ACACB_MOUSE
ID ACACB_MOUSE Reviewed; 2448 AA.
AC E9Q4Z2; Q6JIZ0;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Acetyl-CoA carboxylase 2 {ECO:0000250|UniProtKB:O00763};
DE EC=6.4.1.2 {ECO:0000250|UniProtKB:O00763};
DE AltName: Full=ACC-beta {ECO:0000250|UniProtKB:O00763};
DE Flags: Precursor;
GN Name=Acacb {ECO:0000312|MGI:MGI:2140940};
GN Synonyms=Acc2 {ECO:0000303|PubMed:10677481},
GN Accb {ECO:0000312|MGI:MGI:2140940};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|Ensembl:ENSMUSP00000099642};
RN [1] {ECO:0000312|EMBL:AAS13686.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAS13686.1};
RC TISSUE=Heart {ECO:0000312|EMBL:AAS13686.1};
RA Mao J., Wakil S.J.;
RT "Alternative splicing in the mouse acetyl-CoA carboxylase 2 (ACC2) gene.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|Ensembl:ENSMUSP00000031583}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000031583};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000305}
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 [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11283375; DOI=10.1126/science.1056843;
RA Abu-Elheiga L., Matzuk M.M., Abo-Hashema K.A., Wakil S.J.;
RT "Continuous fatty acid oxidation and reduced fat storage in mice lacking
RT acetyl-CoA carboxylase 2.";
RL Science 291:2613-2616(2001).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12920182; DOI=10.1073/pnas.1733877100;
RA Abu-Elheiga L., Oh W., Kordari P., Wakil S.J.;
RT "Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and
RT diabetes induced by high-fat/high-carbohydrate diets.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:10207-10212(2003).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15677334; DOI=10.1073/pnas.0409451102;
RA Oh W., Abu-Elheiga L., Kordari P., Gu Z., Shaikenov T., Chirala S.S.,
RA Wakil S.J.;
RT "Glucose and fat metabolism in adipose tissue of acetyl-CoA carboxylase 2
RT knockout mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1384-1389(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [8] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18487439; DOI=10.1152/ajpheart.91489.2007;
RA Essop M.F., Camp H.S., Choi C.S., Sharma S., Fryer R.M., Reinhart G.A.,
RA Guthrie P.H., Bentebibel A., Gu Z., Shulman G.I., Taegtmeyer H.,
RA Wakil S.J., Abu-Elheiga L.;
RT "Reduced heart size and increased myocardial fuel substrate oxidation in
RT ACC2 mutant mice.";
RL Am. J. Physiol. 295:H256-H265(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47; THR-197; SER-459;
RP SER-1330; SER-1332 AND SER-1350, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=20368432; DOI=10.1073/pnas.0913492107;
RA Olson D.P., Pulinilkunnil T., Cline G.W., Shulman G.I., Lowell B.B.;
RT "Gene knockout of Acc2 has little effect on body weight, fat mass, or food
RT intake.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:7598-7603(2010).
RN [11] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=22730442; DOI=10.1161/circresaha.112.268128;
RA Kolwicz S.C. Jr., Olson D.P., Marney L.C., Garcia-Menendez L.,
RA Synovec R.E., Tian R.;
RT "Cardiac-specific deletion of acetyl CoA carboxylase 2 prevents metabolic
RT remodeling during pressure-overload hypertrophy.";
RL Circ. Res. 111:728-738(2012).
RN [12]
RP INDUCTION BY ENDOCANNABINOID ANANDAMIDE.
RX PubMed=21987372; DOI=10.1002/hep.24733;
RA Jourdan T., Demizieux L., Gresti J., Djaouti L., Gaba L., Verges B.,
RA Degrace P.;
RT "Antagonism of peripheral hepatic cannabinoid receptor-1 improves liver
RT lipid metabolism in mice: evidence from cultured explants.";
RL Hepatology 55:790-799(2012).
RN [13] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22362781; DOI=10.1074/jbc.m111.309559;
RA Abu-Elheiga L., Wu H., Gu Z., Bressler R., Wakil S.J.;
RT "Acetyl-CoA carboxylase 2-/- mutant mice are protected against fatty liver
RT under high-fat, high-carbohydrate dietary and de novo lipogenic
RT conditions.";
RL J. Biol. Chem. 287:12578-12588(2012).
RN [14] {ECO:0000305}
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT SER-212 BY AMPK, AND
RP MUTAGENESIS OF SER-212.
RX PubMed=24913514; DOI=10.1007/s00125-014-3273-1;
RA O'Neill H.M., Lally J.S., Galic S., Thomas M., Azizi P.D., Fullerton M.D.,
RA Smith B.K., Pulinilkunnil T., Chen Z., Samaan M.C., Jorgensen S.B.,
RA Dyck J.R., Holloway G.P., Hawke T.J., van Denderen B.J., Kemp B.E.,
RA Steinberg G.R.;
RT "AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid
RT oxidation and insulin sensitivity in mice.";
RL Diabetologia 57:1693-1702(2014).
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 (By similarity). Catalyzes a 2 steps reaction starting with
CC the ATP-dependent carboxylation of the biotin carried by the biotin
CC carboxyl carrier (BCC) domain followed by the transfer of the carboxyl
CC group from carboxylated biotin to acetyl-CoA (By similarity). Through
CC the production of malonyl-CoA that allosterically inhibits carnitine
CC palmitoyltransferase 1 at the mitochondria, negatively regulates fatty
CC acid oxidation (PubMed:24913514). Together with its cytosolic isozyme
CC ACACA, which is involved in de novo fatty acid biosynthesis, promotes
CC lipid storage (PubMed:24913514). {ECO:0000250|UniProtKB:O00763,
CC ECO:0000269|PubMed:24913514}.
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:0000250|UniProtKB:O00763};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11309;
CC Evidence={ECO:0000250|UniProtKB:O00763};
CC -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC Evidence={ECO:0000250|UniProtKB:O00763};
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 that correspond to the most active form of the
CC carboxylase. The oligomerization and the activity of the enzyme are
CC inhibited by phosphorylation at Ser-212 (PubMed:24913514). Inhibited by
CC its own product malonyl-CoA. Activation by MID1IP1 is citrate
CC dependent. {ECO:0000250|UniProtKB:O00763, ECO:0000269|PubMed:24913514}.
CC -!- PATHWAY: Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from
CC acetyl-CoA: step 1/1. {ECO:0000250|UniProtKB:O00763}.
CC -!- SUBUNIT: Monomer, homodimer, and homotetramer. Forms filamentous
CC polymers. Interacts with MID1IP1; interaction with MID1IP1 promotes
CC oligomerization and increases its activity in a citrate-dependent
CC manner. {ECO:0000250|UniProtKB:O00763}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10677481}.
CC -!- INDUCTION: Up-regulated by endocannabinoid anandamide/AEA.
CC {ECO:0000269|PubMed:21987372}.
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 (By similarity). 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 (By
CC similarity). {ECO:0000250|UniProtKB:O00763}.
CC -!- PTM: The biotin cofactor is covalently attached to the central
CC biotinyl-binding domain and is required for the catalytic activity.
CC {ECO:0000250|UniProtKB:O00763}.
CC -!- PTM: Phosphorylated by AMPK at Ser-212 inactivates the enzyme
CC (PubMed:24913514). Required for the maintenance of skeletal muscle
CC lipid and glucose homeostasis (PubMed:24913514).
CC {ECO:0000269|PubMed:24913514}.
CC -!- DISRUPTION PHENOTYPE: Normal morphology, fertility, growth rate and
CC lifespan but higher than normal food consumption and fatty acid
CC oxidation rate and decreased fat content in adipose tissue and liver
CC (PubMed:11283375). A high-fat/high-carbohydrate diet results in
CC maintenance of normal insulin and glucose levels with less weight gain
CC and less fat accumulation than wild-type mice (PubMed:12920182).
CC Elevated levels of Ucp2 in adipose tissue and heart but not in skeletal
CC muscle or liver, and elevated levels of Ucp3 in skeletal muscle but not
CC in heart or brown adipose tissue (PubMed:12920182). Significant
CC decrease in body weight, weight of epidydimal fat pads and levels of
CC hepatic triglycerides under a range of dietary conditions including
CC normal chow diet, fasting and refeeding a fat-free high-carbohydrate
CC diet, and a high-fat/high-carbohydrate diet (PubMed:22362781). Up-
CC regulation of lipogenic enzymes under de novo lipogenic conditions but
CC reduced fat accumulation in liver (PubMed:22362781). Primary cultured
CC adipocytes show increased fatty acid and glucose oxidation rates and
CC increased lipolysis (PubMed:15677334). Reduced heart size, reduced
CC Mlycd and malonyl-CoA levels in mutant hearts, reduced myocardial
CC triglyceride levels, higher myocardial oleate and glucose oxidation
CC rates, reduced levels of Ppara and reduced activation of Mtor
CC (PubMed:18487439, PubMed:22730442). However, it has also been reported
CC that mutants show no differences in body weight, food intake, body
CC composition or glucose homeostasis as compared with controls fed on
CC chow or a high-fat diet (PubMed:20368432).
CC {ECO:0000269|PubMed:11283375, ECO:0000269|PubMed:12920182,
CC ECO:0000269|PubMed:15677334, ECO:0000269|PubMed:18487439,
CC ECO:0000269|PubMed:20368432, ECO:0000269|PubMed:22362781,
CC ECO:0000269|PubMed:22730442}.
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DR EMBL; AY451394; AAS13686.1; -; mRNA.
DR EMBL; AC122282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS19561.1; -.
DR RefSeq; NP_598665.2; NM_133904.2.
DR RefSeq; XP_006530176.1; XM_006530113.3.
DR AlphaFoldDB; E9Q4Z2; -.
DR SMR; E9Q4Z2; -.
DR BioGRID; 221514; 2.
DR IntAct; E9Q4Z2; 1.
DR STRING; 10090.ENSMUSP00000099642; -.
DR BindingDB; E9Q4Z2; -.
DR ChEMBL; CHEMBL3108631; -.
DR iPTMnet; E9Q4Z2; -.
DR PhosphoSitePlus; E9Q4Z2; -.
DR SwissPalm; E9Q4Z2; -.
DR EPD; E9Q4Z2; -.
DR jPOST; E9Q4Z2; -.
DR MaxQB; E9Q4Z2; -.
DR PaxDb; E9Q4Z2; -.
DR PeptideAtlas; E9Q4Z2; -.
DR PRIDE; E9Q4Z2; -.
DR ProteomicsDB; 286028; -.
DR Antibodypedia; 1321; 188 antibodies from 30 providers.
DR DNASU; 100705; -.
DR Ensembl; ENSMUST00000031583; ENSMUSP00000031583; ENSMUSG00000042010.
DR Ensembl; ENSMUST00000102582; ENSMUSP00000099642; ENSMUSG00000042010.
DR GeneID; 100705; -.
DR KEGG; mmu:100705; -.
DR UCSC; uc008yzi.2; mouse.
DR CTD; 32; -.
DR MGI; MGI:2140940; Acacb.
DR VEuPathDB; HostDB:ENSMUSG00000042010; -.
DR eggNOG; KOG0368; Eukaryota.
DR GeneTree; ENSGT00940000155049; -.
DR HOGENOM; CLU_000395_5_0_1; -.
DR InParanoid; E9Q4Z2; -.
DR OMA; CGRDSTL; -.
DR OrthoDB; 156081at2759; -.
DR PhylomeDB; E9Q4Z2; -.
DR TreeFam; TF300061; -.
DR BRENDA; 6.4.1.2; 3474.
DR Reactome; R-MMU-163765; ChREBP activates metabolic gene expression.
DR Reactome; R-MMU-196780; Biotin transport and metabolism.
DR Reactome; R-MMU-200425; Carnitine metabolism.
DR UniPathway; UPA00655; UER00711.
DR BioGRID-ORCS; 100705; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Acacb; mouse.
DR PRO; PR:E9Q4Z2; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; E9Q4Z2; protein.
DR Bgee; ENSMUSG00000042010; Expressed in brown adipose tissue and 118 other tissues.
DR ExpressionAtlas; E9Q4Z2; baseline and differential.
DR Genevisible; E9Q4Z2; MM.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0003989; F:acetyl-CoA carboxylase activity; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; ISO:MGI.
DR GO; GO:0097009; P:energy homeostasis; IMP:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IMP:MGI.
DR GO; GO:2001295; P:malonyl-CoA biosynthetic process; IMP:UniProtKB.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; IMP:UniProtKB.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IMP:UniProtKB.
DR GO; GO:0060421; P:positive regulation of heart growth; IMP:UniProtKB.
DR GO; GO:0010884; P:positive regulation of lipid storage; IMP:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISO:MGI.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB.
DR GO; GO:0031667; P:response to nutrient levels; IMP:UniProtKB.
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 Allosteric enzyme; ATP-binding; Biotin; Fatty acid biosynthesis;
KW Fatty acid metabolism; Ligase; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Manganese; Metal-binding; Mitochondrion; Multifunctional enzyme;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000303|PubMed:10677481"
FT CHAIN ?..2448
FT /note="Acetyl-CoA carboxylase 2"
FT /evidence="ECO:0000303|PubMed:10677481"
FT /id="PRO_0000430774"
FT DOMAIN 249..751
FT /note="Biotin carboxylation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00969"
FT DOMAIN 408..599
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT DOMAIN 878..952
FT /note="Biotinyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 1685..2015
FT /note="CoA carboxyltransferase N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01136"
FT DOMAIN 2019..2335
FT /note="CoA carboxyltransferase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01137"
FT REGION 48..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 159..213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1685..2335
FT /note="Carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01138"
FT COMPBIAS 71..109
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..205
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 574
FT /evidence="ECO:0000250|UniProtKB:P24182"
FT BINDING 434..491
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 557
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 557
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 570
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 570
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 570
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 570
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 572
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 572
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 1924
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q00955"
FT BINDING 2228
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q00955"
FT BINDING 2230
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q00955"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00763"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00763"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00763"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13085"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13085"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11497"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13085"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13085"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00763"
FT MOD_RES 197
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11497"
FT MOD_RES 212
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:24913514"
FT MOD_RES 459
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 743
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13085"
FT MOD_RES 919
FT /note="N6-biotinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11497,
FT ECO:0000255|PROSITE-ProRule:PRU01066"
FT MOD_RES 1330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1332
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1350
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13085"
FT MUTAGEN 212
FT /note="S->A: No phosphorylation by AMPK, reduced fatty acid
FT oxidation in skeletal muscle, increased lipid deposition in
FT skeletal muscle, and development of insulin resistance."
FT /evidence="ECO:0000269|PubMed:24913514"
FT CONFLICT 124
FT /note="S -> P (in Ref. 1; AAS13686)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="F -> S (in Ref. 1; AAS13686)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="Q -> R (in Ref. 1; AAS13686)"
FT /evidence="ECO:0000305"
FT CONFLICT 1315
FT /note="F -> S (in Ref. 1; AAS13686)"
FT /evidence="ECO:0000305"
FT CONFLICT 1402
FT /note="S -> N (in Ref. 1; AAS13686)"
FT /evidence="ECO:0000305"
FT CONFLICT 2341
FT /note="N -> S (in Ref. 1; AAS13686)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2448 AA; 275750 MW; 6CD686C7AF012A5E CRC64;
MVLLLFLTCL VFSCLTFSWL KIWGKMTDSK PLTNSKVEAN LLSSEESLSA SELSGEQLQE
HGDHSCLSYR GPRDASQQRN SLPSSCQRPP RNPLSSNDTW PSPELQTNWT AAPGPEVPDA
NGLSFPARPP SQRTVSPSRE DRKQAHIKRQ LMTSFILGSL DDNSSDEDPS AGSFQNSSRK
SSRASLGTLS QEAALNTSDP ESHAPTMRPS MSGLHLVKRG REHKKLDLHR DFTVASPAEF
VTRFGGNRVI EKVLIANNGI AAVKCMRSIR RWAYEMFRNE RAIRFVVMVT PEDLKANAEY
IKMADQYVPV PGGPNNNNYA NVELIIDIAK RIPVQAVWAG WGHASENPKL PELLCKHEIA
FLGPPSEAMW ALGDKIASTI VAQTLQIPTL PWSGSGLTVE WTEDSRHQGK CISVPEDVYE
QGCVKDVDEG LQAAEKIGFP LMIKASEGGG GKGIRKAESA EDFPMLFRQV QSEIPGSPIF
LMKLAQNARH LEVQVLADQY GNAVSLFGRD CSIQRRHQKI IEEAPATIAA PAVFEFMEQC
AVLLAKMVGY VSAGTVEYLY SQDGSFHFLE LNPRLQVEHP CTEMIADVNL PAAQLQIAMG
VPLHRLKDIR LLYGESPWGV TPIPFETPLS PPIARGHVIA ARITSENPDE GFKPSSGTVQ
ELNFRSNKNV WGYFSVAAAG GLHEFADSQF GHCFSWGENR EEAISNMVVA LKELSIRGDF
RTTVEYLVNL LETESFQNND IDTGWLDHLI AQRVQAEKPD IMLGVVCGAL NVADAMFRTC
MTEFLHSLER GQVLPADSLL NIVDVELIYG GIKYALKVAR QSLTMFVLIM NGCHIEIDAH
RLNDGGLLLS YNGSSYTTYM KEEVDSYRIT IGNKTCVFEK ENDPTVLRSP SAGKLMQYTV
EDGDHVEAGS SYAEMEVMKM IMTLNVQESG RVKYIKRPGV ILEAGCVVAR LELDDPSKVH
AAQPFTGELP AQQTLPILGE KLHQVFHGVL ENLTNVMSGY CLPEPFFSMK LKDWVQKLMM
TLRHPSLPLL ELQEIMTSVA GRIPAPVEKA VRRVMAQYAS NITSVLCQFP SQQIATILDC
HAATLQRKAD REVFFMNTQS IVQLVQRYRS GTRGYMKAVV LDLLRKYLNV EHHFQQAHYD
KCVINLREQF KPDMTQVLDC IFSHSQVAKK NQLVTMLIDE LCGPDPTLSD ELTSILCELT
QLSRSEHCKV ALRARQVLIA SHLPSYELRH NQVESIFLSA IDMYGHQFCP ENLKKLILSE
TTIFDVLPTF FYHENKVVCM ASLEVYVRRG YIAYELNSLQ HRELPDGTCV VEFQFMLPSS
HPNRMAVPIS VSNPDLLRHS TELFMDSGFS PLCQRMGAMV AFRRFEEFTR NFDEVISCFA
NVQTDTLLFS KACTSLYSEE DSKSLREEPI HILNVAIQCA DHMEDEALVP VFRAFVQSKK
HILVDYGLRR ITFLVAQERE FPKFFTFRAR DEFAEDRIYR HLEPALAFQL ELSRMRNFDL
TAVPCANHKM HLYLGAAKVK EGLEVTDHRF FIRAIIRHSD LITKEASFEY LQNEGERLLL
EAMDELEVAF NNTSVRTDCN HIFLNFVPTV IMDPLKIEES VRDMVMRYGS RLWKLRVLQA
EVKINIRQTT SDSAIPIRLF ITNESGYYLD ISLYREVTDS RSGNIMFHSF GNKQGSLHGM
LINTPYVTKD LLQAKRFQAQ SLGTTYVYDF PEMFRQALFK LWGSPEKYPK DILTYTELVL
DSQGQLVEMN RLPGCNEVGM VAFKMRFKTP EYPEGRDAVV IGNDITFQIG SFGIGEDFLY
LRASEMARTE GIPQIYLAAN SGARMGLAEE IKQIFQVAWV DPEDPHKGFR YLYLTPQDYT
QISSQNSVHC KHIEDEGESR YVIVDVIGKD ANLGVENLRG SGMIAGEASL AYEKTVTISM
VTCRALGIGA YLVRLGQRVI QVENSHIILT GAGALNKVLG REVYTSNNQL GGVQIMHTNG
VSHVTVPDDF EGVCTILEWL SFIPKDNRSP VPITTPSDPI DREIEFTPTK APYDPRWMLA
GRPHPTLKGT WQSGFFDHGS FKEIMAPWAQ TVVTGRARLG GIPVGVIAVE TRTVEVAVPA
DPANLDSEAK IIQQAGQVWF PDSAYKTAQV IRDFNKERLP LMIFANWRGF SGGMKDMYEQ
MLKFGAYIVD GLRLYEQPIL IYIPPCAELR GGSWVVLDST INPLCIEMYA DKESRGGVLE
PEGTVEIKFR KKDLVKTIRR IDPVCKKLVG QLGKAQLPDK DRKELEGQLK AREELLLPIY
HQVAVQFADL HDTPGHMLEK GIISDVLEWK TARTFFYWRL RRLLLEAQVK QEILRASPEL
NHEHTQSMLR RWFVETEGAV KAYLWDSNQV VVQWLEQHWS AKDGLRSTIR ENINYLKRDS
VLKTIQSLVQ EHPEVIMDCV AYLSQHLTPA ERIQVAQLLS TTESPASS
