CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002846
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Leukotriene A-4 hydrolase 
Protein Synonyms/Alias
 LTA-4 hydrolase; Leukotriene A(4) hydrolase 
Gene Name
 LTA4H 
Gene Synonyms/Alias
 LTA4 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
20PASVCRTKHLHLRCSubiquitination[1, 2, 3]
58RSLVLDTKDLTIEKVubiquitination[4]
64TKDLTIEKVVINGQEubiquitination[4]
73VINGQEVKYALGERQacetylation[5]
73VINGQEVKYALGERQubiquitination[1, 3, 4, 6, 7, 8, 9]
83LGERQSYKGSPMEISubiquitination[4, 8]
127TPEQTSGKEHPYLFSubiquitination[4]
154CQDTPSVKLTYTAEVubiquitination[4]
188DPEDPSRKIYKFIQKubiquitination[4]
191DPSRKIYKFIQKVPIubiquitination[4]
195KIYKFIQKVPIPCYLacetylation[10]
225RTLVWSEKEQVEKSAubiquitination[4, 6, 8]
230SEKEQVEKSAYEFSEubiquitination[4, 6, 11]
337CGRLFGEKFRHFNALacetylation[5]
337CGRLFGEKFRHFNALubiquitination[4, 12]
355GELQNSVKTFGETHPubiquitination[4, 11, 13]
414FLKAYVEKFSYKSITacetylation[5, 14]
414FLKAYVEKFSYKSITubiquitination[1, 3]
418YVEKFSYKSITTDDWacetylation[14]
418YVEKFSYKSITTDDWubiquitination[1, 3, 6, 9, 11, 13]
480SQRWITAKEDDLNSFubiquitination[1, 3, 4, 6, 11]
493SFNATDLKDLSSHQLubiquitination[12, 13]
519PLPLGHIKRMQEVYNubiquitination[4, 8, 9, 12]
557DAIPLALKMATEQGRubiquitination[4, 6]
566ATEQGRMKFTRPLFKubiquitination[4]
573KFTRPLFKDLAAFDKacetylation[5, 12]
573KFTRPLFKDLAAFDKubiquitination[1, 3, 4, 12]
580KDLAAFDKSHDQAVRubiquitination[4]
593VRTYQEHKASMHPVTubiquitination[1, 3, 4]
606VTAMLVGKDLKVD**ubiquitination[4]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [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] 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]
 [6] 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]
 [7] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [8] 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]
 [9] 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]
 [10] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [11] 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]
 [12] 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]
 [13] 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]
 [14] 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
Functional Description
 Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity. 
Sequence Annotation
 REGION 135 137 Substrate binding.
 REGION 267 272 Substrate binding.
 REGION 564 566 Substrate binding.
 ACT_SITE 297 297 Proton acceptor (Probable).
 ACT_SITE 384 384 Proton donor (Probable).
 METAL 296 296 Zinc; catalytic.
 METAL 300 300 Zinc; catalytic.
 METAL 319 319 Zinc; catalytic.
 MOD_RES 73 73 N6-acetyllysine.
 MOD_RES 337 337 N6-acetyllysine.
 MOD_RES 414 414 N6-acetyllysine.
 MOD_RES 416 416 Phosphoserine.
 MOD_RES 573 573 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase; Leukotriene biosynthesis; Metal-binding; Metalloprotease; Phosphoprotein; Polymorphism; Protease; Reference proteome; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 611 AA 
Protein Sequence
MPEIVDTCSL ASPASVCRTK HLHLRCSVDF TRRTLTGTAA LTVQSQEDNL RSLVLDTKDL 60
TIEKVVINGQ EVKYALGERQ SYKGSPMEIS LPIALSKNQE IVIEISFETS PKSSALQWLT 120
PEQTSGKEHP YLFSQCQAIH CRAILPCQDT PSVKLTYTAE VSVPKELVAL MSAIRDGETP 180
DPEDPSRKIY KFIQKVPIPC YLIALVVGAL ESRQIGPRTL VWSEKEQVEK SAYEFSETES 240
MLKIAEDLGG PYVWGQYDLL VLPPSFPYGG MENPCLTFVT PTLLAGDKSL SNVIAHEISH 300
SWTGNLVTNK TWDHFWLNEG HTVYLERHIC GRLFGEKFRH FNALGGWGEL QNSVKTFGET 360
HPFTKLVVDL TDIDPDVAYS SVPYEKGFAL LFYLEQLLGG PEIFLGFLKA YVEKFSYKSI 420
TTDDWKDFLY SYFKDKVDVL NQVDWNAWLY SPGLPPIKPN YDMTLTNACI ALSQRWITAK 480
EDDLNSFNAT DLKDLSSHQL NEFLAQTLQR APLPLGHIKR MQEVYNFNAI NNSEIRFRWL 540
RLCIQSKWED AIPLALKMAT EQGRMKFTRP LFKDLAAFDK SHDQAVRTYQ EHKASMHPVT 600
AMLVGKDLKV D 611 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0004177; F:aminopeptidase activity; IDA:UniProtKB.
 GO:0004301; F:epoxide hydrolase activity; IDA:UniProtKB.
 GO:0004463; F:leukotriene-A4 hydrolase activity; IDA:UniProtKB.
 GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
 GO:0006954; P:inflammatory response; NAS:ProtInc.
 GO:0019370; P:leukotriene biosynthetic process; IDA:UniProtKB.
 GO:0043171; P:peptide catabolic process; IDA:UniProtKB.
 GO:0006508; P:proteolysis; IEA:UniProtKB-KW. 
Interpro
 IPR016024; ARM-type_fold.
 IPR012777; Leukotriene_A4_hydrolase.
 IPR001930; Peptidase_M1.
 IPR015211; Peptidase_M1_C.
 IPR014782; Peptidase_M1_N. 
Pfam
 PF09127; Leuk-A4-hydro_C
 PF01433; Peptidase_M1 
SMART
  
PROSITE
 PS00142; ZINC_PROTEASE 
PRINTS
 PR00756; ALADIPTASE.