CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008694
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 ATP-citrate synthase 
Protein Synonyms/Alias
 ATP-citrate (pro-S-)-lyase; ACL; Citrate cleavage enzyme 
Gene Name
 ACLY 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
4****MSAKAISEQTGubiquitination[1]
12AISEQTGKELLYKFIubiquitination[2]
58LSQNLVVKPDQLIKRubiquitination[2, 3, 4, 5]
64VKPDQLIKRRGKLGLubiquitination[2, 4]
68QLIKRRGKLGLVGVNubiquitination[2, 4, 6]
82NLTLDGVKSWLKPRLubiquitination[4]
86DGVKSWLKPRLGQEAacetylation[7]
86DGVKSWLKPRLGQEAubiquitination[3, 4]
97GQEATVGKATGFLKNubiquitination[1, 3, 4, 5, 6]
148DVGDVDAKAQKLLVGubiquitination[3, 4, 5, 8]
151DVDAKAQKLLVGVDEacetylation[8]
151DVDAKAQKLLVGVDEubiquitination[2, 3, 5]
159LLVGVDEKLNPEDIKacetylation[8]
159LLVGVDEKLNPEDIKubiquitination[3, 4]
166KLNPEDIKKHLLVHAubiquitination[4]
167LNPEDIKKHLLVHAPubiquitination[4]
220YVLDLAAKVDATADYubiquitination[3]
230ATADYICKVKWGDIEubiquitination[2, 4, 8]
232ADYICKVKWGDIEFPubiquitination[2, 4]
259YIADLDAKSGASLKLacetylation[8, 9]
259YIADLDAKSGASLKLubiquitination[3, 4, 5, 8]
265AKSGASLKLTLLNPKubiquitination[3, 4, 8]
272KLTLLNPKGRIWTMVubiquitination[1, 2, 3, 4, 8]
369RDYQGPLKEHEVTIFubiquitination[3, 4]
468ADEVAPAKKAKPAMPubiquitination[3, 10]
469DEVAPAKKAKPAMPQubiquitination[4, 8]
471VAPAKKAKPAMPQDSubiquitination[3, 4, 8]
488SPRSLQGKSTTLFSRubiquitination[1, 2, 3, 4, 5, 6, 8, 10, 11]
498TLFSRHTKAIVWGMQubiquitination[2, 4, 5, 6]
538YPFTGDHKQKFYWGHubiquitination[3, 5]
540FTGDHKQKFYWGHKEubiquitination[4]
546QKFYWGHKEILIPVFacetylation[7]
546QKFYWGHKEILIPVFubiquitination[1, 2, 4, 5, 6]
554EILIPVFKNMADAMRacetylation[7]
554EILIPVFKNMADAMRubiquitination[4]
562NMADAMRKHPEVDVLubiquitination[4]
630PATVGGIKPGCFKIGubiquitination[1, 2]
650LDNILASKLYRPGSVubiquitination[1, 3, 5]
732YKICRGIKEGRLTKPubiquitination[10]
780VAKNQALKEAGVFVPubiquitination[1, 3, 4, 5, 10]
836RELGLIRKPASFMTSubiquitination[4, 5]
918IICARAGKDLVSSLTubiquitination[3, 5]
944GALDAAAKMFSKAFDubiquitination[2, 3]
948AAAKMFSKAFDSGIIacetylation[7]
948AAAKMFSKAFDSGIIubiquitination[2]
962IPMEFVNKMKKEGKLacetylation[7]
962IPMEFVNKMKKEGKLubiquitination[2, 3, 5]
964MEFVNKMKKEGKLIMubiquitination[4]
968NKMKKEGKLIMGIGHacetylation[7]
968NKMKKEGKLIMGIGHubiquitination[4]
978MGIGHRVKSINNPDMacetylation[7]
978MGIGHRVKSINNPDMubiquitination[4]
991DMRVQILKDYVRQHFubiquitination[1, 2, 4, 5, 6]
1077IGHYLDQKRLKQGLYacetylation[7]
1077IGHYLDQKRLKQGLYubiquitination[2, 3, 4, 6]
1080YLDQKRLKQGLYRHPubiquitination[2, 3, 4]
Reference
 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [8] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [10] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [11] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 ATP citrate-lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Has a central role in de novo lipid synthesis. In nervous tissue it may be involved in the biosynthesis of acetylcholine. 
Sequence Annotation
 NP_BIND 701 721 ATP (By similarity).
 NP_BIND 752 778 ATP (By similarity).
 REGION 779 789 CoA-binding (Potential).
 ACT_SITE 760 760 Tele-phosphohistidine intermediate (By
 METAL 718 718 Magnesium (By similarity).
 BINDING 346 346 Citrate; via amide nitrogen.
 BINDING 348 348 Citrate.
 BINDING 379 379 Citrate.
 MOD_RES 131 131 Phosphotyrosine.
 MOD_RES 447 447 Phosphothreonine (By similarity).
 MOD_RES 451 451 Phosphoserine (By similarity).
 MOD_RES 455 455 Phosphoserine; by PKA and PKB/AKT1 or
 MOD_RES 481 481 Phosphoserine.
 MOD_RES 546 546 N6-acetyllysine.
 MOD_RES 554 554 N6-acetyllysine.
 MOD_RES 639 639 Phosphothreonine.
 MOD_RES 663 663 Phosphoserine.
 MOD_RES 682 682 Phosphotyrosine.
 MOD_RES 839 839 Phosphoserine.
 MOD_RES 948 948 N6-acetyllysine.
 MOD_RES 968 968 N6-acetyllysine.
 MOD_RES 1077 1077 N6-acetyllysine.
 MOD_RES 1100 1100 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1101 AA 
Protein Sequence
MSAKAISEQT GKELLYKFIC TTSAIQNRFK YARVTPDTDW ARLLQDHPWL LSQNLVVKPD 60
QLIKRRGKLG LVGVNLTLDG VKSWLKPRLG QEATVGKATG FLKNFLIEPF VPHSQAEEFY 120
VCIYATREGD YVLFHHEGGV DVGDVDAKAQ KLLVGVDEKL NPEDIKKHLL VHAPEDKKEI 180
LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYVLDLAAK VDATADYICK VKWGDIEFPP 240
PFGREAYPEE AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE 300
LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV AATFKGIVRA 360
IRDYQGPLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI PIHVFGTETH MTAIVGMALG 420
HRPIPNQPPT AAHTANFLLN ASGSTSTPAP SRTASFSESR ADEVAPAKKA KPAMPQDSVP 480
SPRSLQGKST TLFSRHTKAI VWGMQTRAVQ GMLDFDYVCS RDEPSVAAMV YPFTGDHKQK 540
FYWGHKEILI PVFKNMADAM RKHPEVDVLI NFASLRSAYD STMETMNYAQ IRTIAIIAEG 600
IPEALTRKLI KKADQKGVTI IGPATVGGIK PGCFKIGNTG GMLDNILASK LYRPGSVAYV 660
SRSGGMSNEL NNIISRTTDG VYEGVAIGGD RYPGSTFMDH VLRYQDTPGV KMIVVLGEIG 720
GTEEYKICRG IKEGRLTKPI VCWCIGTCAT MFSSEVQFGH AGACANQASE TAVAKNQALK 780
EAGVFVPRSF DELGEIIQSV YEDLVANGVI VPAQEVPPPT VPMDYSWARE LGLIRKPASF 840
MTSICDERGQ ELIYAGMPIT EVFKEEMGIG GVLGLLWFQK RLPKYSCQFI EMCLMVTADH 900
GPAVSGAHNT IICARAGKDL VSSLTSGLLT IGDRFGGALD AAAKMFSKAF DSGIIPMEFV 960
NKMKKEGKLI MGIGHRVKSI NNPDMRVQIL KDYVRQHFPA TPLLDYALEV EKITTSKKPN 1020
LILNVDGLIG VAFVDMLRNC GSFTREEADE YIDIGALNGI FVLGRSMGFI GHYLDQKRLK 1080
QGLYRHPWDD ISYVLPEHMS M 1101 
Gene Ontology
 GO:0009346; C:citrate lyase complex; TAS:ProtInc.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003878; F:ATP citrate synthase activity; TAS:Reactome.
 GO:0048037; F:cofactor binding; IEA:InterPro.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004775; F:succinate-CoA ligase (ADP-forming) activity; IEA:InterPro.
 GO:0006200; P:ATP catabolic process; TAS:ProtInc.
 GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
 GO:0006101; P:citrate metabolic process; TAS:ProtInc.
 GO:0015936; P:coenzyme A metabolic process; TAS:ProtInc.
 GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
 GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
 GO:0031325; P:positive regulation of cellular metabolic process; TAS:Reactome.
 GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome. 
Interpro
 IPR014608; ATP-citrate_synthase.
 IPR013650; ATP-grasp_succ-CoA_synth-type.
 IPR013816; ATP_grasp_subdomain_2.
 IPR017440; Cit_synth/succinyl-CoA_lig_AS.
 IPR016143; Citrate_synth-like_sm_a-sub.
 IPR002020; Citrate_synthase-like.
 IPR016141; Citrate_synthase-like_core.
 IPR003781; CoA-bd.
 IPR005810; CoA_lig_alpha.
 IPR005811; CoA_ligase.
 IPR016040; NAD(P)-bd_dom.
 IPR017866; Succ-CoA_synthase_bsu_CS.
 IPR016102; Succinyl-CoA_synth-like. 
Pfam
 PF08442; ATP-grasp_2
 PF00285; Citrate_synt
 PF02629; CoA_binding
 PF00549; Ligase_CoA 
SMART
  
PROSITE
 PS01216; SUCCINYL_COA_LIG_1
 PS00399; SUCCINYL_COA_LIG_2
 PS01217; SUCCINYL_COA_LIG_3 
PRINTS