ACLY_HUMAN
ID ACLY_HUMAN Reviewed; 1101 AA.
AC P53396; B4DIM0; B4E3P0; Q13037; Q9BRL0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=ATP-citrate synthase;
DE EC=2.3.3.8 {ECO:0000269|PubMed:10653665, ECO:0000269|PubMed:1371749, ECO:0000269|PubMed:19286649, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:9116495};
DE AltName: Full=ATP-citrate (pro-S-)-lyase;
DE Short=ACL;
DE AltName: Full=Citrate cleavage enzyme;
GN Name=ACLY;
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), FUNCTION, CATALYTIC ACTIVITY,
RP MUTAGENESIS OF HIS-760, AND VARIANT ASP-175.
RC TISSUE=Liver;
RX PubMed=1371749; DOI=10.1111/j.1432-1033.1992.tb16659.x;
RA Elshourbagy N.A., Near J.C., Kmetz P.J., Wells T.N.C., Groot P.H.E.,
RA Saxty B.A., Hughes S.A., Franklin M., Gloger I.S.;
RT "Cloning and expression of a human ATP-citrate lyase cDNA.";
RL Eur. J. Biochem. 204:491-499(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND VARIANT
RP ASP-175.
RC TISSUE=Liver;
RX PubMed=9116495; DOI=10.1006/prep.1996.0668;
RA Lord K.A., Wang X.M., Simmons S.J., Bruckner R.C., Loscig J., O'Connor B.,
RA Bentley R., Smallwood A., Chadwick C.C., Stevis P.E., Ciccarelli R.B.;
RT "Variant cDNA sequences of human ATP:citrate lyase: cloning, expression,
RT and purification from baculovirus-infected insect cells.";
RL Protein Expr. Purif. 9:133-141(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT
RP ASP-175.
RC TISSUE=Hippocampus, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND PHOSPHORYLATION.
RX PubMed=10653665; DOI=10.1021/bi992159y;
RA Potapova I.A., El-Maghrabi M.R., Doronin S.V., Benjamin W.B.;
RT "Phosphorylation of recombinant human ATP:citrate lyase by cAMP-dependent
RT protein kinase abolishes homotropic allosteric regulation of the enzyme by
RT citrate and increases the enzyme activity. Allosteric activation of
RT ATP:citrate lyase by phosphorylated sugars.";
RL Biochemistry 39:1169-1179(2000).
RN [7]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-131 AND TYR-682, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY
RP 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455; SER-481 AND SER-1100,
RP 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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19286649; DOI=10.1194/jlr.d900008-jlr200;
RA Ma Z., Chu C.H., Cheng D.;
RT "A novel direct homogeneous assay for ATP citrate lyase.";
RL J. Lipid Res. 50:2131-2135(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481; THR-639; SER-663;
RP TYR-682; SER-839 AND SER-1100, 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY
RP 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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-546; LYS-554; LYS-948; LYS-968
RP AND LYS-1077, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455 AND SER-481, AND
RP IDENTIFICATION 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 [19]
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455 AND SER-481, 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455; SER-459 AND SER-481, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [22]
RP FUNCTION, ACETYLATION AT LYS-540; LYS-546 AND LYS-554, UBIQUITINATION AT
RP LYS-540; LYS-546 AND LYS-554, MUTAGENESIS OF LYS-540; LYS-546 AND LYS-554,
RP AND CATALYTIC ACTIVITY.
RX PubMed=23932781; DOI=10.1016/j.molcel.2013.07.002;
RA Lin R., Tao R., Gao X., Li T., Zhou X., Guan K.L., Xiong Y., Lei Q.Y.;
RT "Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and
RT tumor growth.";
RL Mol. Cell 51:506-518(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455 AND SER-481, 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 [24]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-425 AND 487-820 IN COMPLEX WITH
RP CITRATE, AND CITRATE-BINDING SITES.
RX PubMed=20558738; DOI=10.1074/jbc.m109.078667;
RA Sun T., Hayakawa K., Bateman K.S., Fraser M.E.;
RT "Identification of the citrate-binding site of human ATP-citrate lyase
RT using X-ray crystallography.";
RL J. Biol. Chem. 285:27418-27428(2010).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-817 IN COMPLEX WITH ADP.
RX PubMed=22102020; DOI=10.1107/s1744309111028363;
RA Sun T., Hayakawa K., Fraser M.E.;
RT "ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase.";
RL Acta Crystallogr. F 67:1168-1172(2011).
CC -!- FUNCTION: Catalyzes the cleavage of citrate into oxaloacetate and
CC acetyl-CoA, the latter serving as common substrate for de novo
CC cholesterol and fatty acid synthesis. {ECO:0000269|PubMed:10653665,
CC ECO:0000269|PubMed:1371749, ECO:0000269|PubMed:19286649,
CC ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:9116495}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + ADP + oxaloacetate + phosphate = ATP + citrate +
CC CoA; Xref=Rhea:RHEA:21160, ChEBI:CHEBI:16452, ChEBI:CHEBI:16947,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:456216; EC=2.3.3.8;
CC Evidence={ECO:0000269|PubMed:10653665, ECO:0000269|PubMed:1371749,
CC ECO:0000269|PubMed:19286649, ECO:0000269|PubMed:23932781,
CC ECO:0000269|PubMed:9116495};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21162;
CC Evidence={ECO:0000305|PubMed:10653665, ECO:0000305|PubMed:1371749,
CC ECO:0000305|PubMed:19286649, ECO:0000305|PubMed:23932781,
CC ECO:0000305|PubMed:9116495};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19286649};
CC -!- ACTIVITY REGULATION: Phosphorylation results in activation of its
CC activity (PubMed:10653665). Glucose 6-phosphate, fructose 6-phosphate,
CC fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-
CC bisphosphate also act as activators (PubMed:10653665).
CC {ECO:0000269|PubMed:10653665}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=98.0 uM for citrate {ECO:0000269|PubMed:9116495};
CC KM=73.8 uM for citrate {ECO:0000269|PubMed:19286649};
CC KM=127 uM for citrate (phosphorylated form by PKA)
CC {ECO:0000269|PubMed:10653665};
CC KM=149 uM for citrate (phosphorylated form by both PKA and GSK3)
CC {ECO:0000269|PubMed:10653665};
CC KM=14.0 uM for CoA {ECO:0000269|PubMed:9116495};
CC KM=4.0 uM for CoA {ECO:0000269|PubMed:19286649};
CC KM=2.59 uM for CoA (unphosphorylated form)
CC {ECO:0000269|PubMed:10653665};
CC KM=2.32 uM for CoA (unphosphorylated form in the presence of fructose
CC 6-phosphate) {ECO:0000269|PubMed:10653665};
CC KM=2.01 uM for CoA (phosphorylated form by PKA)
CC {ECO:0000269|PubMed:10653665};
CC KM=2.35 uM for CoA (phosphorylated form by PKA in the presence of
CC fructose 6-phosphate) {ECO:0000269|PubMed:10653665};
CC KM=2.28 uM for CoA (phosphorylated form by both PKA and GSK3)
CC {ECO:0000269|PubMed:10653665};
CC KM=2.09 uM for CoA (phosphorylated form by both PKA and GSK3 in the
CC presence of fructose 6-phosphate) {ECO:0000269|PubMed:10653665};
CC KM=120.0 uM for ATP {ECO:0000269|PubMed:9116495};
CC KM=47.0 uM for ATP {ECO:0000269|PubMed:19286649};
CC KM=41.0 uM for ATP (unphosphorylated form)
CC {ECO:0000269|PubMed:10653665};
CC KM=2.89 uM for ATP (unphosphorylated form in the presence of fructose
CC 6-phosphate) {ECO:0000269|PubMed:10653665};
CC KM=41.15 uM for ATP (phosphorylated form by PKA)
CC {ECO:0000269|PubMed:10653665};
CC KM=4.79 uM for ATP (phosphorylated form by PKA in the presence of
CC fructose 6-phosphate) {ECO:0000269|PubMed:10653665};
CC KM=37.28 uM for ATP (phosphorylated form by both PKA and GSK3)
CC {ECO:0000269|PubMed:10653665};
CC KM=4.01 uM for ATP (phosphorylated form by both PKA and GSK3 in the
CC presence of fructose 6-phosphate) {ECO:0000269|PubMed:10653665};
CC Vmax=1.9 umol/h/ug enzyme {ECO:0000269|PubMed:9116495};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:20558738,
CC ECO:0000269|PubMed:22102020, ECO:0000269|PubMed:9116495}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:9116495}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P53396-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P53396-2; Sequence=VSP_042201;
CC Name=3;
CC IsoId=P53396-3; Sequence=VSP_057230, VSP_042201;
CC -!- PTM: Phosphorylated by PKA and GSK3 in a sequential manner;
CC phosphorylation results in activation of its activity
CC (PubMed:10653665). Phosphorylation on Thr-447 and Ser-451 depends on
CC the phosphorylation state of Ser-455 (By similarity). Phosphorylation
CC on Ser-455 is decreased by prior phosphorylation on the other 2
CC residues (By similarity). {ECO:0000250|UniProtKB:P16638,
CC ECO:0000269|PubMed:10653665}.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}.
CC -!- PTM: Acetylated at Lys-540, Lys-546 and Lys-554 by KAT2B/PCAF
CC (PubMed:23932781). Acetylation is promoted by glucose and stabilizes
CC the protein, probably by preventing ubiquitination at the same sites
CC (PubMed:23932781). Acetylation promotes de novo lipid synthesis
CC (PubMed:23932781). Deacetylated by SIRT2.
CC {ECO:0000269|PubMed:23932781}.
CC -!- PTM: Ubiquitinated at Lys-540, Lys-546 and Lys-554 by UBR4, leading to
CC its degradation. Ubiquitination is probably inhibited by acetylation at
CC same site (Probable). {ECO:0000305|PubMed:23932781}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the succinate/malate
CC CoA ligase beta subunit family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the succinate/malate
CC CoA ligase alpha subunit family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ACLYID50486ch17q21.html";
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DR EMBL; X64330; CAA45614.1; -; mRNA.
DR EMBL; U18197; AAB60340.1; -; mRNA.
DR EMBL; AK295675; BAG58532.1; -; mRNA.
DR EMBL; AK304802; BAG65552.1; -; mRNA.
DR EMBL; AC091172; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC125257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006195; AAH06195.1; -; mRNA.
DR CCDS; CCDS11412.1; -. [P53396-1]
DR CCDS; CCDS11413.1; -. [P53396-2]
DR PIR; S21173; S21173.
DR RefSeq; NP_001087.2; NM_001096.2. [P53396-1]
DR RefSeq; NP_001290203.1; NM_001303274.1.
DR RefSeq; NP_001290204.1; NM_001303275.1.
DR RefSeq; NP_942127.1; NM_198830.1. [P53396-2]
DR RefSeq; XP_005257452.1; XM_005257395.1. [P53396-1]
DR PDB; 3MWD; X-ray; 2.10 A; A=1-425, B=487-820.
DR PDB; 3MWE; X-ray; 2.20 A; A=1-425, B=487-821.
DR PDB; 3PFF; X-ray; 2.30 A; A=1-817.
DR PDB; 5TDE; X-ray; 1.70 A; A=1-425, B=487-810.
DR PDB; 5TDF; X-ray; 1.80 A; A=1-425, B=487-810.
DR PDB; 5TDM; X-ray; 2.10 A; A=1-425, B=487-810.
DR PDB; 5TDZ; X-ray; 2.00 A; A=1-425, B=487-810.
DR PDB; 5TE1; X-ray; 2.25 A; A/B=1-817.
DR PDB; 5TEQ; X-ray; 2.30 A; A/B=1-817.
DR PDB; 5TES; X-ray; 2.40 A; A=1-425, B=487-810.
DR PDB; 5TET; X-ray; 2.20 A; A=1-425, B=487-810.
DR PDB; 6HXH; X-ray; 3.30 A; A/B/C/D/E/F/G/H=1-424, A/B/C/D/E/F/G/H=488-1101.
DR PDB; 6HXK; X-ray; 1.85 A; A/B/C/D=836-1101.
DR PDB; 6HXL; X-ray; 1.35 A; A/B/C/D/E/F/G/H=836-1101.
DR PDB; 6HXM; X-ray; 1.30 A; A/B=836-1101.
DR PDB; 6O0H; EM; 3.67 A; A/B/C/D=1-1101.
DR PDB; 6POE; EM; 3.50 A; A/B/C/D=1-1101.
DR PDB; 6POF; EM; 4.30 A; A/B/C/D=1-1101.
DR PDB; 6QFB; X-ray; 3.25 A; A/B/C/D=1-1101.
DR PDB; 6UI9; EM; 3.10 A; A/B/C/D=1-1101.
DR PDB; 6UIA; EM; 4.30 A; A/B/C/D=1-1101.
DR PDB; 6UUW; EM; 2.85 A; A/B/C/D=1-1101.
DR PDB; 6UUZ; EM; 3.00 A; A/B/C/D=1-1100.
DR PDB; 6UV5; EM; 3.40 A; A/B/C/D=1-1100.
DR PDB; 6Z2H; X-ray; 1.80 A; A/B/C/D=836-1101.
DR PDB; 7LIW; EM; 2.85 A; A/B/C/D=1-1101.
DR PDB; 7LJ9; EM; 3.00 A; A/B/C/D=1-1101.
DR PDB; 7LLA; EM; 2.97 A; A/B/C/D=1-1101.
DR PDBsum; 3MWD; -.
DR PDBsum; 3MWE; -.
DR PDBsum; 3PFF; -.
DR PDBsum; 5TDE; -.
DR PDBsum; 5TDF; -.
DR PDBsum; 5TDM; -.
DR PDBsum; 5TDZ; -.
DR PDBsum; 5TE1; -.
DR PDBsum; 5TEQ; -.
DR PDBsum; 5TES; -.
DR PDBsum; 5TET; -.
DR PDBsum; 6HXH; -.
DR PDBsum; 6HXK; -.
DR PDBsum; 6HXL; -.
DR PDBsum; 6HXM; -.
DR PDBsum; 6O0H; -.
DR PDBsum; 6POE; -.
DR PDBsum; 6POF; -.
DR PDBsum; 6QFB; -.
DR PDBsum; 6UI9; -.
DR PDBsum; 6UIA; -.
DR PDBsum; 6UUW; -.
DR PDBsum; 6UUZ; -.
DR PDBsum; 6UV5; -.
DR PDBsum; 6Z2H; -.
DR PDBsum; 7LIW; -.
DR PDBsum; 7LJ9; -.
DR PDBsum; 7LLA; -.
DR AlphaFoldDB; P53396; -.
DR SASBDB; P53396; -.
DR SMR; P53396; -.
DR BioGRID; 106563; 160.
DR IntAct; P53396; 53.
DR MINT; P53396; -.
DR STRING; 9606.ENSP00000253792; -.
DR BindingDB; P53396; -.
DR ChEMBL; CHEMBL3720; -.
DR DrugBank; DB11936; Bempedoic acid.
DR DrugCentral; P53396; -.
DR SwissLipids; SLP:000000779; -.
DR CarbonylDB; P53396; -.
DR GlyGen; P53396; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P53396; -.
DR MetOSite; P53396; -.
DR PhosphoSitePlus; P53396; -.
DR SwissPalm; P53396; -.
DR BioMuta; ACLY; -.
DR DMDM; 116241237; -.
DR EPD; P53396; -.
DR jPOST; P53396; -.
DR MassIVE; P53396; -.
DR MaxQB; P53396; -.
DR PaxDb; P53396; -.
DR PeptideAtlas; P53396; -.
DR PRIDE; P53396; -.
DR ProteomicsDB; 56581; -. [P53396-1]
DR ProteomicsDB; 56582; -. [P53396-2]
DR ProteomicsDB; 5912; -.
DR Antibodypedia; 3578; 565 antibodies from 37 providers.
DR DNASU; 47; -.
DR Ensembl; ENST00000352035.7; ENSP00000253792.2; ENSG00000131473.17. [P53396-1]
DR Ensembl; ENST00000353196.5; ENSP00000345398.1; ENSG00000131473.17. [P53396-2]
DR Ensembl; ENST00000393896.6; ENSP00000377474.1; ENSG00000131473.17. [P53396-2]
DR Ensembl; ENST00000537919.5; ENSP00000445349.1; ENSG00000131473.17. [P53396-3]
DR Ensembl; ENST00000590151.5; ENSP00000466259.1; ENSG00000131473.17. [P53396-1]
DR GeneID; 47; -.
DR KEGG; hsa:47; -.
DR MANE-Select; ENST00000352035.7; ENSP00000253792.2; NM_001096.3; NP_001087.2.
DR UCSC; uc002hyg.4; human. [P53396-1]
DR CTD; 47; -.
DR DisGeNET; 47; -.
DR GeneCards; ACLY; -.
DR HGNC; HGNC:115; ACLY.
DR HPA; ENSG00000131473; Low tissue specificity.
DR MIM; 108728; gene.
DR neXtProt; NX_P53396; -.
DR OpenTargets; ENSG00000131473; -.
DR PharmGKB; PA24441; -.
DR VEuPathDB; HostDB:ENSG00000131473; -.
DR eggNOG; KOG1254; Eukaryota.
DR GeneTree; ENSGT00940000154881; -.
DR HOGENOM; CLU_006587_2_0_1; -.
DR InParanoid; P53396; -.
DR OMA; ANFLCAD; -.
DR OrthoDB; 349367at2759; -.
DR PhylomeDB; P53396; -.
DR TreeFam; TF300560; -.
DR BioCyc; MetaCyc:HS05535-MON; -.
DR BRENDA; 2.3.3.8; 2681.
DR PathwayCommons; P53396; -.
DR Reactome; R-HSA-163765; ChREBP activates metabolic gene expression.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-75105; Fatty acyl-CoA biosynthesis.
DR SABIO-RK; P53396; -.
DR SignaLink; P53396; -.
DR SIGNOR; P53396; -.
DR BioGRID-ORCS; 47; 301 hits in 1083 CRISPR screens.
DR ChiTaRS; ACLY; human.
DR EvolutionaryTrace; P53396; -.
DR GenomeRNAi; 47; -.
DR Pharos; P53396; Tclin.
DR PRO; PR:P53396; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P53396; protein.
DR Bgee; ENSG00000131473; Expressed in islet of Langerhans and 210 other tissues.
DR ExpressionAtlas; P53396; baseline and differential.
DR Genevisible; P53396; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; TAS:BHF-UCL.
DR GO; GO:0003878; F:ATP citrate synthase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0006695; P:cholesterol biosynthetic process; TAS:BHF-UCL.
DR GO; GO:0006101; P:citrate metabolic process; IDA:BHF-UCL.
DR GO; GO:0015936; P:coenzyme A metabolic process; TAS:BHF-UCL.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0008610; P:lipid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IDA:BHF-UCL.
DR Gene3D; 1.10.230.10; -; 1.
DR Gene3D; 3.40.50.261; -; 2.
DR InterPro; IPR014608; ATP-citrate_synthase.
DR InterPro; IPR017440; Cit_synth/succinyl-CoA_lig_AS.
DR InterPro; IPR032263; Citrate-bd.
DR InterPro; IPR016143; Citrate_synth-like_sm_a-sub.
DR InterPro; IPR002020; Citrate_synthase.
DR InterPro; IPR036969; Citrate_synthase_sf.
DR InterPro; IPR033847; Citrt_syn/SCS-alpha_CS.
DR InterPro; IPR003781; CoA-bd.
DR InterPro; IPR005811; CoA_ligase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR017866; Succ-CoA_synthase_bsu_CS.
DR InterPro; IPR016102; Succinyl-CoA_synth-like.
DR Pfam; PF16114; Citrate_bind; 1.
DR Pfam; PF00285; Citrate_synt; 1.
DR Pfam; PF02629; CoA_binding; 1.
DR Pfam; PF00549; Ligase_CoA; 1.
DR PIRSF; PIRSF036511; ATP_citrt_syn; 1.
DR SMART; SM00881; CoA_binding; 1.
DR SUPFAM; SSF48256; SSF48256; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52210; SSF52210; 1.
DR PROSITE; PS01216; SUCCINYL_COA_LIG_1; 1.
DR PROSITE; PS00399; SUCCINYL_COA_LIG_2; 1.
DR PROSITE; PS01217; SUCCINYL_COA_LIG_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW Isopeptide bond; Lipid biosynthesis; Lipid metabolism; Magnesium;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Transferase; Ubl conjugation.
FT CHAIN 1..1101
FT /note="ATP-citrate synthase"
FT /id="PRO_0000102781"
FT DOMAIN 4..265
FT /note="ATP-grasp"
FT REGION 441..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 441..458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 760
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000250"
FT BINDING 58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 66..67
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 109..111
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 118
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 201
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 203
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 346
FT /ligand="citrate"
FT /ligand_id="ChEBI:CHEBI:16947"
FT /evidence="ECO:0000269|PubMed:20558738"
FT BINDING 348
FT /ligand="citrate"
FT /ligand_id="ChEBI:CHEBI:16947"
FT /evidence="ECO:0000269|PubMed:20558738"
FT BINDING 379
FT /ligand="citrate"
FT /ligand_id="ChEBI:CHEBI:16947"
FT /evidence="ECO:0000269|PubMed:20558738"
FT BINDING 701..721
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 718
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 752..778
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 779..789
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255"
FT MOD_RES 131
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91V92"
FT MOD_RES 447
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P16638"
FT MOD_RES 451
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16638"
FT MOD_RES 455
FT /note="Phosphoserine; by PKA and PKB/AKT1 or PKB/AKT2"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 459
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 540
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:23932781"
FT MOD_RES 546
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:23932781,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 554
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:23932781,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 639
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 663
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 682
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 839
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 948
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 968
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 978
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91V92"
FT MOD_RES 1077
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195"
FT CROSSLNK 540
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000305|PubMed:23932781"
FT CROSSLNK 546
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000305|PubMed:23932781"
FT CROSSLNK 554
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000305|PubMed:23932781"
FT VAR_SEQ 95..355
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057230"
FT VAR_SEQ 476..485
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042201"
FT VARIANT 175
FT /note="E -> D (in dbSNP:rs2304497)"
FT /evidence="ECO:0000269|PubMed:1371749,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:9116495"
FT /id="VAR_028230"
FT MUTAGEN 540
FT /note="K->R,Q: Decreased acetylation and increased de novo
FT lipid synthesis; when associated with R,Q-546 and R,Q-554."
FT /evidence="ECO:0000269|PubMed:23932781"
FT MUTAGEN 546
FT /note="K->R,Q: Decreased acetylation and increased de novo
FT lipid synthesis; when associated with R,Q-540 and R,Q-554."
FT /evidence="ECO:0000269|PubMed:23932781"
FT MUTAGEN 554
FT /note="K->R,Q: Decreased acetylation and increased de novo
FT lipid synthesis; when associated with R,Q-540 and R,Q-546."
FT /evidence="ECO:0000269|PubMed:23932781"
FT MUTAGEN 760
FT /note="H->A: Reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:1371749"
FT CONFLICT 75
FT /note="N -> D (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="V -> A (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="E -> V (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT CONFLICT 419..423
FT /note="LGHRP -> WAPA (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT CONFLICT 442..444
FT /note="SGS -> QRE (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT CONFLICT 457..459
FT /note="SES -> YESMVDEV (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT CONFLICT 653..656
FT /note="RPGS -> PQAA (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT CONFLICT 728
FT /note="C -> S (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT CONFLICT 872
FT /note="V -> A (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT CONFLICT 916..919
FT /note="AGKD -> TAVE (in Ref. 1; CAA45614)"
FT /evidence="ECO:0000305"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 8..18
FT /evidence="ECO:0007829|PDB:5TDE"
FT TURN 26..29
FT /evidence="ECO:0007829|PDB:5TEQ"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:7LLA"
FT HELIX 40..46
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:5TDE"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:7LJ9"
FT TURN 66..70
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 78..85
FT /evidence="ECO:0007829|PDB:5TDE"
FT TURN 86..90
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 118..126
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 129..136
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:3MWE"
FT HELIX 145..148
FT /evidence="ECO:0007829|PDB:3MWD"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 162..168
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:6UUW"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 178..194
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 197..208
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 226..233
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:3MWD"
FT HELIX 248..258
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 260..269
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 274..277
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:5TDZ"
FT HELIX 282..294
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 303..309
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 313..327
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:5TDZ"
FT STRAND 336..340
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 346..348
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 350..363
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 365..370
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 373..378
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 384..398
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 402..405
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 407..409
FT /evidence="ECO:0007829|PDB:6UUW"
FT HELIX 413..418
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 420..422
FT /evidence="ECO:0007829|PDB:7LJ9"
FT STRAND 427..429
FT /evidence="ECO:0007829|PDB:6UUW"
FT STRAND 499..503
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 506..518
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 525..530
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 536..543
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 546..555
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 556..562
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 568..571
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 575..585
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 593..596
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 603..616
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 619..621
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 623..625
FT /evidence="ECO:0007829|PDB:5TE1"
FT STRAND 628..630
FT /evidence="ECO:0007829|PDB:5TDE"
FT TURN 631..633
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 634..636
FT /evidence="ECO:0007829|PDB:5TDE"
FT TURN 637..640
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 643..648
FT /evidence="ECO:0007829|PDB:5TDE"
FT TURN 649..652
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 656..662
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 664..677
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 681..686
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 689..692
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 697..705
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 712..722
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 725..732
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 740..745
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 747..751
FT /evidence="ECO:0007829|PDB:5TDE"
FT STRAND 752..754
FT /evidence="ECO:0007829|PDB:5TDZ"
FT HELIX 759..762
FT /evidence="ECO:0007829|PDB:6QFB"
FT STRAND 763..765
FT /evidence="ECO:0007829|PDB:6QFB"
FT HELIX 768..770
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 772..782
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 790..792
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 793..806
FT /evidence="ECO:0007829|PDB:5TDE"
FT HELIX 825..830
FT /evidence="ECO:0007829|PDB:6UUW"
FT STRAND 833..835
FT /evidence="ECO:0007829|PDB:6UUW"
FT STRAND 839..842
FT /evidence="ECO:0007829|PDB:6HXL"
FT STRAND 844..846
FT /evidence="ECO:0007829|PDB:6HXM"
FT STRAND 848..851
FT /evidence="ECO:0007829|PDB:6HXM"
FT STRAND 853..858
FT /evidence="ECO:0007829|PDB:7LLA"
FT HELIX 859..864
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 868..878
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 884..896
FT /evidence="ECO:0007829|PDB:6HXM"
FT STRAND 902..904
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 905..915
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 920..928
FT /evidence="ECO:0007829|PDB:6HXM"
FT TURN 933..935
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 939..952
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 956..966
FT /evidence="ECO:0007829|PDB:6HXM"
FT STRAND 980..982
FT /evidence="ECO:0007829|PDB:6UUW"
FT HELIX 985..997
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 1002..1017
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 1025..1039
FT /evidence="ECO:0007829|PDB:6HXM"
FT STRAND 1040..1043
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 1045..1054
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 1056..1078
FT /evidence="ECO:0007829|PDB:6HXM"
FT HELIX 1088..1090
FT /evidence="ECO:0007829|PDB:6HXM"
FT STRAND 1091..1093
FT /evidence="ECO:0007829|PDB:6HXL"
SQ SEQUENCE 1101 AA; 120839 MW; 12BB4416A30DC30C CRC64;
MSAKAISEQT GKELLYKFIC TTSAIQNRFK YARVTPDTDW ARLLQDHPWL LSQNLVVKPD
QLIKRRGKLG LVGVNLTLDG VKSWLKPRLG QEATVGKATG FLKNFLIEPF VPHSQAEEFY
VCIYATREGD YVLFHHEGGV DVGDVDAKAQ KLLVGVDEKL NPEDIKKHLL VHAPEDKKEI
LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYVLDLAAK VDATADYICK VKWGDIEFPP
PFGREAYPEE AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE
LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV AATFKGIVRA
IRDYQGPLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI PIHVFGTETH MTAIVGMALG
HRPIPNQPPT AAHTANFLLN ASGSTSTPAP SRTASFSESR ADEVAPAKKA KPAMPQDSVP
SPRSLQGKST TLFSRHTKAI VWGMQTRAVQ GMLDFDYVCS RDEPSVAAMV YPFTGDHKQK
FYWGHKEILI PVFKNMADAM RKHPEVDVLI NFASLRSAYD STMETMNYAQ IRTIAIIAEG
IPEALTRKLI KKADQKGVTI IGPATVGGIK PGCFKIGNTG GMLDNILASK LYRPGSVAYV
SRSGGMSNEL NNIISRTTDG VYEGVAIGGD RYPGSTFMDH VLRYQDTPGV KMIVVLGEIG
GTEEYKICRG IKEGRLTKPI VCWCIGTCAT MFSSEVQFGH AGACANQASE TAVAKNQALK
EAGVFVPRSF DELGEIIQSV YEDLVANGVI VPAQEVPPPT VPMDYSWARE LGLIRKPASF
MTSICDERGQ ELIYAGMPIT EVFKEEMGIG GVLGLLWFQK RLPKYSCQFI EMCLMVTADH
GPAVSGAHNT IICARAGKDL VSSLTSGLLT IGDRFGGALD AAAKMFSKAF DSGIIPMEFV
NKMKKEGKLI MGIGHRVKSI NNPDMRVQIL KDYVRQHFPA TPLLDYALEV EKITTSKKPN
LILNVDGLIG VAFVDMLRNC GSFTREEADE YIDIGALNGI FVLGRSMGFI GHYLDQKRLK
QGLYRHPWDD ISYVLPEHMS M
