Gene/Proteome Database (LMPD)
LMPD ID
LMP006663
Gene ID
Species
Homo sapiens (Human)
Gene Name
acetyl-CoA carboxylase beta
Gene Symbol
Synonyms
ACC2; ACCB; HACC275
Alternate Names
acetyl-CoA carboxylase 2; ACC-beta; acetyl-Coenzyme A carboxylase beta
Chromosome
12
Map Location
12q24.11
EC Number
6.4.1.2
Summary
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-palmitoyl-CoA transferase 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. There is evidence for the presence of two ACC-beta isoforms. [provided by RefSeq, Jul 2008]
Orthologs
Proteins
| acetyl-CoA carboxylase 2 precursor | |
|---|---|
| Refseq ID | NP_001084 |
| Protein GI | 134142062 |
| UniProt ID | O00763 |
| mRNA ID | NM_001093 |
| Length | 2458 |
| RefSeq Status | REVIEWED |
| MVLLLCLSCLIFSCLTFSWLKIWGKMTDSKPITKSKSEANLIPSQEPFPASDNSGETPQRNGEGHTLPKTPSQAEPASHKGPKDAGRRRNSLPPSHQKPPRNPLSSSDAAPSPELQANGTGTQGLEATDTNGLSSSARPQGQQAGSPSKEDKKQANIKRQLMTNFILGSFDDYSSDEDSVAGSSRESTRKGSRASLGALSLEAYLTTGEAETRVPTMRPSMSGLHLVKRGREHKKLDLHRDFTVASPAEFVTRFGGDRVIEKVLIANNGIAAVKCMRSIRRWAYEMFRNERAIRFVVMVTPEDLKANAEYIKMADHYVPVPGGPNNNNYANVELIVDIAKRIPVQAVWAGWGHASENPKLPELLCKNGVAFLGPPSEAMWALGDKIASTVVAQTLQVPTLPWSGSGLTVEWTEDDLQQGKRISVPEDVYDKGCVKDVDEGLEAAERIGFPLMIKASEGGGGKGIRKAESAEDFPILFRQVQSEIPGSPIFLMKLAQHARHLEVQILADQYGNAVSLFGRDCSIQRRHQKIVEEAPATIAPLAIFEFMEQCAIRLAKTVGYVSAGTVEYLYSQDGSFHFLELNPRLQVEHPCTEMIADVNLPAAQLQIAMGVPLHRLKDIRLLYGESPWGVTPISFETPSNPPLARGHVIAARITSENPDEGFKPSSGTVQELNFRSSKNVWGYFSVAATGGLHEFADSQFGHCFSWGENREEAISNMVVALKELSIRGDFRTTVEYLINLLETESFQNNDIDTGWLDYLIAEKVQAEKPDIMLGVVCGALNVADAMFRTCMTDFLHSLERGQVLPADSLLNLVDVELIYGGVKYILKVARQSLTMFVLIMNGCHIEIDAHRLNDGGLLLSYNGNSYTTYMKEEVDSYRITIGNKTCVFEKENDPTVLRSPSAGKLTQYTVEDGGHVEAGSSYAEMEVMKMIMTLNVQERGRVKYIKRPGAVLEAGCVVARLELDDPSKVHPAEPFTGELPAQQTLPILGEKLHQVFHSVLENLTNVMSGFCLPEPVFSIKLKEWVQKLMMTLRHPSLPLLELQEIMTSVAGRIPAPVEKSVRRVMAQYASNITSVLCQFPSQQIATILDCHAATLQRKADREVFFINTQSIVQLVQRYRSGIRGYMKTVVLDLLRRYLRVEHHFQQAHYDKCVINLREQFKPDMSQVLDCIFSHAQVAKKNQLVIMLIDELCGPDPSLSDELISILNELTQLSKSEHCKVALRARQILIASHLPSYELRHNQVESIFLSAIDMYGHQFCPENLKKLILSETTIFDVLPTFFYHANKVVCMASLEVYVRRGYIAYELNSLQHRQLPDGTCVVEFQFMLPSSHPNRMTVPISITNPDLLRHSTELFMDSGFSPLCQRMGAMVAFRRFEDFTRNFDEVISCFANVPKDTPLFSEARTSLYSEDDCKSLREEPIHILNVSIQCADHLEDEALVPILRTFVQSKKNILVDYGLRRITFLIAQEKEFPKFFTFRARDEFAEDRIYRHLEPALAFQLELNRMRNFDLTAVPCANHKMHLYLGAAKVKEGVEVTDHRFFIRAIIRHSDLITKEASFEYLQNEGERLLLEAMDELEVAFNNTSVRTDCNHIFLNFVPTVIMDPFKIEESVRYMVMRYGSRLWKLRVLQAEVKINIRQTTTGSAVPIRLFITNESGYYLDISLYKEVTDSRSGNIMFHSFGNKQGPQHGMLINTPYVTKDLLQAKRFQAQTLGTTYIYDFPEMFRQALFKLWGSPDKYPKDILTYTELVLDSQGQLVEMNRLPGGNEVGMVAFKMRFKTQEYPEGRDVIVIGNDITFRIGSFGPGEDLLYLRASEMARAEGIPKIYVAANSGARIGMAEEIKHMFHVAWVDPEDPHKGFKYLYLTPQDYTRISSLNSVHCKHIEEGGESRYMITDIIGKDDGLGVENLRGSGMIAGESSLAYEEIVTISLVTCRAIGIGAYLVRLGQRVIQVENSHIILTGASALNKVLGREVYTSNNQLGGVQIMHYNGVSHITVPDDFEGVYTILEWLSYMPKDNHSPVPIITPTDPIDREIEFLPSRAPYDPRWMLAGRPHPTLKGTWQSGFFDHGSFKEIMAPWAQTVVTGRARLGGIPVGVIAVETRTVEVAVPADPANLDSEAKIIQQAGQVWFPDSAYKTAQAVKDFNREKLPLMIFANWRGFSGGMKDMYDQVLKFGAYIVDGLRQYKQPILIYIPPYAELRGGSWVVIDATINPLCIEMYADKESRGGVLEPEGTVEIKFRKKDLIKSMRRIDPAYKKLMEQLGEPDLSDKDRKDLEGRLKAREDLLLPIYHQVAVQFADFHDTPGRMLEKGVISDILEWKTARTFLYWRLRRLLLEDQVKQEILQASGELSHVHIQSMLRRWFVETEGAVKAYLWDNNQVVVQWLEQHWQAGDGPRSTIRENITYLKHDSVLKTIRGLVEENPEVAVDCVIYLSQHISPAERAQVVHLLSTMDSPAST | |
| sig_peptide: 1..16 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1772 peptide sequence: MVLLLCLSCLIFSCLT | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005829 | TAS:Reactome | C | cytosol |
| GO:0005741 | TAS:Reactome | C | mitochondrial outer membrane |
| GO:0005739 | IDA:UniProtKB | C | mitochondrion |
| GO:0005634 | IDA:UniProtKB | C | nucleus |
| GO:0005524 | IEA:UniProtKB-KW | F | ATP binding |
| GO:0003989 | IDA:UniProtKB | F | acetyl-CoA carboxylase activity |
| GO:0009374 | IEA:Ensembl | F | biotin binding |
| GO:0004075 | IEA:UniProtKB-EC | F | biotin carboxylase activity |
| GO:0046872 | IEA:UniProtKB-KW | F | metal ion binding |
| GO:0006084 | IDA:UniProtKB | P | acetyl-CoA metabolic process |
| GO:0006768 | TAS:Reactome | P | biotin metabolic process |
| GO:0006853 | TAS:Reactome | P | carnitine shuttle |
| GO:0044255 | TAS:Reactome | P | cellular lipid metabolic process |
| GO:0006112 | TAS:Reactome | P | energy reserve metabolic process |
| GO:0006633 | IEA:UniProtKB-KW | P | fatty acid biosynthetic process |
| GO:2001295 | IEA:UniProtKB-UniPathway | P | malonyl-CoA biosynthetic process |
| GO:0031325 | TAS:Reactome | P | positive regulation of cellular metabolic process |
| GO:0051289 | IDA:UniProtKB | P | protein homotetramerization |
| GO:0042493 | IEA:Ensembl | P | response to drug |
| GO:0014070 | IEA:Ensembl | P | response to organic cyclic compound |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
| GO:0006766 | TAS:Reactome | P | vitamin metabolic process |
| GO:0006767 | TAS:Reactome | P | water-soluble vitamin metabolic process |
KEGG Pathway Links
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR011761 | ATP-grasp fold |
| IPR013815 | ATP-grasp fold, subdomain 1 |
| IPR013816 | ATP-grasp fold, subdomain 2 |
| IPR013537 | Acetyl-CoA carboxylase, central domain |
| IPR011763 | Acetyl-coenzyme A carboxyltransferase, C-terminal |
| IPR011762 | Acetyl-coenzyme A carboxyltransferase, N-terminal |
| IPR005482 | Biotin carboxylase, C-terminal |
| IPR011764 | Biotin carboxylation domain |
| IPR000089 | Biotin/lipoyl attachment |
| IPR005481 | Carbamoyl-phosphate synthase, large subunit, N-terminal |
| IPR005479 | Carbamoyl-phosphate synthetase large subunit-like, ATP-binding domain |
| IPR000022 | Carboxyl transferase |
| IPR029045 | ClpP/crotonase-like domain |
| IPR016185 | Pre-ATP-grasp domain |
| IPR011054 | Rudiment single hybrid motif |
| IPR011053 | Single hybrid motif |
UniProt Annotations
Entry Information
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 ; Synonyms=ACC2.v2 ; IsoId=O00763-3; Sequence=VSP_057081, VSP_057082; |
| Biophysicochemical Properties | Kinetic parameters: KM=120 uM for ATP ; KM=110 uM for ATP (isoform 2) ; KM=58 uM for acetyl-CoA ; KM=94 uM for acetyl-CoA (isoform 3) ; KM=6.5 mM for NaHCO3 (isoform 3) ; KM=3.0 mM for NaHCO(3) ; |
| 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. |
| Catalytic Activity | ATP + acetyl-CoA + HCO(3)(-) = ADP + phosphate + malonyl-CoA. {ECO |
| Catalytic Activity | ATP + biotin-[carboxyl-carrier-protein] + CO(2) = ADP + phosphate + carboxy-biotin-[carboxyl-carrier- protein]. |
| Cofactor | Name=Mn(2+); Xref=ChEBI |
| Cofactor | Name=biotin; Xref=ChEBI |
| Enzyme Regulation | Activity is increased by oligomerization. Activated by citrate. Citrate and MID1IP1 promote oligomerization. Inhibited by malonyl-CoA. {ECO |
| 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 |
| Interaction | P50747:HLCS; NbExp=4; IntAct=EBI-2211739, EBI-3915568; |
| Pathway | Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA |
| Ptm | Phosphorylated by AMPK, leading to inactivation of the enzyme. Required for the maintenance of skeletal muscle lipid and glucose homeostasis (By similarity). |
| Sequence Caution | Sequence=AAB58382.1; Type=Miscellaneous discrepancy; Note=Many Frameshifts and conflicts.; Evidence= ; Sequence=CAE01470.2; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence= ; |
| Similarity | Contains 1 ATP-grasp domain. {ECO |
| Similarity | Contains 1 biotin carboxylation domain. |
| Similarity | Contains 1 biotinyl-binding domain. |
| Similarity | Contains 1 carboxyltransferase domain. |
| Subcellular Location | Mitochondrion . Nucleus . 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. |
| 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 |
Identical and Related Proteins
Unique RefSeq proteins for LMP006663 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 134142062 | RefSeq | NP_001084 | 2458 | acetyl-CoA carboxylase 2 precursor |
Identical Sequences to LMP006663 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:134142062 | GenBank | AAI72264.1 | 2458 | Acetyl-Coenzyme A carboxylase beta, partial [synthetic construct] |
| GI:134142062 | GenBank | AAI72569.1 | 2458 | Acetyl-Coenzyme A carboxylase beta [synthetic construct] |
| GI:134142062 | RefSeq | XP_005253933.1 | 2458 | PREDICTED: acetyl-CoA carboxylase 2 isoform X1 [Homo sapiens] |
| GI:134142062 | RefSeq | XP_006719428.1 | 2458 | PREDICTED: acetyl-CoA carboxylase 2 isoform X5 [Homo sapiens] |
| GI:134142062 | SwissProt | O00763.3 | 2458 | RecName: Full=Acetyl-CoA carboxylase 2; AltName: Full=ACC-beta; Includes: RecName: Full=Biotin carboxylase; Flags: Precursor [Homo sapiens] |
Related Sequences to LMP006663 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:134142062 | EMBL | CAE01471.3 | 2458 | Acetyl-CoA carboxylase 2 [Homo sapiens] |
| GI:134142062 | GenBank | EAW97853.1 | 2458 | acetyl-Coenzyme A carboxylase beta, isoform CRA_b [Homo sapiens] |
| GI:134142062 | GenBank | AGB64442.1 | 2458 | Sequence 2 from patent US 8288405 |
| GI:134142062 | GenBank | AGM84073.1 | 2458 | Sequence 18 from patent US 8389207 |
| GI:134142062 | GenBank | AGU38008.1 | 2458 | Sequence 2 from patent US 8507681 |
| GI:134142062 | GenBank | AHD75421.1 | 2458 | Sequence 17184 from patent US 8586006 |