ACACA_HUMAN
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 03-AUG-2022, entry version 217.
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;
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 -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01066,
CC 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";
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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_011523005.1; XM_011524703.1. [Q13085-1]
DR RefSeq; XP_016880044.1; XM_017024555.1. [Q13085-1]
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 SMR; Q13085; -.
DR BioGRID; 106549; 345.
DR DIP; DIP-36122N; -.
DR ELM; Q13085; -.
DR IntAct; Q13085; 64.
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; Q13085; -.
DR PeptideAtlas; Q13085; -.
DR PRIDE; Q13085; -.
DR ProteomicsDB; 59139; -. [Q13085-1]
DR ProteomicsDB; 59140; -. [Q13085-2]
DR ProteomicsDB; 59141; -. [Q13085-3]
DR ProteomicsDB; 59142; -. [Q13085-4]
DR ABCD; Q13085; 1 sequenced antibody.
DR Antibodypedia; 73364; 653 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 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; LIQCAMP; -.
DR OrthoDB; 156081at2759; -.
DR PhylomeDB; Q13085; -.
DR TreeFam; TF300061; -.
DR BioCyc; MetaCyc:HS05598-MON; -.
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; 215 hits in 1092 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 102 other tissues.
DR ExpressionAtlas; Q13085; baseline and differential.
DR Genevisible; Q13085; HS.
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 Gene3D; 3.30.1490.20; -; 1.
DR IDEAL; IID00610; -.
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; 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 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; 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.
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
