CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000944
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Long-chain-fatty-acid--CoA ligase 4 
Protein Synonyms/Alias
 Long-chain acyl-CoA synthetase 4; LACS 4 
Gene Name
 ACSL4 
Gene Synonyms/Alias
 ACS4; FACL4; LACS4 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
49MAKRIKAKPTSDKPGubiquitination[1]
54KAKPTSDKPGSPYRSubiquitination[1]
89LFDHAVSKFGKKDSLacetylation[2]
113NEMQPNGKVFKKLILubiquitination[1, 3]
148GLTALGLKPKNTIAIubiquitination[4, 5]
231HIIYVDNKAINKAEYubiquitination[4, 6]
354TLSDQSSKIKKGSKGubiquitination[1, 4, 6, 7]
367KGDCTVLKPTLMAAVubiquitination[1]
383EIMDRIYKNVMSKVQubiquitination[1, 6]
388IYKNVMSKVQEMNYIubiquitination[3, 4, 5, 6]
397QEMNYIQKTLFKIGYacetylation[8]
397QEMNYIQKTLFKIGYubiquitination[3]
401YIQKTLFKIGYDYKLacetylation[8]
401YIQKTLFKIGYDYKLubiquitination[1, 3, 4, 5, 6, 7]
427CNLLLFKKVKALLGGubiquitination[1]
498PLICCEIKLKDWQEGubiquitination[1, 9]
500ICCEIKLKDWQEGGYubiquitination[1, 3, 4, 5]
512GGYTINDKPNPRGEIubiquitination[1]
536GYFKNEEKTAEDYSVubiquitination[4, 7]
587GEYVSLGKVEAALKNubiquitination[1, 4]
593GKVEAALKNCPLIDNubiquitination[1]
621SFVVPNQKRLTLLAQubiquitination[1, 3, 4, 5, 6, 7, 10, 11]
651AMEAEILKEIREAANubiquitination[6, 7]
661REAANAMKLERFEIPubiquitination[1, 4, 5, 6, 7]
670ERFEIPIKVRLSPEPubiquitination[1, 3, 4, 5, 6, 7, 10, 11]
690GLVTDAFKLKRKELRubiquitination[1, 4, 6]
692VTDAFKLKRKELRNHubiquitination[1]
702ELRNHYLKDIERMYGubiquitination[1, 3, 5, 6, 7, 10, 11]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [9] 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]
 [10] 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]
 [11] 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] 
Functional Description
 Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses arachidonate and eicosapentaenoate as substrates. 
Sequence Annotation
  
Keyword
 Alport syndrome; Alternative splicing; ATP-binding; Complete proteome; Deafness; Disease mutation; Elliptocytosis; Endoplasmic reticulum; Fatty acid metabolism; Hereditary hemolytic anemia; Ligase; Lipid metabolism; Magnesium; Membrane; Mental retardation; Microsome; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding; Peroxisome; Polymorphism; Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 711 AA 
Protein Sequence
MKLKLNVLTI ILLPVHLLIT IYSALIFIPW YFLTNAKKKN AMAKRIKAKP TSDKPGSPYR 60
SVTHFDSLAV IDIPGADTLD KLFDHAVSKF GKKDSLGTRE ILSEENEMQP NGKVFKKLIL 120
GNYKWMNYLE VNRRVNNFGS GLTALGLKPK NTIAIFCETR AEWMIAAQTC FKYNFPLVTL 180
YATLGKEAVV HGLNESEASY LITSVELLES KLKTALLDIS CVKHIIYVDN KAINKAEYPE 240
GFEIHSMQSV EELGSNPENL GIPPSRPTPS DMAIVMYTSG STGRPKGVMM HHSNLIAGMT 300
GQCERIPGLG PKDTYIGYLP LAHVLELTAE ISCFTYGCRI GYSSPLTLSD QSSKIKKGSK 360
GDCTVLKPTL MAAVPEIMDR IYKNVMSKVQ EMNYIQKTLF KIGYDYKLEQ IKKGYDAPLC 420
NLLLFKKVKA LLGGNVRMML SGGAPLSPQT HRFMNVCFCC PIGQGYGLTE SCGAGTVTEV 480
TDYTTGRVGA PLICCEIKLK DWQEGGYTIN DKPNPRGEIV IGGQNISMGY FKNEEKTAED 540
YSVDENGQRW FCTGDIGEFH PDGCLQIIDR KKDLVKLQAG EYVSLGKVEA ALKNCPLIDN 600
ICAFAKSDQS YVISFVVPNQ KRLTLLAQQK GVEGTWVDIC NNPAMEAEIL KEIREAANAM 660
KLERFEIPIK VRLSPEPWTP ETGLVTDAFK LKRKELRNHY LKDIERMYGG K 711 
Gene Ontology
 GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0005811; C:lipid particle; IDA:UniProtKB.
 GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
 GO:0047676; F:arachidonate-CoA ligase activity; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:MGI.
 GO:0031957; F:very long-chain fatty acid-CoA ligase activity; IMP:UniProtKB.
 GO:0060996; P:dendritic spine development; IEA:Compara.
 GO:0060136; P:embryonic process involved in female pregnancy; IEA:Compara.
 GO:0015908; P:fatty acid transport; IEA:Compara.
 GO:0008610; P:lipid biosynthetic process; IDA:UniProtKB.
 GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
 GO:0032307; P:negative regulation of prostaglandin secretion; IDA:UniProtKB.
 GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
 GO:0070672; P:response to interleukin-15; IEA:Compara.
 GO:0007584; P:response to nutrient; IEA:Compara.
 GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome. 
Interpro
 IPR020845; AMP-binding_CS.
 IPR000873; AMP-dep_Synth/Lig. 
Pfam
 PF00501; AMP-binding 
SMART
  
PROSITE
 PS00455; AMP_BINDING 
PRINTS