GenomeNet

Database: UniProt
Entry: O00763
LinkDB: O00763
Original site: O00763 
ID   ACACB_HUMAN             Reviewed;        2458 AA.
AC   O00763; A6NK36; Q16852; Q1HEC1; Q6KE87; Q6KE89; Q6TY48;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   05-OCT-2010, sequence version 3.
DT   29-OCT-2014, entry version 147.
DE   RecName: Full=Acetyl-CoA carboxylase 2;
DE            EC=6.4.1.2 {ECO:0000269|PubMed:16854592, ECO:0000269|PubMed:20952656};
DE   AltName: Full=ACC-beta;
DE   Includes:
DE     RecName: Full=Biotin carboxylase;
DE              EC=6.3.4.14;
DE   Flags: Precursor;
GN   Name=ACACB; Synonyms=ACC2, ACCB;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=9099716; DOI=10.1074/jbc.272.16.10669;
RA   Abu-Elheiga L., Almarza-Ortega D.B., Baldini A., Wakil S.J.;
RT   "Human acetyl-CoA carboxylase 2. Molecular cloning, characterization,
RT   chromosomal mapping, and evidence for two isoforms.";
RL   J. Biol. Chem. 272:10669-10677(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), COFACTOR, BIOPHYSICOCHEMICAL
RP   PROPERTIES, CATALYTIC ACTIVITY, ENZYME REGULATION, AND VARIANT
RP   ILE-2141.
RX   PubMed=16854592; DOI=10.1016/j.pep.2006.06.005;
RA   Cheng D., Chu C.-H., Chen L., Feder J.N., Mintier G.A., Wu Y.,
RA   Cook J.W., Harpel M.R., Locke G.A., An Y., Tamura J.K.;
RT   "Expression, purification, and characterization of human and rat
RT   acetyl coenzyme A carboxylase (ACC) isozymes.";
RL   Protein Expr. Purif. 51:11-21(2007).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ILE-2141.
RC   TISSUE=Heart;
RA   Peng X.R., Lindgren K., Corneliussen B.;
RT   "Corrected sequence for human acetyl-CoA carboxylase 2 obtained by
RT   alignment to human genomic DNA and PCR cloning from human skeletal
RT   muscle and heart cDNA.";
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Heart;
RA   Mao J., Wakil S.J.;
RT   "Alternative splicing in the human acetyl-CoA carboxylase 2 (ACC2)
RT   gene.";
RL   Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA   Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA   Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA   Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA   Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA   Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA   Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA   Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA   Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA   Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA   Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA   Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA   Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA   Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA   Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA   Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA   Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA   Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA   Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA   Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA   Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA   Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA   Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA   Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA   Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA   Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA   Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA   Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA   Kucherlapati R., Weinstock G., Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1324-2109.
RC   TISSUE=Adipose tissue;
RX   PubMed=8670171;
RA   Widmer J., Fassihi K.S., Schlichter S.C., Wheeler K.S., Crute B.E.,
RA   King N., Nutile-Mcmenemy N., Noll W.W., Daniel S., Ha J., Kim K.-H.,
RA   Witters L.A.;
RT   "Identification of a second human acetyl-CoA carboxylase gene.";
RL   Biochem. J. 316:915-922(1996).
RN   [7]
RP   SUBCELLULAR LOCATION.
RX   PubMed=10677481; DOI=10.1073/pnas.97.4.1444;
RA   Abu-Elheiga L., Brinkley W.R., Zhong L., Chirala S.S.,
RA   Woldegiorgis G., Wakil S.J.;
RT   "The subcellular localization of acetyl-CoA carboxylase 2.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:1444-1449(2000).
RN   [8]
RP   PHOSPHORYLATION AT SER-222 BY AMPK.
RX   PubMed=12488245; DOI=10.1152/ajpendo.00436.2002;
RA   Wojtaszewski J.F., MacDonald C., Nielsen J.N., Hellsten Y.,
RA   Hardie D.G., Kemp B.E., Kiens B., Richter E.A.;
RT   "Regulation of 5'AMP-activated protein kinase activity and substrate
RT   utilization in exercising human skeletal muscle.";
RL   Am. J. Physiol. 284:E813-E822(2003).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [10]
RP   BIOPHYSICOCHEMICAL PROPERTIES, ALTERNATIVE SPLICING (ISOFORM 3), AND
RP   TISSUE SPECIFICITY.
RX   PubMed=19190759; DOI=10.1371/journal.pone.0004369;
RA   Castle J.C., Hara Y., Raymond C.K., Garrett-Engele P., Ohwaki K.,
RA   Kan Z., Kusunoki J., Johnson J.M.;
RT   "ACC2 is expressed at high levels in human white adipose and has an
RT   isoform with a novel N-terminus.";
RL   PLoS ONE 4:E4369-E4369(2009).
RN   [11]
RP   CATALYTIC ACTIVITY, SUBUNIT, ENZYME REGULATION, AND INTERACTION WITH
RP   MID1IP1.
RX   PubMed=20952656; DOI=10.1073/pnas.1012736107;
RA   Colbert C.L., Kim C.W., Moon Y.A., Henry L., Palnitkar M.,
RA   McKean W.B., Fitzgerald K., Deisenhofer J., Horton J.D., Kwon H.J.;
RT   "Crystal structure of Spot 14, a modulator of fatty acid synthesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:18820-18825(2010).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 217-775.
RX   PubMed=17876819; DOI=10.1002/prot.21611;
RA   Cho Y.S., Lee J.I., Shin D., Kim H.T., Cheon Y.H., Seo C.I., Kim Y.E.,
RA   Hyun Y.L., Lee Y.S., Sugiyama K., Park S.Y., Ro S., Cho J.M.,
RA   Lee T.G., Heo Y.S.;
RT   "Crystal structure of the biotin carboxylase domain of human acetyl-
RT   CoA carboxylase 2.";
RL   Proteins 70:268-272(2008).
RN   [13]
RP   STRUCTURE BY NMR OF 885-971.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of RSGI RUH-053, an apo-biotin carboxy carrier
RT   protein from human transcarboxylase.";
RL   Submitted (OCT-2006) to the PDB data bank.
RN   [14]
RP   VARIANT [LARGE SCALE ANALYSIS] LEU-193.
RX   PubMed=18772397; DOI=10.1126/science.1164368;
RA   Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P.,
RA   Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B.,
RA   Lin M.T., Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T.,
RA   Nikolsky Y., Hartigan J., Smith D.R., Hidalgo M., Leach S.D.,
RA   Klein A.P., Jaffee E.M., Goggins M., Maitra A., Iacobuzio-Donahue C.,
RA   Eshleman J.R., Kern S.E., Hruban R.H., Karchin R., Papadopoulos N.,
RA   Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W.;
RT   "Core signaling pathways in human pancreatic cancers revealed by
RT   global genomic analyses.";
RL   Science 321:1801-1806(2008).
CC   -!- FUNCTION: Catalyzes the ATP-dependent carboxylation of acetyl-CoA
CC       to malonyl-CoA. Carries out three functions: biotin carboxyl
CC       carrier protein, biotin carboxylase and carboxyltransferase.
CC       Involved in inhibition of fatty acid and glucose oxidation and
CC       enhancement of fat storage (By similarity). May play a role in
CC       regulation of mitochondrial fatty acid oxidation through malonyl-
CC       CoA-dependent inhibition of carnitine palmitoyltransferase 1 (By
CC       similarity). {ECO:0000250|UniProtKB:E9Q4Z2,
CC       ECO:0000269|PubMed:20952656}.
CC   -!- CATALYTIC ACTIVITY: ATP + acetyl-CoA + HCO(3)(-) = ADP + phosphate
CC       + malonyl-CoA. {ECO:0000269|PubMed:16854592,
CC       ECO:0000269|PubMed:20952656}.
CC   -!- CATALYTIC ACTIVITY: ATP + biotin-[carboxyl-carrier-protein] +
CC       CO(2) = ADP + phosphate + carboxy-biotin-[carboxyl-carrier-
CC       protein]. {ECO:0000250}.
CC   -!- COFACTOR: Biotin. {ECO:0000250}.
CC   -!- COFACTOR: Binds 2 manganese ions per subunit. {ECO:0000250}.
CC   -!- ENZYME REGULATION: Activity is increased by oligomerization.
CC       Activated by citrate. Citrate and MID1IP1 promote oligomerization.
CC       Inhibited by malonyl-CoA. {ECO:0000269|PubMed:16854592,
CC       ECO:0000269|PubMed:20952656}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=120 uM for ATP {ECO:0000269|PubMed:16854592};
CC         KM=110 uM for ATP (isoform 2) {ECO:0000269|PubMed:19190759};
CC         KM=58 uM for acetyl-CoA {ECO:0000269|PubMed:16854592};
CC         KM=94 uM for acetyl-CoA (isoform 3)
CC         {ECO:0000269|PubMed:19190759};
CC         KM=6.5 mM for NaHCO3 (isoform 3) {ECO:0000269|PubMed:19190759};
CC         KM=3.0 mM for NaHCO(3) {ECO:0000269|PubMed:16854592};
CC   -!- PATHWAY: Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA
CC       from acetyl-CoA: step 1/1.
CC   -!- SUBUNIT: Monomer, homodimer, and homotetramer. Can form
CC       filamentous polymers. Interacts with MID1IP1; interaction with
CC       MID1IP1 promotes oligomerization and increases its activity.
CC       {ECO:0000269|PubMed:20952656}.
CC   -!- INTERACTION:
CC       P50747:HLCS; NbExp=4; IntAct=EBI-2211739, EBI-3915568;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10677481}.
CC       Nucleus {ECO:0000269|PubMed:10677481}. Endomembrane system.
CC       Note=May associate with membranes.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=Long;
CC         IsoId=O00763-1; Sequence=Displayed;
CC       Name=2; Synonyms=Short;
CC         IsoId=O00763-2; Sequence=VSP_000547;
CC       Name=3 {ECO:0000305}; Synonyms=ACC2.v2
CC       {ECO:0000303|PubMed:19190759};
CC         IsoId=O00763-3; Sequence=VSP_057081, VSP_057082;
CC   -!- TISSUE SPECIFICITY: Widely expressed with highest levels in heart,
CC       skeletal muscle, liver, adipose tissue, mammary gland, adrenal
CC       gland and colon (PubMed:9099716). Isoform 3 is expressed in
CC       skeletal muscle, adipose tissue and liver (at protein level)
CC       (PubMed:19190759). Isoform 3 is detected at high levels in adipose
CC       tissue with lower levels in heart, liver, skeletal muscle and
CC       testis (PubMed:19190759). {ECO:0000269|PubMed:19190759,
CC       ECO:0000269|PubMed:9099716}.
CC   -!- PTM: Phosphorylated by AMPK, leading to inactivation of the
CC       enzyme. Required for the maintenance of skeletal muscle lipid and
CC       glucose homeostasis (By similarity).
CC       {ECO:0000250|UniProtKB:E9Q4Z2, ECO:0000269|PubMed:12488245}.
CC   -!- BIOTECHNOLOGY: Inhibition of ACACB may prevent lipid-induced
CC       insulin resistance and type 2 diabetes, making the enzyme a
CC       potential pharmaceutical target for treatment of obesity and type
CC       2 diabetes. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 ATP-grasp domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00409}.
CC   -!- SIMILARITY: Contains 1 biotin carboxylation domain. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 biotinyl-binding domain. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 carboxyltransferase domain. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB58382.1; Type=Miscellaneous discrepancy; Note=Many Frameshifts and conflicts.; Evidence={ECO:0000305};
CC       Sequence=CAE01470.2; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
DR   EMBL; U89344; AAB58382.1; ALT_SEQ; mRNA.
DR   EMBL; DQ493870; ABF48723.1; -; mRNA.
DR   EMBL; AJ575431; CAE01470.2; ALT_SEQ; mRNA.
DR   EMBL; AJ575592; CAE01471.3; -; mRNA.
DR   EMBL; AY382667; AAR37018.1; -; mRNA.
DR   EMBL; AC007637; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; U34591; AAC50571.1; -; mRNA.
DR   CCDS; CCDS31898.1; -. [O00763-1]
DR   PIR; S71091; S71091.
DR   RefSeq; NP_001084.3; NM_001093.3. [O00763-1]
DR   RefSeq; XP_005253933.1; XM_005253876.2. [O00763-1]
DR   RefSeq; XP_006719428.1; XM_006719365.1. [O00763-1]
DR   UniGene; Hs.234898; -.
DR   PDB; 2DN8; NMR; -; A=885-971.
DR   PDB; 2HJW; X-ray; 2.50 A; A=217-775.
DR   PDB; 2KCC; NMR; -; A=891-965.
DR   PDB; 3FF6; X-ray; 3.19 A; A/B/C/D=1693-2450.
DR   PDB; 3GID; X-ray; 2.30 A; A/B=238-760.
DR   PDB; 3GLK; X-ray; 2.10 A; A=238-760.
DR   PDB; 3JRW; X-ray; 2.60 A; A=217-775.
DR   PDB; 3JRX; X-ray; 2.50 A; A=217-775.
DR   PDB; 3TDC; X-ray; 2.41 A; A=1690-2445.
DR   PDB; 4HQ6; X-ray; 2.70 A; A=217-776.
DR   PDBsum; 2DN8; -.
DR   PDBsum; 2HJW; -.
DR   PDBsum; 2KCC; -.
DR   PDBsum; 3FF6; -.
DR   PDBsum; 3GID; -.
DR   PDBsum; 3GLK; -.
DR   PDBsum; 3JRW; -.
DR   PDBsum; 3JRX; -.
DR   PDBsum; 3TDC; -.
DR   PDBsum; 4HQ6; -.
DR   ProteinModelPortal; O00763; -.
DR   SMR; O00763; 237-758, 891-960, 1695-2449.
DR   BioGrid; 106550; 5.
DR   DIP; DIP-51617N; -.
DR   IntAct; O00763; 5.
DR   MINT; MINT-6800190; -.
DR   STRING; 9606.ENSP00000367079; -.
DR   BindingDB; O00763; -.
DR   ChEMBL; CHEMBL4829; -.
DR   DrugBank; DB00173; Adenine.
DR   DrugBank; DB00121; Biotin.
DR   GuidetoPHARMACOLOGY; 1264; -.
DR   PhosphoSite; O00763; -.
DR   MaxQB; O00763; -.
DR   PaxDb; O00763; -.
DR   PRIDE; O00763; -.
DR   DNASU; 32; -.
DR   Ensembl; ENST00000338432; ENSP00000341044; ENSG00000076555. [O00763-1]
DR   Ensembl; ENST00000377848; ENSP00000367079; ENSG00000076555. [O00763-1]
DR   GeneID; 32; -.
DR   KEGG; hsa:32; -.
DR   UCSC; uc001tob.3; human. [O00763-1]
DR   CTD; 32; -.
DR   GeneCards; GC12P109577; -.
DR   H-InvDB; HIX0036741; -.
DR   HGNC; HGNC:85; ACACB.
DR   HPA; HPA006554; -.
DR   MIM; 601557; gene.
DR   neXtProt; NX_O00763; -.
DR   PharmGKB; PA24422; -.
DR   eggNOG; COG0511; -.
DR   GeneTree; ENSGT00550000074703; -.
DR   HOVERGEN; HBG005371; -.
DR   InParanoid; O00763; -.
DR   KO; K11262; -.
DR   OMA; WRLRVAQ; -.
DR   OrthoDB; EOG7HXCPW; -.
DR   PhylomeDB; O00763; -.
DR   TreeFam; TF300061; -.
DR   BioCyc; MetaCyc:HS01211-MONOMER; -.
DR   BRENDA; 6.4.1.2; 2681.
DR   Reactome; REACT_11082; Import of palmitoyl-CoA into the mitochondrial matrix.
DR   Reactome; REACT_11153; Biotin transport and metabolism.
DR   Reactome; REACT_147904; Activation of gene expression by SREBF (SREBP).
DR   Reactome; REACT_169312; Defective HLCS causes multiple carboxylase deficiency.
DR   Reactome; REACT_2122; ChREBP activates metabolic gene expression.
DR   SABIO-RK; O00763; -.
DR   UniPathway; UPA00655; UER00711.
DR   EvolutionaryTrace; O00763; -.
DR   GeneWiki; ACACB; -.
DR   GenomeRNAi; 32; -.
DR   NextBio; 123; -.
DR   PRO; PR:O00763; -.
DR   Bgee; O00763; -.
DR   CleanEx; HS_ACACB; -.
DR   ExpressionAtlas; O00763; baseline and differential.
DR   Genevestigator; O00763; -.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0003989; F:acetyl-CoA carboxylase activity; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0009374; F:biotin binding; IEA:Ensembl.
DR   GO; GO:0004075; F:biotin carboxylase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006084; P:acetyl-CoA metabolic process; IDA:UniProtKB.
DR   GO; GO:0006768; P:biotin metabolic process; TAS:Reactome.
DR   GO; GO:0006853; P:carnitine shuttle; TAS:Reactome.
DR   GO; GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
DR   GO; GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:2001295; P:malonyl-CoA biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0031325; P:positive regulation of cellular metabolic process; TAS:Reactome.
DR   GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR   GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR   GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR   GO; GO:0006766; P:vitamin metabolic process; TAS:Reactome.
DR   GO; GO:0006767; P:water-soluble vitamin metabolic process; TAS:Reactome.
DR   Gene3D; 3.30.1490.20; -; 1.
DR   Gene3D; 3.30.470.20; -; 1.
DR   Gene3D; 3.40.50.20; -; 1.
DR   Gene3D; 3.90.226.10; -; 3.
DR   InterPro; IPR013537; AcCoA_COase_cen.
DR   InterPro; IPR011761; ATP-grasp.
DR   InterPro; IPR013815; ATP_grasp_subdomain_1.
DR   InterPro; IPR013816; ATP_grasp_subdomain_2.
DR   InterPro; IPR011764; Biotin_carboxylation_dom.
DR   InterPro; IPR005482; Biotin_COase_C.
DR   InterPro; IPR000089; Biotin_lipoyl.
DR   InterPro; IPR005481; CarbamoylP_synth_lsu_N.
DR   InterPro; IPR000022; Carboxyl_trans.
DR   InterPro; IPR005479; CbamoylP_synth_lsu-like_ATP-bd.
DR   InterPro; IPR029045; ClpP/crotonase-like_dom.
DR   InterPro; IPR011763; COA_CT_C.
DR   InterPro; IPR011762; COA_CT_N.
DR   InterPro; IPR016185; PreATP-grasp_dom.
DR   InterPro; IPR011054; Rudment_hybrid_motif.
DR   InterPro; IPR011053; Single_hybrid_motif.
DR   Pfam; PF08326; ACC_central; 1.
DR   Pfam; PF02785; Biotin_carb_C; 1.
DR   Pfam; PF00364; Biotin_lipoyl; 1.
DR   Pfam; PF01039; Carboxyl_trans; 1.
DR   Pfam; PF00289; CPSase_L_chain; 1.
DR   Pfam; PF02786; CPSase_L_D2; 1.
DR   SMART; SM00878; Biotin_carb_C; 1.
DR   SUPFAM; SSF51230; SSF51230; 1.
DR   SUPFAM; SSF51246; SSF51246; 1.
DR   SUPFAM; SSF52096; SSF52096; 2.
DR   SUPFAM; SSF52440; SSF52440; 1.
DR   PROSITE; PS50975; ATP_GRASP; 1.
DR   PROSITE; PS50979; BC; 1.
DR   PROSITE; PS50968; BIOTINYL_LIPOYL; 1.
DR   PROSITE; PS50989; COA_CT_CTER; 1.
DR   PROSITE; PS50980; COA_CT_NTER; 1.
DR   PROSITE; PS00866; CPSASE_1; 1.
DR   PROSITE; PS00867; CPSASE_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding;
KW   Biotin; Complete proteome; Fatty acid biosynthesis;
KW   Fatty acid metabolism; Ligase; Lipid biosynthesis; Lipid metabolism;
KW   Manganese; Membrane; Metal-binding; Mitochondrion;
KW   Multifunctional enzyme; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Polymorphism; Reference proteome; Transit peptide.
FT   TRANSIT       1      ?       Mitochondrion.
FT                                {ECO:0000250|UniProtKB:E9Q4Z2}.
FT   CHAIN         ?   2458       Acetyl-CoA carboxylase 2. {ECO:0000305}.
FT                                /FTId=PRO_0000146767.
FT   DOMAIN      259    761       Biotin carboxylation.
FT   DOMAIN      414    609       ATP-grasp. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00409}.
FT   DOMAIN      895    961       Biotinyl-binding.
FT   DOMAIN     1809   2305       Carboxyltransferase.
FT   NP_BIND     458    463       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00409}.
FT   ACT_SITE    584    584       {ECO:0000250}.
FT   METAL       567    567       Manganese 1. {ECO:0000250}.
FT   METAL       580    580       Manganese 1. {ECO:0000250}.
FT   METAL       580    580       Manganese 2. {ECO:0000250}.
FT   METAL       582    582       Manganese 2. {ECO:0000250}.
FT   BINDING    1934   1934       Coenzyme A. {ECO:0000250}.
FT   BINDING    2238   2238       Coenzyme A. {ECO:0000250}.
FT   BINDING    2240   2240       Coenzyme A. {ECO:0000250}.
FT   MOD_RES     222    222       Phosphoserine; by AMPK.
FT                                {ECO:0000269|PubMed:12488245}.
FT   MOD_RES     929    929       N6-biotinyllysine. {ECO:0000250}.
FT   VAR_SEQ       1    202       Missing (in isoform 3).
FT                                {ECO:0000269|PubMed:19190759}.
FT                                /FTId=VSP_057081.
FT   VAR_SEQ     203    218       AYLTTGEAETRVPTMR -> MSPAKCKICFPDREVK (in
FT                                isoform 3).
FT                                {ECO:0000269|PubMed:19190759}.
FT                                /FTId=VSP_057082.
FT   VAR_SEQ    1118   1187       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:9099716}.
FT                                /FTId=VSP_000547.
FT   VARIANT     193    193       R -> L (in a pancreatic ductal
FT                                adenocarcinoma sample; somatic mutation).
FT                                {ECO:0000269|PubMed:18772397}.
FT                                /FTId=VAR_062667.
FT   VARIANT     552    552       I -> V (in dbSNP:rs16940029).
FT                                /FTId=VAR_031255.
FT   VARIANT     651    651       A -> T (in dbSNP:rs2300455).
FT                                /FTId=VAR_031256.
FT   VARIANT    2141   2141       V -> I (in dbSNP:rs2075260).
FT                                {ECO:0000269|PubMed:16854592,
FT                                ECO:0000269|Ref.3}.
FT                                /FTId=VAR_031257.
FT   CONFLICT      9      9       C -> R (in Ref. 2; ABF48723).
FT                                {ECO:0000305}.
FT   CONFLICT    120    120       T -> I (in Ref. 4; AAR37018).
FT                                {ECO:0000305}.
FT   CONFLICT    422    422       I -> T (in Ref. 4; AAR37018).
FT                                {ECO:0000305}.
FT   CONFLICT   1340   1340       S -> N (in Ref. 6; AAC50571).
FT                                {ECO:0000305}.
FT   CONFLICT   1383   1383       D -> G (in Ref. 6; AAC50571).
FT                                {ECO:0000305}.
FT   CONFLICT   1425   1425       V -> M (in Ref. 6; AAC50571).
FT                                {ECO:0000305}.
FT   CONFLICT   1819   1821       AEG -> PEA (in Ref. 6; AAC50571).
FT                                {ECO:0000305}.
FT   CONFLICT   1892   1893       MI -> IM (in Ref. 6; AAC50571).
FT                                {ECO:0000305}.
FT   HELIX       247    253       {ECO:0000244|PDB:3GLK}.
FT   STRAND      262    265       {ECO:0000244|PDB:3GLK}.
FT   HELIX       269    287       {ECO:0000244|PDB:3GLK}.
FT   STRAND      292    299       {ECO:0000244|PDB:3GLK}.
FT   HELIX       301    305       {ECO:0000244|PDB:3GLK}.
FT   HELIX       309    313       {ECO:0000244|PDB:3GLK}.
FT   STRAND      314    319       {ECO:0000244|PDB:3GLK}.
FT   HELIX       325    327       {ECO:0000244|PDB:3GLK}.
FT   TURN        328    330       {ECO:0000244|PDB:3GLK}.
FT   HELIX       332    341       {ECO:0000244|PDB:3GLK}.
FT   STRAND      345    348       {ECO:0000244|PDB:3GLK}.
FT   HELIX       353    356       {ECO:0000244|PDB:3GLK}.
FT   HELIX       359    366       {ECO:0000244|PDB:3GLK}.
FT   STRAND      370    373       {ECO:0000244|PDB:3GLK}.
FT   HELIX       376    379       {ECO:0000244|PDB:3GLK}.
FT   HELIX       385    394       {ECO:0000244|PDB:3GLK}.
FT   TURN        403    406       {ECO:0000244|PDB:3GLK}.
FT   HELIX       426    431       {ECO:0000244|PDB:3GLK}.
FT   HELIX       437    447       {ECO:0000244|PDB:3GLK}.
FT   STRAND      449    455       {ECO:0000244|PDB:3GLK}.
FT   STRAND      464    467       {ECO:0000244|PDB:3GLK}.
FT   TURN        470    472       {ECO:0000244|PDB:3GLK}.
FT   HELIX       473    483       {ECO:0000244|PDB:3GLK}.
FT   STRAND      489    493       {ECO:0000244|PDB:3GLK}.
FT   STRAND      496    507       {ECO:0000244|PDB:3GLK}.
FT   STRAND      509    511       {ECO:0000244|PDB:3JRX}.
FT   STRAND      513    523       {ECO:0000244|PDB:3GLK}.
FT   STRAND      524    527       {ECO:0000244|PDB:4HQ6}.
FT   STRAND      530    535       {ECO:0000244|PDB:3GLK}.
FT   HELIX       541    558       {ECO:0000244|PDB:3GLK}.
FT   STRAND      562    571       {ECO:0000244|PDB:3GLK}.
FT   STRAND      572    574       {ECO:0000244|PDB:2HJW}.
FT   STRAND      576    582       {ECO:0000244|PDB:3GLK}.
FT   HELIX       589    596       {ECO:0000244|PDB:3GLK}.
FT   HELIX       600    608       {ECO:0000244|PDB:3GLK}.
FT   HELIX       613    615       {ECO:0000244|PDB:3GLK}.
FT   HELIX       617    622       {ECO:0000244|PDB:3GLK}.
FT   STRAND      635    637       {ECO:0000244|PDB:2HJW}.
FT   STRAND      646    653       {ECO:0000244|PDB:3GLK}.
FT   STRAND      669    671       {ECO:0000244|PDB:3GLK}.
FT   STRAND      679    685       {ECO:0000244|PDB:3GLK}.
FT   STRAND      700    709       {ECO:0000244|PDB:3GLK}.
FT   HELIX       710    724       {ECO:0000244|PDB:3GLK}.
FT   HELIX       728    730       {ECO:0000244|PDB:2HJW}.
FT   HELIX       732    742       {ECO:0000244|PDB:3GLK}.
FT   HELIX       744    748       {ECO:0000244|PDB:3GLK}.
FT   HELIX       754    756       {ECO:0000244|PDB:2HJW}.
FT   STRAND      896    898       {ECO:0000244|PDB:2DN8}.
FT   STRAND      900    902       {ECO:0000244|PDB:2KCC}.
FT   STRAND      903    910       {ECO:0000244|PDB:2DN8}.
FT   STRAND      914    916       {ECO:0000244|PDB:2DN8}.
FT   STRAND      921    927       {ECO:0000244|PDB:2DN8}.
FT   STRAND      930    935       {ECO:0000244|PDB:2DN8}.
FT   STRAND      937    944       {ECO:0000244|PDB:2DN8}.
FT   STRAND      957    961       {ECO:0000244|PDB:2DN8}.
FT   TURN       1698   1700       {ECO:0000244|PDB:3FF6}.
FT   HELIX      1703   1711       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1717   1719       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1720   1732       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1742   1750       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1756   1759       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1767   1777       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1786   1793       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1798   1800       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1804   1820       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1824   1828       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1839   1842       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1846   1850       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1855   1857       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1859   1864       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1866   1872       {ECO:0000244|PDB:3TDC}.
FT   TURN       1873   1876       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1878   1885       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1888   1896       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1899   1901       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1905   1924       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1927   1931       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1933   1936       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1938   1946       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1948   1952       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1956   1960       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1962   1969       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1977   1981       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1983   1986       {ECO:0000244|PDB:3TDC}.
FT   TURN       1987   1990       {ECO:0000244|PDB:3TDC}.
FT   STRAND     1993   1998       {ECO:0000244|PDB:3TDC}.
FT   HELIX      1999   2010       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2045   2050       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2055   2057       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2072   2075       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2082   2089       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2092   2099       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2104   2108       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2120   2124       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2131   2147       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2151   2154       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2164   2168       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2171   2183       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2189   2193       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2198   2200       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2201   2205       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2209   2211       {ECO:0000244|PDB:3TDC}.
FT   TURN       2213   2215       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2216   2221       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2225   2229       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2231   2238       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2241   2251       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2253   2261       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2269   2299       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2300   2302       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2304   2309       {ECO:0000244|PDB:3TDC}.
FT   STRAND     2312   2317       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2319   2321       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2322   2344       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2345   2348       {ECO:0000244|PDB:3FF6}.
FT   HELIX      2352   2365       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2369   2376       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2378   2388       {ECO:0000244|PDB:3TDC}.
FT   HELIX      2404   2420       {ECO:0000244|PDB:3TDC}.
FT   TURN       2423   2425       {ECO:0000244|PDB:3FF6}.
FT   HELIX      2426   2435       {ECO:0000244|PDB:3FF6}.
FT   HELIX      2439   2448       {ECO:0000244|PDB:3FF6}.
SQ   SEQUENCE   2458 AA;  276541 MW;  ED12674A1A8A0706 CRC64;
     MVLLLCLSCL IFSCLTFSWL KIWGKMTDSK PITKSKSEAN LIPSQEPFPA SDNSGETPQR
     NGEGHTLPKT PSQAEPASHK GPKDAGRRRN SLPPSHQKPP RNPLSSSDAA PSPELQANGT
     GTQGLEATDT NGLSSSARPQ GQQAGSPSKE DKKQANIKRQ LMTNFILGSF DDYSSDEDSV
     AGSSRESTRK GSRASLGALS LEAYLTTGEA ETRVPTMRPS MSGLHLVKRG REHKKLDLHR
     DFTVASPAEF VTRFGGDRVI EKVLIANNGI AAVKCMRSIR RWAYEMFRNE RAIRFVVMVT
     PEDLKANAEY IKMADHYVPV PGGPNNNNYA NVELIVDIAK RIPVQAVWAG WGHASENPKL
     PELLCKNGVA FLGPPSEAMW ALGDKIASTV VAQTLQVPTL PWSGSGLTVE WTEDDLQQGK
     RISVPEDVYD KGCVKDVDEG LEAAERIGFP LMIKASEGGG GKGIRKAESA EDFPILFRQV
     QSEIPGSPIF LMKLAQHARH LEVQILADQY GNAVSLFGRD CSIQRRHQKI VEEAPATIAP
     LAIFEFMEQC AIRLAKTVGY VSAGTVEYLY SQDGSFHFLE LNPRLQVEHP CTEMIADVNL
     PAAQLQIAMG VPLHRLKDIR LLYGESPWGV TPISFETPSN PPLARGHVIA ARITSENPDE
     GFKPSSGTVQ ELNFRSSKNV WGYFSVAATG GLHEFADSQF GHCFSWGENR EEAISNMVVA
     LKELSIRGDF RTTVEYLINL LETESFQNND IDTGWLDYLI AEKVQAEKPD IMLGVVCGAL
     NVADAMFRTC MTDFLHSLER GQVLPADSLL NLVDVELIYG GVKYILKVAR QSLTMFVLIM
     NGCHIEIDAH RLNDGGLLLS YNGNSYTTYM KEEVDSYRIT IGNKTCVFEK ENDPTVLRSP
     SAGKLTQYTV EDGGHVEAGS SYAEMEVMKM IMTLNVQERG RVKYIKRPGA VLEAGCVVAR
     LELDDPSKVH PAEPFTGELP AQQTLPILGE KLHQVFHSVL ENLTNVMSGF CLPEPVFSIK
     LKEWVQKLMM TLRHPSLPLL ELQEIMTSVA GRIPAPVEKS VRRVMAQYAS NITSVLCQFP
     SQQIATILDC HAATLQRKAD REVFFINTQS IVQLVQRYRS GIRGYMKTVV LDLLRRYLRV
     EHHFQQAHYD KCVINLREQF KPDMSQVLDC IFSHAQVAKK NQLVIMLIDE LCGPDPSLSD
     ELISILNELT QLSKSEHCKV ALRARQILIA SHLPSYELRH NQVESIFLSA IDMYGHQFCP
     ENLKKLILSE TTIFDVLPTF FYHANKVVCM ASLEVYVRRG YIAYELNSLQ HRQLPDGTCV
     VEFQFMLPSS HPNRMTVPIS ITNPDLLRHS TELFMDSGFS PLCQRMGAMV AFRRFEDFTR
     NFDEVISCFA NVPKDTPLFS EARTSLYSED DCKSLREEPI HILNVSIQCA DHLEDEALVP
     ILRTFVQSKK NILVDYGLRR ITFLIAQEKE FPKFFTFRAR DEFAEDRIYR HLEPALAFQL
     ELNRMRNFDL TAVPCANHKM HLYLGAAKVK EGVEVTDHRF FIRAIIRHSD LITKEASFEY
     LQNEGERLLL EAMDELEVAF NNTSVRTDCN HIFLNFVPTV IMDPFKIEES VRYMVMRYGS
     RLWKLRVLQA EVKINIRQTT TGSAVPIRLF ITNESGYYLD ISLYKEVTDS RSGNIMFHSF
     GNKQGPQHGM LINTPYVTKD LLQAKRFQAQ TLGTTYIYDF PEMFRQALFK LWGSPDKYPK
     DILTYTELVL DSQGQLVEMN RLPGGNEVGM VAFKMRFKTQ EYPEGRDVIV IGNDITFRIG
     SFGPGEDLLY LRASEMARAE GIPKIYVAAN SGARIGMAEE IKHMFHVAWV DPEDPHKGFK
     YLYLTPQDYT RISSLNSVHC KHIEEGGESR YMITDIIGKD DGLGVENLRG SGMIAGESSL
     AYEEIVTISL VTCRAIGIGA YLVRLGQRVI QVENSHIILT GASALNKVLG REVYTSNNQL
     GGVQIMHYNG VSHITVPDDF EGVYTILEWL SYMPKDNHSP VPIITPTDPI DREIEFLPSR
     APYDPRWMLA GRPHPTLKGT WQSGFFDHGS FKEIMAPWAQ TVVTGRARLG GIPVGVIAVE
     TRTVEVAVPA DPANLDSEAK IIQQAGQVWF PDSAYKTAQA VKDFNREKLP LMIFANWRGF
     SGGMKDMYDQ VLKFGAYIVD GLRQYKQPIL IYIPPYAELR GGSWVVIDAT INPLCIEMYA
     DKESRGGVLE PEGTVEIKFR KKDLIKSMRR IDPAYKKLME QLGEPDLSDK DRKDLEGRLK
     AREDLLLPIY HQVAVQFADF HDTPGRMLEK GVISDILEWK TARTFLYWRL RRLLLEDQVK
     QEILQASGEL SHVHIQSMLR RWFVETEGAV KAYLWDNNQV VVQWLEQHWQ AGDGPRSTIR
     ENITYLKHDS VLKTIRGLVE ENPEVAVDCV IYLSQHISPA ERAQVVHLLS TMDSPAST
//
DBGET integrated database retrieval system