ID ACACA_HUMAN Reviewed; 2346 AA. AC Q13085; B2RP68; B2ZZ90; Q6KEV6; Q6XDA8; Q7Z2G8; Q7Z561; Q7Z563; Q7Z564; AC Q86WB2; Q86WB3; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 226. DE RecName: Full=Acetyl-CoA carboxylase 1 {ECO:0000303|PubMed:12810950}; DE Short=ACC1; DE EC=6.4.1.2 {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}; DE AltName: Full=Acetyl-Coenzyme A carboxylase alpha; DE Short=ACC-alpha; GN Name=ACACA {ECO:0000312|HGNC:HGNC:84}; Synonyms=ACAC, ACC1, ACCA; 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] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=7732023; DOI=10.1073/pnas.92.9.4011; RA Abu-Elheiga L., Jayakumar A., Baldini A., Chirala S.S., Wakil S.J.; RT "Human acetyl-CoA carboxylase: characterization, molecular cloning, and RT evidence for two isoforms."; RL Proc. Natl. Acad. Sci. U.S.A. 92:4011-4015(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 1-366 RP (ISOFORMS 2 AND 3), AND NUCLEOTIDE SEQUENCE [MRNA] OF 1-120 (ISOFORM 4). RC TISSUE=Adipocyte; RX PubMed=12810950; DOI=10.1073/pnas.1332670100; RA Mao J., Chirala S.S., Wakil S.J.; RT "Human acetyl-CoA carboxylase 1 gene: presence of three promoters and RT heterogeneity at the 5'-untranslated mRNA region."; RL Proc. Natl. Acad. Sci. U.S.A. 100:7515-7520(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-2271. RX PubMed=15333468; DOI=10.1093/carcin/bgh273; RA Sinilnikova O.M., Ginolhac S.M., Magnard C., Leone M., Anczukow O., RA Hughes D., Moreau K., Thompson D., Coutanson C., Hall J., Romestaing P., RA Gerard J.-P., Bonadona V., Lasset C., Goldgar D.E., Joulin V., RA Venezia N.D., Lenoir G.M.; RT "Acetyl-CoA carboxylase alpha gene and breast cancer susceptibility."; RL Carcinogenesis 25:2417-2424(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=18487259; DOI=10.1093/dnares/dsn010; RA Oshikawa M., Sugai Y., Usami R., Ohtoko K., Toyama S., Kato S.; RT "Fine expression profiling of full-length transcripts using a size-unbiased RT cDNA library prepared with the vector-capping method."; RL DNA Res. 15:123-136(2008). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-113 (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [MRNA] OF 1-93 (ISOFORM 3). RC TISSUE=Mammary gland, and Testis; RX PubMed=14643797; DOI=10.1016/j.bbalip.2003.09.005; RA Travers M.T., Vallance A.J., Clegg R.A., Thomson R., Price N.T., RA Barber M.C.; RT "Characterisation of an N-terminal variant of acetyl-CoA carboxylase-alpha: RT expression in human tissues and evolutionary aspects."; RL Biochim. Biophys. Acta 1634:97-106(2003). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-47 (ISOFORM 1). RC TISSUE=Testis; RX PubMed=15607423; DOI=10.1016/j.ygeno.2004.10.001; RA Travers M.T., Cambot M., Kennedy H.T., Lenoir G.M., Barber M.C., Joulin V.; RT "Asymmetric expression of transcripts derived from the shared promoter RT between the divergently oriented ACACA and TADA2L genes."; RL Genomics 85:71-84(2005). RN [9] RP PROTEIN SEQUENCE OF 1-18; 39-45; 77-86; 99-111; 121-132; 153-170; 218-224; RP 267-276; 278-288; 323-335; 568-579; 589-615; 646-657; 748-755; 818-838; RP 985-992; 997-1008; 1083-1096; 1147-1169; 1192-1199; 1233-1247; 1283-1294; RP 1317-1325; 1327-1334; 1372-1385; 1401-1420; 1508-1514; 1553-1564; RP 1668-1687; 1714-1731; 1750-1759; 1782-1798; 1824-1833; 1838-1856; RP 1905-1916; 1922-1929; 1978-2009; 2063-2072; 2104-2111; 2115-2127; RP 2139-2161; 2200-2209; 2213-2218; 2221-2229 AND 2261-2293, ACETYLATION AT RP MET-1, PHOSPHORYLATION AT SER-80, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Hepatoma; RA Bienvenut W.V., Boldt K., von Kriegsheim A.F., Kolch W.; RL Submitted (JUL-2007) to UniProtKB. RN [10] RP INTERACTION WITH BRCA1. RX PubMed=12360400; DOI=10.1038/sj.onc.1205915; RA Magnard C., Bachelier R., Vincent A., Jaquinod M., Kieffer S., Lenoir G.M., RA Venezia N.D.; RT "BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT RT domains."; RL Oncogene 21:6729-6739(2002). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-29 AND SER-53, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [12] RP INTERACTION WITH BRCA1, AND ACTIVITY REGULATION. RX PubMed=16326698; DOI=10.1074/jbc.m504652200; RA Moreau K., Dizin E., Ray H., Luquain C., Lefai E., Foufelle F., Billaud M., RA Lenoir G.M., Venezia N.D.; RT "BRCA1 affects lipid synthesis through its interaction with acetyl-CoA RT carboxylase."; RL J. Biol. Chem. 281:3172-3181(2006). RN [13] RP PHOSPHORYLATION AT SER-1263, AND MUTAGENESIS OF SER-78; SER-344; SER-432; RP SER-1201; SER-1263; SER-1585; SER-1952 AND SER-2211. RX PubMed=16698035; DOI=10.1016/j.jmb.2006.04.010; RA Ray H., Moreau K., Dizin E., Callebaut I., Venezia N.D.; RT "ACCA phosphopeptide recognition by the BRCT repeats of BRCA1."; RL J. Mol. Biol. 359:973-982(2006). RN [14] RP INVOLVEMENT IN ACACAD. RX PubMed=6114432; DOI=10.1056/nejm198108203050820; RA Blom W., de Muinck Keizer S.M.P.F., Scholte H.R.; RT "Acetyl-CoA carboxylase deficiency: an inborn error of de novo fatty acid RT synthesis."; RL N. Engl. J. Med. 305:465-466(1981). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-29, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-25; SER-29 AND RP SER-80, AND 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 [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-5 AND SER-29, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-25 AND SER-29, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1334, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [22] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT, AND INTERACTION WITH RP 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 [23] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT, 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 [24] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-5; SER-23; SER-29; SER-48 AND SER-80, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-29 AND SER-80, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-25; SER-29; SER-80; RP THR-610; SER-835 AND THR-2153, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25; SER-29 AND SER-1273, AND RP IDENTIFICATION BY MASS SPECTROMETRY [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 [29] RP X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) OF 1258-1270 IN COMPLEX WITH BRCA1, RP AND INTERACTION WITH BRCA1. RX PubMed=18452305; DOI=10.1021/bi800314m; RA Shen Y., Tong L.; RT "Structural evidence for direct interactions between the BRCT domains of RT human BRCA1 and a phospho-peptide from human ACC1."; RL Biochemistry 47:5767-5773(2008). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 78-617. RA Muniz J.R.C., Froese D.S., Krysztofinska E., Vollmar M., Beltrami A., RA Krojer T., Allerston C.K., von Delft F., Arrowsmith C.H., Edwards A.M., RA Weigelt J., Bountra C., Yue W.W., Oppermann U.; RT "Crystal Structure of Human Acetyl-Coa Carboxylase 1, Biotin Carboxylase RT (Bc) Domain."; RL Submitted (MAY-2011) to the PDB data bank. RN [31] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1571-2338. RA Froese D.S., Muniz J.R.C., Kiyani W., Krojer T., Vollmar M., von Delft F., RA Bountra C., Arrowsmith C.H., Edwards A., Oppermann U., Yue W.W.; RT "Crystal Structure of Human Acaca C-Terminal Domain."; RL Submitted (MAY-2012) to the PDB data bank. RN [32] RP STRUCTURE BY ELECTRON MICROSCOPY (4.60 ANGSTROMS) OF OLIGOMER IN COMPLEX RP WITH BRCA1 BRCT DOMAIN, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY RP REGULATION, SUBUNIT, INTERACTION WITH BRCA1, DOMAIN, BIOTINYLATION, AND RP PHOSPHORYLATION AT SER-80 AND SER-1263. RX PubMed=29899443; DOI=10.1038/s41586-018-0201-4; RA Hunkeler M., Hagmann A., Stuttfeld E., Chami M., Guri Y., Stahlberg H., RA Maier T.; RT "Structural basis for regulation of human acetyl-CoA carboxylase."; RL Nature 558:470-474(2018). RN [33] RP VARIANT [LARGE SCALE ANALYSIS] GLN-1687. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Cytosolic enzyme that catalyzes the carboxylation of acetyl- CC CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty CC acid biosynthesis (PubMed:20952656, PubMed:20457939, PubMed:29899443). CC This is a 2 steps reaction starting with the ATP-dependent CC carboxylation of the biotin carried by the biotin carboxyl carrier CC (BCC) domain followed by the transfer of the carboxyl group from CC carboxylated biotin to acetyl-CoA (PubMed:20952656, PubMed:20457939, CC PubMed:29899443). {ECO:0000269|PubMed:20457939, CC ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. 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:20457939, ECO:0000269|PubMed:20952656, CC ECO:0000269|PubMed:29899443}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11309; CC Evidence={ECO:0000305|PubMed:20457939}; 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 -!- COFACTOR: CC Name=biotin; Xref=ChEBI:CHEBI:57586; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU01066, ECO:0000269|PubMed:29899443}; CC -!- ACTIVITY REGULATION: Inhibited by phosphorylation (PubMed:16326698, CC PubMed:29899443). Citrate promotes oligomerization of the protein into CC filaments that correspond to the most active form of the carboxylase CC (PubMed:29899443). Inhibited by palmitoyl-CoA (PubMed:29899443). CC {ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:29899443}. CC -!- PATHWAY: Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from CC acetyl-CoA: step 1/1. {ECO:0000305|PubMed:20457939, CC ECO:0000305|PubMed:20952656}. CC -!- SUBUNIT: Monomer, homodimer, and homotetramer (PubMed:20952656, CC PubMed:29899443). Can form filamentous polymers (PubMed:20457939, CC PubMed:20952656, PubMed:29899443). Interacts in its inactive CC phosphorylated form with the BRCT domains of BRCA1 which prevents ACACA CC dephosphorylation and inhibits lipid synthesis (PubMed:12360400, CC PubMed:16326698, PubMed:18452305, PubMed:29899443). Interacts with CC MID1IP1; interaction with MID1IP1 promotes oligomerization and CC increases its activity (PubMed:20457939). {ECO:0000269|PubMed:12360400, CC ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:18452305, CC ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, CC ECO:0000269|PubMed:29899443}. CC -!- INTERACTION: CC Q13085; Q13085: ACACA; NbExp=2; IntAct=EBI-717681, EBI-717681; CC Q13085; O60218: AKR1B10; NbExp=4; IntAct=EBI-717681, EBI-1572139; CC Q13085; P38398: BRCA1; NbExp=2; IntAct=EBI-717681, EBI-349905; CC Q13085; Q96EB6: SIRT1; NbExp=3; IntAct=EBI-717681, EBI-1802965; CC Q13085; Q9CQ20: Mid1ip1; Xeno; NbExp=4; IntAct=EBI-717681, EBI-473024; CC Q13085-4; P02654: APOC1; NbExp=3; IntAct=EBI-12562760, EBI-1220105; CC Q13085-4; Q92915-2: FGF14; NbExp=3; IntAct=EBI-12562760, EBI-12836320; CC Q13085-4; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-12562760, EBI-17589229; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q5SWU9}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=4; CC Name=1; CC IsoId=Q13085-1; Sequence=Displayed; CC Name=2; Synonyms=E5A; CC IsoId=Q13085-2; Sequence=VSP_026099; CC Name=3; Synonyms=E5B; CC IsoId=Q13085-3; Sequence=VSP_026098; CC Name=4; CC IsoId=Q13085-4; Sequence=VSP_026100; CC -!- TISSUE SPECIFICITY: Expressed in brain, placenta, skeletal muscle, CC renal, pancreatic and adipose tissues; expressed at low level in CC pulmonary tissue; not detected in the liver. 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:29899443}. CC -!- PTM: Phosphorylation on Ser-1263 is required for interaction with CC BRCA1. {ECO:0000269|PubMed:16698035, ECO:0000269|Ref.9}. CC -!- PTM: Phosphorylation at Ser-80 by AMPK inactivates enzyme activity. CC {ECO:0000250|UniProtKB:P11497}. CC -!- PTM: The biotin cofactor is covalently attached to the central CC biotinyl-binding domain and is required for the catalytic activity. CC {ECO:0000269|PubMed:29899443}. CC -!- DISEASE: Acetyl-CoA carboxylase 1 deficiency (ACACAD) [MIM:613933]: An CC inborn error of de novo fatty acid synthesis associated with severe CC brain damage, persistent myopathy and poor growth. CC {ECO:0000269|PubMed:6114432}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Acetyl-CoA carboxylase entry; CC URL="https://en.wikipedia.org/wiki/Acetyl-CoA_carboxylase"; 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; U19822; AAC50139.1; -; mRNA. DR EMBL; AY315619; AAP94114.1; -; mRNA. DR EMBL; AY315620; AAP94115.1; -; mRNA. DR EMBL; AY315621; AAP94116.1; -; mRNA. DR EMBL; AY315623; AAP94118.1; -; mRNA. DR EMBL; AY315627; AAP94122.1; -; mRNA. DR EMBL; AY237919; AAP69841.1; -; mRNA. DR EMBL; AB371587; BAG48316.1; -; mRNA. DR EMBL; CH471199; EAW57582.1; -; Genomic_DNA. DR EMBL; CH471199; EAW57577.1; -; Genomic_DNA. DR EMBL; CH471199; EAW57578.1; -; Genomic_DNA. DR EMBL; CH471199; EAW57581.1; -; Genomic_DNA. DR EMBL; BC137287; AAI37288.1; -; mRNA. DR EMBL; AJ534888; CAD59556.1; -; mRNA. DR EMBL; AJ534889; CAD59557.1; -; mRNA. DR EMBL; AJ564444; CAD92089.1; -; mRNA. DR CCDS; CCDS11317.1; -. [Q13085-1] DR CCDS; CCDS11318.1; -. [Q13085-2] DR CCDS; CCDS42302.1; -. [Q13085-4] DR CCDS; CCDS42303.1; -. [Q13085-3] DR PIR; I38928; I38928. DR RefSeq; NP_942131.1; NM_198834.2. [Q13085-4] DR RefSeq; NP_942133.1; NM_198836.2. [Q13085-1] DR RefSeq; NP_942134.1; NM_198837.1. [Q13085-2] DR RefSeq; NP_942135.1; NM_198838.1. [Q13085-3] DR RefSeq; NP_942136.1; NM_198839.2. [Q13085-1] DR RefSeq; XP_005257324.1; XM_005257267.4. [Q13085-3] DR RefSeq; XP_011523005.1; XM_011524703.1. [Q13085-1] DR RefSeq; XP_011523006.1; XM_011524704.2. [Q13085-3] DR RefSeq; XP_016880044.1; XM_017024555.1. DR PDB; 2YL2; X-ray; 2.30 A; A/B=78-617. DR PDB; 3COJ; X-ray; 3.21 A; H/I/J/K/L/M/N/O=1258-1270. DR PDB; 4ASI; X-ray; 2.80 A; A/B/C/D/E/F=1571-2338. DR PDB; 6G2D; EM; 5.40 A; B/C/D/F=1-2346. DR PDB; 6G2H; EM; 4.60 A; A/B/C/D/E/F=1-2346. DR PDB; 6G2I; EM; 5.90 A; A/B/C/D/E/F/G/J/Q/R=1-2346. DR PDBsum; 2YL2; -. DR PDBsum; 3COJ; -. DR PDBsum; 4ASI; -. DR PDBsum; 6G2D; -. DR PDBsum; 6G2H; -. DR PDBsum; 6G2I; -. DR AlphaFoldDB; Q13085; -. DR EMDB; EMD-4342; -. DR EMDB; EMD-4343; -. DR EMDB; EMD-4344; -. DR SMR; Q13085; -. DR BioGRID; 106549; 464. DR DIP; DIP-36122N; -. DR ELM; Q13085; -. DR IntAct; Q13085; 70. DR MINT; Q13085; -. DR STRING; 9606.ENSP00000483300; -. DR BindingDB; Q13085; -. DR ChEMBL; CHEMBL3351; -. DR DrugBank; DB00121; Biotin. DR GuidetoPHARMACOLOGY; 1263; -. DR SwissLipids; SLP:000000729; -. DR GlyGen; Q13085; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13085; -. DR PhosphoSitePlus; Q13085; -. DR SwissPalm; Q13085; -. DR BioMuta; ACACA; -. DR DMDM; 118601083; -. DR CPTAC; CPTAC-782; -. DR EPD; Q13085; -. DR jPOST; Q13085; -. DR MassIVE; Q13085; -. DR MaxQB; Q13085; -. DR PaxDb; 9606-ENSP00000483300; -. DR PeptideAtlas; Q13085; -. DR ProteomicsDB; 59139; -. [Q13085-1] DR ProteomicsDB; 59140; -. [Q13085-2] DR ProteomicsDB; 59141; -. [Q13085-3] DR ProteomicsDB; 59142; -. [Q13085-4] DR Pumba; Q13085; -. DR ABCD; Q13085; 1 sequenced antibody. DR Antibodypedia; 73364; 835 antibodies from 39 providers. DR DNASU; 31; -. DR Ensembl; ENST00000611803.2; ENSP00000479901.1; ENSG00000275176.4. [Q13085-2] DR Ensembl; ENST00000612895.4; ENSP00000482269.1; ENSG00000278540.5. [Q13085-2] DR Ensembl; ENST00000613687.4; ENSP00000483674.1; ENSG00000275176.4. [Q13085-1] DR Ensembl; ENST00000614428.4; ENSP00000478547.1; ENSG00000278540.5. [Q13085-1] DR Ensembl; ENST00000616317.5; ENSP00000483300.1; ENSG00000278540.5. [Q13085-4] DR Ensembl; ENST00000617649.4; ENSP00000482368.1; ENSG00000278540.5. [Q13085-3] DR Ensembl; ENST00000619487.4; ENSP00000478577.1; ENSG00000275176.4. [Q13085-4] DR Ensembl; ENST00000621312.4; ENSP00000480031.1; ENSG00000275176.4. [Q13085-3] DR GeneID; 31; -. DR KEGG; hsa:31; -. DR MANE-Select; ENST00000616317.5; ENSP00000483300.1; NM_198834.3; NP_942131.1. [Q13085-4] DR UCSC; uc002hnk.4; human. [Q13085-1] DR AGR; HGNC:84; -. DR CTD; 31; -. DR DisGeNET; 31; -. DR GeneCards; ACACA; -. DR HGNC; HGNC:84; ACACA. DR HPA; ENSG00000278540; Low tissue specificity. DR MalaCards; ACACA; -. DR MIM; 200350; gene. DR MIM; 613933; phenotype. DR neXtProt; NX_Q13085; -. DR OpenTargets; ENSG00000278540; -. DR PharmGKB; PA24421; -. DR VEuPathDB; HostDB:ENSG00000278540; -. DR eggNOG; KOG0368; Eukaryota. DR GeneTree; ENSGT00940000156706; -. DR HOGENOM; CLU_000395_5_0_1; -. DR InParanoid; Q13085; -. DR OMA; PTPKGHC; -. DR OrthoDB; 911at2759; -. DR PhylomeDB; Q13085; -. DR TreeFam; TF300061; -. DR BioCyc; MetaCyc:HS05598-MONOMER; -. DR BRENDA; 6.4.1.2; 2681. DR PathwayCommons; Q13085; -. 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 Reactome; R-HSA-3371599; Defective HLCS causes multiple carboxylase deficiency. DR Reactome; R-HSA-75105; Fatty acyl-CoA biosynthesis. DR SABIO-RK; Q13085; -. DR SignaLink; Q13085; -. DR SIGNOR; Q13085; -. DR UniPathway; UPA00655; UER00711. DR BioGRID-ORCS; 31; 225 hits in 1172 CRISPR screens. DR ChiTaRS; ACACA; human. DR EvolutionaryTrace; Q13085; -. DR GeneWiki; ACACA; -. DR GenomeRNAi; 31; -. DR Pharos; Q13085; Tchem. DR PRO; PR:Q13085; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q13085; Protein. DR Bgee; ENSG00000278540; Expressed in cortical plate and 104 other cell types or tissues. DR ExpressionAtlas; Q13085; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0003989; F:acetyl-CoA carboxylase activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. 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; ISS:UniProtKB. DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl. DR GO; GO:0006633; P:fatty acid biosynthetic process; ISS:UniProtKB. DR GO; GO:0046949; P:fatty-acyl-CoA biosynthetic process; TAS:Reactome. DR GO; GO:0055088; P:lipid homeostasis; IEA:Ensembl. DR GO; GO:2001295; P:malonyl-CoA biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB. DR GO; GO:0019538; P:protein metabolic process; IEA:Ensembl. DR GO; GO:0001894; P:tissue homeostasis; 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 IDEAL; IID00610; -. 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; IPR001882; Biotin_BS. 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:SF5; ACETYL-COA CARBOXYLASE 1; 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; PS00188; BIOTIN; 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; Q13085; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Allosteric enzyme; Alternative promoter usage; KW ATP-binding; Biotin; Cytoplasm; Direct protein sequencing; KW Fatty acid biosynthesis; Fatty acid metabolism; Ligase; Lipid biosynthesis; KW Lipid metabolism; Magnesium; Manganese; Metal-binding; KW Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; KW Reference proteome. FT CHAIN 1..2346 FT /note="Acetyl-CoA carboxylase 1" FT /id="PRO_0000146764" FT DOMAIN 117..618 FT /note="Biotin carboxylation" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00969" FT DOMAIN 275..466 FT /note="ATP-grasp" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT DOMAIN 745..819 FT /note="Biotinyl-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066" FT DOMAIN 1576..1914 FT /note="CoA carboxyltransferase N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01136" FT DOMAIN 1918..2234 FT /note="CoA carboxyltransferase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01137" FT REGION 1576..2234 FT /note="Carboxyltransferase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01138" FT ACT_SITE 441 FT /evidence="ECO:0000250" FT BINDING 315..320 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409" FT BINDING 424 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 424 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 437 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 437 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 437 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 437 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 439 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 439 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 1823 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250" FT BINDING 2127 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250" FT BINDING 2129 FT /ligand="CoA" FT /ligand_id="ChEBI:CHEBI:57287" FT /evidence="ECO:0000250" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:20068231" FT MOD_RES 5 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231" FT MOD_RES 25 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 29 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 34 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11497" FT MOD_RES 48 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 50 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11497" FT MOD_RES 53 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 58 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q5SWU9" FT MOD_RES 78 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11497" FT MOD_RES 80 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:29899443, ECO:0000269|Ref.9, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 488 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336" FT MOD_RES 610 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 786 FT /note="N6-biotinyllysine" FT /evidence="ECO:0000250|UniProtKB:P11497, FT ECO:0000255|PROSITE-ProRule:PRU01066" FT MOD_RES 835 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1201 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11497" FT MOD_RES 1216 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11497" FT MOD_RES 1218 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5SWU9" FT MOD_RES 1227 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q5SWU9" FT MOD_RES 1259 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5SWU9" FT MOD_RES 1263 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16698035, FT ECO:0000269|PubMed:29899443" FT MOD_RES 1273 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1334 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 2153 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..78 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12810950, FT ECO:0000303|PubMed:14643797" FT /id="VSP_026098" FT VAR_SEQ 1..75 FT /note="MDEPSPLAQPLELNQHSRFIIGSVSEDNSEDEISNLVKLDLLEEKEGSLSPA FT SVGSDTLSDLGISSLQDGLALHI -> MEGSPEENKEMRYYMLQ (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:12810950, FT ECO:0000303|PubMed:14643797" FT /id="VSP_026099" FT VAR_SEQ 1 FT /note="M -> MWWSTLMSILRARSFWKWISTQTVRIIRAVRAHFGGIM (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:12810950, FT ECO:0000303|PubMed:15489334" FT /id="VSP_026100" FT VARIANT 838 FT /note="R -> W (in dbSNP:rs2287351)" FT /id="VAR_042941" FT VARIANT 1687 FT /note="R -> Q (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs1357271377)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036514" FT VARIANT 2271 FT /note="A -> V (frequency <0.004; may play a role in breast FT cancer susceptibility; dbSNP:rs146351326)" FT /evidence="ECO:0000269|PubMed:15333468" FT /id="VAR_028929" FT MUTAGEN 78 FT /note="S->A: No effect on interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:16698035" FT MUTAGEN 344 FT /note="S->A: No effect on interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:16698035" FT MUTAGEN 432 FT /note="S->A: No effect on interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:16698035" FT MUTAGEN 1201 FT /note="S->A: No effect on interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:16698035" FT MUTAGEN 1263 FT /note="S->A: Abolishes interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:16698035" FT MUTAGEN 1585 FT /note="S->A: No effect on interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:16698035" FT MUTAGEN 1952 FT /note="S->A: No effect on interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:16698035" FT MUTAGEN 2211 FT /note="S->A: No effect on interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:16698035" FT CONFLICT 66 FT /note="S -> A (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 79 FT /note="M -> W (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 89 FT /note="R -> G (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 182 FT /note="P -> A (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 234 FT /note="S -> N (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 299 FT /note="Q -> K (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 303 FT /note="E -> K (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 364 FT /note="A -> V (in Ref. 2; AAP94122)" FT /evidence="ECO:0000305" FT CONFLICT 446 FT /note="H -> Q (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 494 FT /note="D -> N (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 554 FT /note="D -> G (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 622 FT /note="Q -> R (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 640 FT /note="A -> G (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 814 FT /note="V -> I (in Ref. 2; AAP94122)" FT /evidence="ECO:0000305" FT CONFLICT 1061 FT /note="N -> S (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1094..1095 FT /note="EL -> DV (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1225 FT /note="S -> A (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1257 FT /note="S -> C (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1297 FT /note="C -> G (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1320 FT /note="V -> A (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1444 FT /note="N -> S (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1474 FT /note="F -> L (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1665..1666 FT /note="TF -> SL (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1677 FT /note="I -> V (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1741 FT /note="P -> S (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1762 FT /note="S -> G (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1822 FT /note="C -> S (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1875 FT /note="M -> T (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1888 FT /note="D -> G (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 1997 FT /note="I -> V (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 2013 FT /note="Q -> H (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 2058 FT /note="D -> H (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 2075 FT /note="C -> S (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 2098..2099 FT /note="SS -> PT (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 2158..2159 FT /note="TA -> PT (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 2166 FT /note="N -> S (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 2234 FT /note="N -> S (in Ref. 1; AAC50139)" FT /evidence="ECO:0000305" FT CONFLICT 2321 FT /note="H -> R (in Ref. 2; AAP94122)" FT /evidence="ECO:0000305" FT HELIX 105..111 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 120..123 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 127..145 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 150..157 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 159..163 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 168..171 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 172..177 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 183..185 FT /evidence="ECO:0007829|PDB:2YL2" FT TURN 186..188 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 190..199 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 203..206 FT /evidence="ECO:0007829|PDB:2YL2" FT TURN 211..214 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 217..224 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 228..231 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 234..241 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 243..252 FT /evidence="ECO:0007829|PDB:2YL2" FT TURN 261..264 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 283..289 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 294..304 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 306..312 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 320..324 FT /evidence="ECO:0007829|PDB:2YL2" FT TURN 327..329 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 330..340 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 346..350 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 356..364 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 370..382 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 385..392 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 398..415 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 419..427 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 433..439 FT /evidence="ECO:0007829|PDB:2YL2" FT TURN 444..446 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 447..453 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 457..465 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 470..472 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 474..479 FT /evidence="ECO:0007829|PDB:2YL2" FT TURN 492..495 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 496..498 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 503..510 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 526..530 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 537..542 FT /evidence="ECO:0007829|PDB:2YL2" FT STRAND 557..566 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 567..582 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 589..599 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 601..604 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 612..616 FT /evidence="ECO:0007829|PDB:2YL2" FT HELIX 1582..1592 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1598..1600 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1601..1619 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1628..1631 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1632..1639 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1645..1648 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1656..1666 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1675..1682 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1687..1689 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1693..1709 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1713..1717 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1728..1731 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1735..1739 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1744..1746 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1748..1753 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1755..1761 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1762..1764 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1767..1774 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1777..1785 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1795..1813 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1816..1820 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1822..1825 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1827..1834 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1837..1841 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1845..1849 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1851..1858 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1866..1870 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1872..1875 FT /evidence="ECO:0007829|PDB:4ASI" FT TURN 1876..1879 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1882..1887 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1888..1899 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1914..1917 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 1934..1939 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1944..1946 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1961..1964 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1971..1978 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1981..1988 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 1993..1996 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 2010..2013 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2020..2036 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 2040..2043 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2053..2057 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2060..2072 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 2078..2082 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 2087..2089 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2090..2094 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2098..2100 FT /evidence="ECO:0007829|PDB:4ASI" FT TURN 2102..2104 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 2105..2110 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 2114..2118 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2120..2127 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2130..2140 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2142..2150 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2158..2188 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2193..2198 FT /evidence="ECO:0007829|PDB:4ASI" FT STRAND 2201..2206 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2208..2210 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2211..2235 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2241..2256 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2258..2265 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2267..2278 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2289..2310 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2312..2314 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2315..2322 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2323..2325 FT /evidence="ECO:0007829|PDB:4ASI" FT HELIX 2328..2337 FT /evidence="ECO:0007829|PDB:4ASI" SQ SEQUENCE 2346 AA; 265554 MW; F1F0A518F8824FFC CRC64; MDEPSPLAQP LELNQHSRFI IGSVSEDNSE DEISNLVKLD LLEEKEGSLS PASVGSDTLS DLGISSLQDG LALHIRSSMS GLHLVKQGRD RKKIDSQRDF TVASPAEFVT RFGGNKVIEK VLIANNGIAA VKCMRSIRRW SYEMFRNERA IRFVVMVTPE DLKANAEYIK MADHYVPVPG GPNNNNYANV ELILDIAKRI PVQAVWAGWG HASENPKLPE LLLKNGIAFM GPPSQAMWAL GDKIASSIVA QTAGIPTLPW SGSGLRVDWQ ENDFSKRILN VPQELYEKGY VKDVDDGLQA AEEVGYPVMI KASEGGGGKG IRKVNNADDF PNLFRQVQAE VPGSPIFVMR LAKQSRHLEV QILADQYGNA ISLFGRDCSV QRRHQKIIEE APATIATPAV FEHMEQCAVK LAKMVGYVSA GTVEYLYSQD GSFYFLELNP RLQVEHPCTE MVADVNLPAA QLQIAMGIPL YRIKDIRMMY GVSPWGDSPI DFEDSAHVPC PRGHVIAARI TSENPDEGFK PSSGTVQELN FRSNKNVWGY FSVAAAGGLH EFADSQFGHC FSWGENREEA ISNMVVALKE LSIRGDFRTT VEYLIKLLET ESFQMNRIDT GWLDRLIAEK VQAERPDTML GVVCGALHVA DVSLRNSVSN FLHSLERGQV LPAHTLLNTV DVELIYEGVK YVLKVTRQSP NSYVVIMNGS CVEVDVHRLS DGGLLLSYDG SSYTTYMKEE VDRYRITIGN KTCVFEKEND PSVMRSPSAG KLIQYIVEDG GHVFAGQCYA EIEVMKMVMT LTAVESGCIH YVKRPGAALD PGCVLAKMQL DNPSKVQQAE LHTGSLPRIQ STALRGEKLH RVFHYVLDNL VNVMNGYCLP DPFFSSKVKD WVERLMKTLR DPSLPLLELQ DIMTSVSGRI PPNVEKSIKK EMAQYASNIT SVLCQFPSQQ IANILDSHAA TLNRKSEREV FFMNTQSIVQ LVQRYRSGIR GHMKAVVMDL LRQYLRVETQ FQNGHYDKCV FALREENKSD MNTVLNYIFS HAQVTKKNLL VTMLIDQLCG RDPTLTDELL NILTELTQLS KTTNAKVALR ARQVLIASHL PSYELRHNQV ESIFLSAIDM YGHQFCIENL QKLILSETSI FDVLPNFFYH SNQVVRMAAL EVYVRRAYIA YELNSVQHRQ LKDNTCVVEF QFMLPTSHPN RGNIPTLNRM SFSSNLNHYG MTHVASVSDV LLDNSFTPPC QRMGGMVSFR TFEDFVRIFD EVMGCFSDSP PQSPTFPEAG HTSLYDEDKV PRDEPIHILN VAIKTDCDIE DDRLAAMFRE FTQQNKATLV DHGIRRLTFL VAQKDFRKQV NYEVDRRFHR EFPKFFTFRA RDKFEEDRIY RHLEPALAFQ LELNRMRNFD LTAIPCANHK MHLYLGAAKV EVGTEVTDYR FFVRAIIRHS DLVTKEASFE YLQNEGERLL LEAMDELEVA FNNTNVRTDC NHIFLNFVPT VIMDPSKIEE SVRSMVMRYG SRLWKLRVLQ AELKINIRLT PTGKAIPIRL FLTNESGYYL DISLYKEVTD SRTAQIMFQA YGDKQGPLHG MLINTPYVTK DLLQSKRFQA QSLGTTYIYD IPEMFRQSLI KLWESMSTQA FLPSPPLPSD MLTYTELVLD DQGQLVHMNR LPGGNEIGMV AWKMTFKSPE YPEGRDIIVI GNDITYRIGS FGPQEDLLFL RASELARAEG IPRIYVSANS GARIGLAEEI RHMFHVAWVD PEDPYKGYRY LYLTPQDYKR VSALNSVHCE HVEDEGESRY KITDIIGKEE GIGPENLRGS GMIAGESSLA YNEIITISLV TCRAIGIGAY LVRLGQRTIQ VENSHLILTG AGALNKVLGR EVYTSNNQLG GIQIMHNNGV THCTVCDDFE GVFTVLHWLS YMPKSVHSSV PLLNSKDPID RIIEFVPTKT PYDPRWMLAG RPHPTQKGQW LSGFFDYGSF SEIMQPWAQT VVVGRARLGG IPVGVVAVET RTVELSIPAD PANLDSEAKI IQQAGQVWFP DSAFKTYQAI KDFNREGLPL MVFANWRGFS GGMKDMYDQV LKFGAYIVDG LRECCQPVLV YIPPQAELRG GSWVVIDSSI NPRHMEMYAD RESRGSVLEP EGTVEIKFRR KDLVKTMRRV DPVYIHLAER LGTPELSTAE RKELENKLKE REEFLIPIYH QVAVQFADLH DTPGRMQEKG VISDILDWKT SRTFFYWRLR RLLLEDLVKK KIHNANPELT DGQIQAMLRR WFVEVEGTVK AYVWDNNKDL AEWLEKQLTE EDGVHSVIEE NIKCISRDYV LKQIRSLVQA NPEVAMDSII HMTQHISPTQ RAEVIRILST MDSPST //