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 27-MAR-2024, entry version 216. DE RecName: Full=Acetyl-CoA carboxylase 2 {ECO:0000305}; DE EC=6.4.1.2 {ECO:0000269|PubMed:16854592, ECO:0000269|PubMed:19236960, ECO:0000269|PubMed:19900410, ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:26976583}; DE AltName: Full=ACC-beta; DE Flags: Precursor; GN Name=ACACB {ECO:0000312|HGNC:HGNC:85}; Synonyms=ACC2, ACCB; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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), FUNCTION, COFACTOR, RP BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND RP VARIANT 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., Cook J.W., RA Harpel M.R., Locke G.A., An Y., Tamura J.K.; RT "Expression, purification, and characterization of human and rat acetyl RT 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 muscle RT 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) 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., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., 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., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., 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., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA 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; DOI=10.1042/bj3160915; 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., Woldegiorgis G., RA 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, AND ACTIVITY REGULATION. RX PubMed=12488245; DOI=10.1152/ajpendo.00436.2002; RA Wojtaszewski J.F., MacDonald C., Nielsen J.N., Hellsten Y., Hardie D.G., RA 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, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=19236960; DOI=10.1016/j.bbapap.2009.02.004; RA Kaushik V.K., Kavana M., Volz J.M., Weldon S.C., Hanrahan S., Xu J., RA Caplan S.L., Hubbard B.K.; RT "Characterization of recombinant human acetyl-CoA carboxylase-2 steady- RT state kinetics."; RL Biochim. Biophys. Acta 1794:961-967(2009). RN [11] RP BIOPHYSICOCHEMICAL PROPERTIES, ALTERNATIVE SPLICING (ISOFORM 3), AND TISSUE RP SPECIFICITY. RX PubMed=19190759; DOI=10.1371/journal.pone.0004369; RA Castle J.C., Hara Y., Raymond C.K., Garrett-Engele P., Ohwaki K., Kan Z., RA Kusunoki J., Johnson J.M.; RT "ACC2 is expressed at high levels in human white adipose and has an isoform RT with a novel N-terminus."; RL PLoS ONE 4:E4369-E4369(2009). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND INTERACTION RP WITH MID1IP1. RX PubMed=20457939; DOI=10.1073/pnas.1001292107; RA Kim C.W., Moon Y.A., Park S.W., Cheng D., Kwon H.J., Horton J.D.; RT "Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 RT provides a tertiary level of regulation of fatty acid synthesis."; RL Proc. Natl. Acad. Sci. U.S.A. 107:9626-9631(2010). RN [13] RP CATALYTIC ACTIVITY, SUBUNIT, ACTIVITY 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., McKean W.B., RA 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35; THR-70; SER-91; SER-95; RP SER-200; SER-469 AND THR-1342, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [15] 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., Lee T.G., RA Heo Y.S.; RT "Crystal structure of the biotin carboxylase domain of human acetyl-CoA RT carboxylase 2."; RL Proteins 70:268-272(2008). RN [16] 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 protein RT from human transcarboxylase."; RL Submitted (OCT-2006) to the PDB data bank. RN [17] RP STRUCTURE BY NMR OF 891-965, BIOTINYLATION AT LYS-929, COFACTOR, AND RP DOMAIN. RX PubMed=18247344; DOI=10.1002/prot.21952; RA Lee C.K., Cheong H.K., Ryu K.S., Lee J.I., Lee W., Jeon Y.H., Cheong C.; RT "Biotinoyl domain of human acetyl-CoA carboxylase: Structural insights into RT the carboxyl transfer mechanism."; RL Proteins 72:613-624(2008). RN [18] RP X-RAY CRYSTALLOGRAPHY (3.19 ANGSTROMS) OF 1693-2450 IN COMPLEX WITH RP INHIBITOR, AND DOMAIN. RX PubMed=19390150; DOI=10.1107/s0907444909008014; RA Madauss K.P., Burkhart W.A., Consler T.G., Cowan D.J., Gottschalk W.K., RA Miller A.B., Short S.A., Tran T.B., Williams S.P.; RT "The human ACC2 CT-domain C-terminus is required for full functionality and RT has a novel twist."; RL Acta Crystallogr. D 65:449-461(2009). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 217-775 IN COMPLEX WITH SORAPHEN RP A, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, SUBUNIT, RP PHOSPHORYLATION AT SER-222, AND MUTAGENESIS OF ARG-277 AND GLU-671. RX PubMed=19900410; DOI=10.1016/j.bbrc.2009.11.029; RA Cho Y.S., Lee J.I., Shin D., Kim H.T., Jung H.Y., Lee T.G., Kang L.W., RA Ahn Y.J., Cho H.S., Heo Y.S.; RT "Molecular mechanism for the regulation of human ACC2 through RT phosphorylation by AMPK."; RL Biochem. Biophys. Res. Commun. 391:187-192(2010). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 238-760 IN COMPLEX WITH RP INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=26976583; DOI=10.1073/pnas.1520686113; RA Harriman G., Greenwood J., Bhat S., Huang X., Wang R., Paul D., Tong L., RA Saha A.K., Westlin W.F., Kapeller R., Harwood H.J. Jr.; RT "Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, RT improves insulin sensitivity, and modulates dyslipidemia in rats."; RL Proc. Natl. Acad. Sci. U.S.A. 113:E1796-E1805(2016). RN [21] 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., Lin M.T., RA Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y., RA Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., RA Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., RA Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., RA Velculescu V.E., Kinzler K.W.; RT "Core signaling pathways in human pancreatic cancers revealed by global RT genomic analyses."; RL Science 321:1801-1806(2008). CC -!- FUNCTION: Mitochondrial enzyme that catalyzes the carboxylation of CC acetyl-CoA to malonyl-CoA and plays a central role in fatty acid CC metabolism (PubMed:16854592, PubMed:19236960, PubMed:20457939, CC PubMed:20952656, PubMed:19900410, PubMed:26976583). Catalyzes a 2 steps CC reaction starting with the ATP-dependent carboxylation of the biotin CC carried by the biotin carboxyl carrier (BCC) domain followed by the CC transfer of the carboxyl group from carboxylated biotin to acetyl-CoA CC (PubMed:19236960, PubMed:20457939, PubMed:20952656, PubMed:26976583). CC Through the production of malonyl-CoA that allosterically inhibits CC carnitine palmitoyltransferase 1 at the mitochondria, negatively CC regulates fatty acid oxidation (By similarity). Together with its CC cytosolic isozyme ACACA, which is involved in de novo fatty acid CC biosynthesis, promotes lipid storage (By similarity). CC {ECO:0000250|UniProtKB:E9Q4Z2, ECO:0000269|PubMed:16854592, CC ECO:0000269|PubMed:19236960, ECO:0000269|PubMed:19900410, CC ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, CC ECO:0000269|PubMed:26976583}. CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + ATP + hydrogencarbonate = ADP + H(+) + malonyl- CC CoA + phosphate; Xref=Rhea:RHEA:11308, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:456216; EC=6.4.1.2; CC Evidence={ECO:0000269|PubMed:16854592, ECO:0000269|PubMed:19236960, CC ECO:0000269|PubMed:19900410, ECO:0000269|PubMed:20457939, CC ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:26976583}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11309; CC Evidence={ECO:0000269|PubMed:19900410, ECO:0000269|PubMed:26976583}; CC -!- COFACTOR: CC Name=biotin; Xref=ChEBI:CHEBI:57586; CC Evidence={ECO:0000269|PubMed:16854592, ECO:0000269|PubMed:18247344}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00409, ECO:0000255|PROSITE-ProRule:PRU00969}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00409, ECO:0000255|PROSITE-ProRule:PRU00969}; CC Note=Binds 2 magnesium or manganese ions per subunit. CC {ECO:0000255|PROSITE-ProRule:PRU00409, ECO:0000255|PROSITE- CC ProRule:PRU00969}; CC -!- ACTIVITY REGULATION: Activity is increased by oligomerization of the CC protein into filaments (PubMed:19900410). The oligomerization and the CC activity of the enzyme are inhibited by phosphorylation at Ser-222 CC (PubMed:12488245). Inhibited by its product, malonyl-CoA CC (PubMed:16854592). Activated by citrate (PubMed:16854592). Activation CC by MID1IP1 is citrate-dependent (PubMed:20457939). Soraphen A, inhibits CC the enzyme by preventing the formation of active filamentous oligomers CC (Probable). {ECO:0000269|PubMed:12488245, ECO:0000269|PubMed:16854592, CC ECO:0000269|PubMed:19900410, ECO:0000269|PubMed:20457939, CC ECO:0000305|PubMed:19236960}. 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) {ECO:0000269|PubMed:19190759}; CC KM=6.5 mM for NaHCO3 (isoform 3) {ECO:0000269|PubMed:19190759}; CC KM=3 mM for NaHCO(3) {ECO:0000269|PubMed:16854592}; CC pH dependence: CC Optimum pH is 7.5. {ECO:0000305|PubMed:19236960}; CC -!- PATHWAY: Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from CC acetyl-CoA: step 1/1. {ECO:0000269|PubMed:19900410, CC ECO:0000269|PubMed:26976583}. CC -!- SUBUNIT: Monomer, homodimer, and homotetramer (PubMed:20952656, CC PubMed:18772397). Forms filamentous polymers (PubMed:20457939, CC PubMed:20952656, PubMed:19900410). Interacts with MID1IP1; interaction CC with MID1IP1 promotes oligomerization and increases its activity in a CC citrate-dependent manner (PubMed:20952656, PubMed:20457939). CC {ECO:0000269|PubMed:18772397, ECO:0000269|PubMed:19900410, CC ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656}. CC -!- INTERACTION: CC O00763; O00763: ACACB; NbExp=2; IntAct=EBI-2211739, EBI-2211739; CC O00763; P50747: HLCS; NbExp=4; IntAct=EBI-2211739, EBI-3915568; CC O00763; Q9CQ20: Mid1ip1; Xeno; NbExp=4; IntAct=EBI-2211739, EBI-473024; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10677481}. 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 {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 gland CC and colon (PubMed:9099716). Isoform 3 is expressed in skeletal muscle, CC adipose tissue and liver (at protein level) (PubMed:19190759). Isoform CC 3 is detected at high levels in adipose tissue with lower levels in CC heart, liver, skeletal muscle and testis (PubMed:19190759). CC {ECO:0000269|PubMed:19190759, ECO:0000269|PubMed:9099716}. CC -!- DOMAIN: Consists of an N-terminal biotin carboxylation/carboxylase (BC) CC domain that catalyzes the ATP-dependent transient carboxylation of the CC biotin covalently attached to the central biotinyl-binding/biotin CC carboxyl carrier (BCC) domain (Probable). The C-terminal carboxyl CC transferase (CT) domain catalyzes the transfer of the carboxyl group CC from carboxylated biotin to acetyl-CoA to produce malonyl-CoA CC (Probable). {ECO:0000305|PubMed:18247344, ECO:0000305|PubMed:19390150}. CC -!- PTM: The biotin cofactor is covalently attached to the central CC biotinyl-binding domain and is required for the catalytic activity. CC {ECO:0000305|PubMed:18247344}. CC -!- PTM: Phosphorylation at Ser-222 by AMPK inactivates the enzyme CC (PubMed:12488245). Required for the maintenance of skeletal muscle CC lipid and glucose homeostasis (By similarity). CC {ECO:0000250|UniProtKB:E9Q4Z2, ECO:0000269|PubMed:12488245}. CC -!- BIOTECHNOLOGY: Inhibition of ACACB may prevent lipid-induced insulin CC resistance and type 2 diabetes, making the enzyme a potential CC pharmaceutical target for treatment of obesity and type 2 diabetes. CC {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 https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) 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_005253876.4. DR RefSeq; XP_006719430.1; XM_006719367.3. DR RefSeq; XP_011536561.1; XM_011538259.2. 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 PDB; 5KKN; X-ray; 2.60 A; B/C=238-760. 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 PDBsum; 5KKN; -. DR AlphaFoldDB; O00763; -. DR SMR; O00763; -. DR BioGRID; 106550; 166. DR DIP; DIP-51617N; -. DR IntAct; O00763; 31. DR MINT; O00763; -. DR STRING; 9606.ENSP00000341044; -. DR BindingDB; O00763; -. DR ChEMBL; CHEMBL4829; -. DR DrugBank; DB03781; 2-[4-(2,4-Dichlorophenoxy)Phenoxy]Propanoic Acid. DR DrugBank; DB00173; Adenine. DR DrugBank; DB00121; Biotin. DR DrugBank; DB07870; Haloxyfop-P. DR DrugBank; DB02859; Soraphen A. DR GuidetoPHARMACOLOGY; 1264; -. DR SwissLipids; SLP:000000730; -. DR iPTMnet; O00763; -. DR PhosphoSitePlus; O00763; -. DR BioMuta; ACACB; -. DR EPD; O00763; -. DR jPOST; O00763; -. DR MassIVE; O00763; -. DR MaxQB; O00763; -. DR PaxDb; 9606-ENSP00000341044; -. DR PeptideAtlas; O00763; -. DR ProteomicsDB; 48022; -. [O00763-1] DR ProteomicsDB; 48023; -. [O00763-2] DR Antibodypedia; 1321; 185 antibodies from 30 providers. DR DNASU; 32; -. DR Ensembl; ENST00000338432.12; ENSP00000341044.7; ENSG00000076555.16. [O00763-1] DR Ensembl; ENST00000377848.7; ENSP00000367079.3; ENSG00000076555.16. [O00763-1] DR GeneID; 32; -. DR KEGG; hsa:32; -. DR MANE-Select; ENST00000338432.12; ENSP00000341044.7; NM_001093.4; NP_001084.3. DR UCSC; uc001tob.4; human. [O00763-1] DR AGR; HGNC:85; -. DR CTD; 32; -. DR DisGeNET; 32; -. DR GeneCards; ACACB; -. DR HGNC; HGNC:85; ACACB. DR HPA; ENSG00000076555; Tissue enhanced (adipose tissue, skeletal muscle). DR MIM; 601557; gene. DR neXtProt; NX_O00763; -. DR OpenTargets; ENSG00000076555; -. DR PharmGKB; PA24422; -. DR VEuPathDB; HostDB:ENSG00000076555; -. DR eggNOG; KOG0368; Eukaryota. DR GeneTree; ENSGT00940000155049; -. DR HOGENOM; CLU_000395_5_0_1; -. DR InParanoid; O00763; -. DR OMA; TEHCKVA; -. DR OrthoDB; 911at2759; -. DR PhylomeDB; O00763; -. DR TreeFam; TF300061; -. DR BioCyc; MetaCyc:HS01211-MONOMER; -. DR BRENDA; 6.3.4.14; 2681. DR BRENDA; 6.4.1.2; 2681. DR PathwayCommons; O00763; -. DR Reactome; R-HSA-163765; ChREBP activates metabolic gene expression. DR Reactome; R-HSA-196780; Biotin transport and metabolism. DR Reactome; R-HSA-200425; Carnitine metabolism. DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP). DR SABIO-RK; O00763; -. DR SignaLink; O00763; -. DR SIGNOR; O00763; -. DR UniPathway; UPA00655; UER00711. DR BioGRID-ORCS; 32; 8 hits in 1154 CRISPR screens. DR ChiTaRS; ACACB; human. DR EvolutionaryTrace; O00763; -. DR GeneWiki; ACACB; -. DR GenomeRNAi; 32; -. DR Pharos; O00763; Tchem. DR PRO; PR:O00763; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; O00763; Protein. DR Bgee; ENSG00000076555; Expressed in tendon of biceps brachii and 208 other cell types or tissues. DR ExpressionAtlas; O00763; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016507; C:mitochondrial fatty acid beta-oxidation multienzyme complex; IEA:Ensembl. 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:0042802; F:identical protein binding; IPI:IntAct. 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:0097009; P:energy homeostasis; IEA:Ensembl. DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central. DR GO; GO:0019395; P:fatty acid oxidation; IEA:Ensembl. DR GO; GO:0046323; P:glucose import; IEA:Ensembl. DR GO; GO:0090459; P:intracellular aspartate homeostasis; IEA:Ensembl. DR GO; GO:0090461; P:intracellular glutamate homeostasis; IEA:Ensembl. DR GO; GO:0046722; P:lactic acid secretion; IEA:Ensembl. DR GO; GO:2001295; P:malonyl-CoA biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0006098; P:pentose-phosphate shunt; IEA:Ensembl. DR GO; GO:0060421; P:positive regulation of heart growth; IEA:Ensembl. DR GO; GO:0010884; P:positive regulation of lipid storage; IEA:Ensembl. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR GO; GO:1903242; P:regulation of cardiac muscle hypertrophy in response to stress; IEA:Ensembl. DR GO; GO:0010906; P:regulation of glucose metabolic process; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0072350; P:tricarboxylic acid metabolic process; IEA:Ensembl. DR CDD; cd06850; biotinyl_domain; 1. DR Gene3D; 2.40.50.100; -; 1. DR Gene3D; 3.40.50.20; -; 1. DR Gene3D; 3.30.1490.20; ATP-grasp fold, A domain; 1. DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1. DR Gene3D; 2.40.460.10; Biotin dependent carboxylase carboxyltransferase; 1. DR Gene3D; 3.90.1770.10; PreATP-grasp domain; 1. DR InterPro; IPR049076; ACCA. DR InterPro; IPR049074; ACCA_BT. DR InterPro; IPR034733; AcCoA_carboxyl_beta. DR InterPro; IPR013537; AcCoA_COase_cen. DR InterPro; IPR011761; ATP-grasp. DR InterPro; IPR013815; ATP_grasp_subdomain_1. DR InterPro; IPR005481; BC-like_N. DR InterPro; IPR011764; Biotin_carboxylation_dom. DR InterPro; IPR005482; Biotin_COase_C. DR InterPro; IPR000089; Biotin_lipoyl. DR InterPro; IPR005479; CbamoylP_synth_lsu-like_ATP-bd. DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf. DR InterPro; IPR011763; COA_CT_C. DR InterPro; IPR011762; COA_CT_N. DR InterPro; IPR016185; PreATP-grasp_dom_sf. DR InterPro; IPR011054; Rudment_hybrid_motif. DR InterPro; IPR011053; Single_hybrid_motif. DR PANTHER; PTHR45728:SF1; ACETYL-COA CARBOXYLASE 2; 1. DR PANTHER; PTHR45728; ACETYL-COA CARBOXYLASE, ISOFORM A; 1. DR Pfam; PF08326; ACC_central; 1. DR Pfam; PF21385; ACCA_BT; 1. DR Pfam; PF02785; Biotin_carb_C; 1. DR Pfam; PF00289; Biotin_carb_N; 1. DR Pfam; PF00364; Biotin_lipoyl; 1. DR Pfam; PF01039; Carboxyl_trans; 1. DR Pfam; PF02786; CPSase_L_D2; 1. DR SMART; SM00878; Biotin_carb_C; 1. DR SUPFAM; SSF52096; ClpP/crotonase; 2. DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1. DR SUPFAM; SSF52440; PreATP-grasp domain; 1. DR SUPFAM; SSF51246; Rudiment single hybrid motif; 1. DR SUPFAM; SSF51230; Single hybrid motif; 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. DR Genevisible; O00763; HS. PE 1: Evidence at protein level; KW 3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding; Biotin; KW Fatty acid biosynthesis; Fatty acid metabolism; Ligase; Lipid biosynthesis; KW Lipid metabolism; Magnesium; Manganese; Metal-binding; Mitochondrion; KW Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Transit peptide. FT TRANSIT 1..? FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:E9Q4Z2" FT CHAIN ?..2458 FT /note="Acetyl-CoA carboxylase 2" FT /evidence="ECO:0000305" FT /id="PRO_0000146767" FT DOMAIN 259..761 FT /note="Biotin carboxylation" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00969" FT DOMAIN 414..609 FT /note="ATP-grasp" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT DOMAIN 888..962 FT /note="Biotinyl-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066" FT DOMAIN 1695..2025 FT /note="CoA carboxyltransferase N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01136" FT DOMAIN 2029..2345 FT /note="CoA carboxyltransferase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01137" FT REGION 35..155 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 174..193 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1695..2345 FT /note="Carboxyltransferase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01138" FT COMPBIAS 35..73 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 101..150 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 584 FT /evidence="ECO:0000250" FT BINDING 458..463 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 567 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409, FT ECO:0000255|PROSITE-ProRule:PRU00969" FT BINDING 567 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409, FT ECO:0000255|PROSITE-ProRule:PRU00969" FT BINDING 580 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409, FT ECO:0000255|PROSITE-ProRule:PRU00969" FT BINDING 580 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409, FT ECO:0000255|PROSITE-ProRule:PRU00969" FT BINDING 580 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409, FT ECO:0000255|PROSITE-ProRule:PRU00969" FT BINDING 580 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409, FT ECO:0000255|PROSITE-ProRule:PRU00969" FT BINDING 582 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409, FT ECO:0000255|PROSITE-ProRule:PRU00969" FT BINDING 582 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409, FT ECO:0000255|PROSITE-ProRule:PRU00969" FT BINDING 1934 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250" FT BINDING 2238 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250" FT BINDING 2240 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250" FT MOD_RES 35 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 70 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 91 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 95 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 169 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13085" FT MOD_RES 175 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13085" FT MOD_RES 192 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13085" FT MOD_RES 195 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13085" FT MOD_RES 200 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 207 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:E9Q4Z2" FT MOD_RES 220 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11497" FT MOD_RES 222 FT /note="Phosphoserine; by AMPK" FT /evidence="ECO:0000269|PubMed:12488245, FT ECO:0000269|PubMed:19900410" FT MOD_RES 469 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 753 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q13085" FT MOD_RES 929 FT /note="N6-biotinyllysine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066, FT ECO:0000269|PubMed:18247344" FT MOD_RES 1340 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:E9Q4Z2" FT MOD_RES 1342 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1360 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:E9Q4Z2" FT MOD_RES 1405 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13085" FT VAR_SEQ 1..202 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000269|PubMed:19190759" FT /id="VSP_057081" FT VAR_SEQ 203..218 FT /note="AYLTTGEAETRVPTMR -> MSPAKCKICFPDREVK (in isoform 3)" FT /evidence="ECO:0000269|PubMed:19190759" FT /id="VSP_057082" FT VAR_SEQ 1118..1187 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9099716" FT /id="VSP_000547" FT VARIANT 193 FT /note="R -> L (in a pancreatic ductal adenocarcinoma FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:18772397" FT /id="VAR_062667" FT VARIANT 552 FT /note="I -> V (in dbSNP:rs16940029)" FT /id="VAR_031255" FT VARIANT 651 FT /note="A -> T (in dbSNP:rs2300455)" FT /id="VAR_031256" FT VARIANT 2141 FT /note="V -> I (in dbSNP:rs2075260)" FT /evidence="ECO:0000269|PubMed:16854592, ECO:0000269|Ref.3" FT /id="VAR_031257" FT MUTAGEN 277 FT /note="R->A: Loss of regulation of oligomerization by FT phosphorylation at S-222." FT /evidence="ECO:0000269|PubMed:19900410" FT MUTAGEN 671 FT /note="E->A: Altered regulation of oligomerization by FT phosphorylation at S-222." FT /evidence="ECO:0000269|PubMed:19900410" FT CONFLICT 9 FT /note="C -> R (in Ref. 2; ABF48723)" FT /evidence="ECO:0000305" FT CONFLICT 120 FT /note="T -> I (in Ref. 4; AAR37018)" FT /evidence="ECO:0000305" FT CONFLICT 422 FT /note="I -> T (in Ref. 4; AAR37018)" FT /evidence="ECO:0000305" FT CONFLICT 1340 FT /note="S -> N (in Ref. 6; AAC50571)" FT /evidence="ECO:0000305" FT CONFLICT 1383 FT /note="D -> G (in Ref. 6; AAC50571)" FT /evidence="ECO:0000305" FT CONFLICT 1425 FT /note="V -> M (in Ref. 6; AAC50571)" FT /evidence="ECO:0000305" FT CONFLICT 1819..1821 FT /note="AEG -> PEA (in Ref. 6; AAC50571)" FT /evidence="ECO:0000305" FT CONFLICT 1892..1893 FT /note="MI -> IM (in Ref. 6; AAC50571)" FT /evidence="ECO:0000305" FT HELIX 247..253 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 262..265 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 269..287 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 292..299 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 301..305 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 309..313 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 314..319 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:3GLK" FT TURN 328..330 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 332..341 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 345..348 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 353..356 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 359..366 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 370..373 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 376..379 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 385..394 FT /evidence="ECO:0007829|PDB:3GLK" FT TURN 403..406 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 426..431 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 437..447 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 449..455 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 464..467 FT /evidence="ECO:0007829|PDB:3GLK" FT TURN 470..472 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 473..483 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 489..493 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 496..507 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 509..511 FT /evidence="ECO:0007829|PDB:3JRX" FT STRAND 513..523 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 524..527 FT /evidence="ECO:0007829|PDB:4HQ6" FT STRAND 530..535 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 541..558 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 562..571 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 572..574 FT /evidence="ECO:0007829|PDB:2HJW" FT STRAND 576..582 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 589..596 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 600..608 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 613..615 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 617..622 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 635..637 FT /evidence="ECO:0007829|PDB:2HJW" FT STRAND 646..653 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 669..671 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 679..685 FT /evidence="ECO:0007829|PDB:3GLK" FT STRAND 700..709 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 710..724 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 728..730 FT /evidence="ECO:0007829|PDB:2HJW" FT HELIX 732..742 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 744..748 FT /evidence="ECO:0007829|PDB:3GLK" FT HELIX 754..756 FT /evidence="ECO:0007829|PDB:2HJW" FT STRAND 896..898 FT /evidence="ECO:0007829|PDB:2DN8" FT STRAND 900..902 FT /evidence="ECO:0007829|PDB:2KCC" FT STRAND 903..910 FT /evidence="ECO:0007829|PDB:2DN8" FT STRAND 914..916 FT /evidence="ECO:0007829|PDB:2DN8" FT STRAND 921..927 FT /evidence="ECO:0007829|PDB:2DN8" FT STRAND 930..935 FT /evidence="ECO:0007829|PDB:2DN8" FT STRAND 937..944 FT /evidence="ECO:0007829|PDB:2DN8" FT STRAND 957..961 FT /evidence="ECO:0007829|PDB:2DN8" FT TURN 1698..1700 FT /evidence="ECO:0007829|PDB:3FF6" FT HELIX 1703..1711 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1717..1719 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1720..1732 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1742..1750 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1756..1759 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1767..1777 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1786..1793 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1798..1800 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1804..1820 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1824..1828 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1839..1842 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1846..1850 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1855..1857 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1859..1864 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1866..1872 FT /evidence="ECO:0007829|PDB:3TDC" FT TURN 1873..1876 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1878..1885 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1888..1896 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1899..1901 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1905..1924 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1927..1931 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1933..1936 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1938..1946 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1948..1952 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1956..1960 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1962..1969 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1977..1981 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1983..1986 FT /evidence="ECO:0007829|PDB:3TDC" FT TURN 1987..1990 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 1993..1998 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 1999..2010 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2045..2050 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2055..2057 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2072..2075 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2082..2089 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2092..2099 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2104..2108 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2120..2124 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2131..2147 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2151..2154 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2164..2168 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2171..2183 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2189..2193 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2198..2200 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2201..2205 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2209..2211 FT /evidence="ECO:0007829|PDB:3TDC" FT TURN 2213..2215 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2216..2221 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2225..2229 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2231..2238 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2241..2251 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2253..2261 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2269..2299 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2300..2302 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2304..2309 FT /evidence="ECO:0007829|PDB:3TDC" FT STRAND 2312..2317 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2319..2321 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2322..2344 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2345..2348 FT /evidence="ECO:0007829|PDB:3FF6" FT HELIX 2352..2365 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2369..2376 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2378..2388 FT /evidence="ECO:0007829|PDB:3TDC" FT HELIX 2404..2420 FT /evidence="ECO:0007829|PDB:3TDC" FT TURN 2423..2425 FT /evidence="ECO:0007829|PDB:3FF6" FT HELIX 2426..2435 FT /evidence="ECO:0007829|PDB:3FF6" FT HELIX 2439..2448 FT /evidence="ECO:0007829|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 //