO3 (isoform 3) {ECO:0000269\|PubMed:19190759}; KM=3.0 mM for NaHCO(3) {ECO:0000269\|PubMed:16854592};
Biotechnology	Inhibition of ACACB may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme a potential pharmaceutical target for treatment of obesity and type 2 diabetes. {ECO:0000305}.
Catalytic Activity	ATP + acetyl-CoA + HCO(3)(-) = ADP + phosphate + malonyl-CoA. {ECO:0000269\|PubMed:16854592, ECO:0000269\|PubMed:20952656}.
Catalytic Activity	ATP + biotin-[carboxyl-carrier-protein] + CO(2) = ADP + phosphate + carboxy-biotin-[carboxyl-carrier- protein]. {ECO:0000250}.
Cofactor	Name=biotin; Xref=ChEBI:CHEBI:57586; Evidence={ECO:0000250}; Note=Biotin. {ECO:0000250};
Cofactor	Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; Note=Binds 2 manganese ions per subunit. {ECO:0000250};
Enzyme Regulation	Activity is increased by oligomerization. Activated by citrate. Citrate and MID1IP1 promote oligomerization. Inhibited by malonyl-CoA. {ECO:0000269\|PubMed:16854592, ECO:0000269\|PubMed:20952656}.
Function	Catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in inhibition of fatty acid and glucose oxidation and enhancement of fat storage (By similarity). May play a role in regulation of mitochondrial fatty acid oxidation through malonyl- CoA-dependent inhibition of carnitine palmitoyltransferase 1 (By similarity). {ECO:0000250\|UniProtKB:E9Q4Z2, ECO:0000269\|PubMed:20952656}.
Interaction	P50747:HLCS; NbExp=4; IntAct=EBI-2211739, EBI-3915568;
Pathway	Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA: step 1/1.
Ptm	Phosphorylated by AMPK, leading to inactivation of the enzyme. Required for the maintenance of skeletal muscle lipid and glucose homeostasis (By similarity). {ECO:0000250\|UniProtKB:E9Q4Z2, ECO:0000269\|PubMed:12488245}.
Sequence Caution	Sequence=AAB58382.1; Type=Miscellaneous discrepancy; Note=Many Frameshifts and conflicts.; Evidence={ECO:0000305}; Sequence=CAE01470.2; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
Similarity	Contains 1 ATP-grasp domain. {ECO:0000255\|PROSITE- ProRule:PRU00409}.
Similarity	Contains 1 biotin carboxylation domain. {ECO:0000305}.
Similarity	Contains 1 biotinyl-binding domain. {ECO:0000255\|PROSITE-ProRule:PRU01066, ECO:0000305}.
Similarity	Contains 1 carboxyltransferase domain. {ECO:0000305}.
Subcellular Location	Mitochondrion {ECO:0000269\|PubMed:10677481}. Nucleus {ECO:0000269\|PubMed:10677481}. Endomembrane system. Note=May associate with membranes.
Subunit	Monomer, homodimer, and homotetramer. Can form filamentous polymers. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity. {ECO:0000269\|PubMed:20952656}.
Tissue Specificity	Widely expressed with highest levels in heart, skeletal muscle, liver, adipose tissue, mammary gland, adrenal gland and colon (PubMed:9099716). Isoform 3 is expressed in skeletal muscle, adipose tissue and liver (at protein level) (PubMed:19190759). Isoform 3 is detected at high levels in adipose tissue with lower levels in heart, liver, skeletal muscle and testis (PubMed:19190759). {ECO:0000269\|PubMed:19190759, ECO:0000269\|PubMed:9099716}.