ACACB_HUMAN
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 03-AUG-2022, entry version 207.
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;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409,
CC ECO:0000255|PROSITE-ProRule:PRU00969};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409,
CC 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=3.0 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};
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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. [O00763-3]
DR RefSeq; XP_011536561.1; XM_011538259.2. [O00763-1]
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; 108.
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; O00763; -.
DR PeptideAtlas; O00763; -.
DR PRIDE; O00763; -.
DR ProteomicsDB; 48022; -. [O00763-1]
DR ProteomicsDB; 48023; -. [O00763-2]
DR Antibodypedia; 1321; 188 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 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; CGRDSTL; -.
DR OrthoDB; 861989at2759; -.
DR PhylomeDB; O00763; -.
DR TreeFam; TF300061; -.
DR BioCyc; MetaCyc:HS01211-MON; -.
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 1073 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 206 other tissues.
DR ExpressionAtlas; O00763; baseline and differential.
DR Genevisible; O00763; HS.
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: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:2001295; P:malonyl-CoA biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IEA:Ensembl.
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: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:0010906; P:regulation of glucose metabolic process; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; 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 Gene3D; 3.30.1490.20; -; 1.
DR InterPro; IPR034733; AcCoA_carboxyl.
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 Pfam; PF08326; ACC_central; 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; 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; 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
