CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006397
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Bifunctional epoxide hydrolase 2 
Protein Synonyms/Alias
 Cytosolic epoxide hydrolase 2; CEH; Epoxide hydratase; Soluble epoxide hydrolase; SEH; Lipid-phosphate phosphatase 
Gene Name
 Ephx2 
Gene Synonyms/Alias
 Eph2 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
55GPTEQLMKGKITFSQacetylation[1]
55GPTEQLMKGKITFSQsuccinylation[1]
55GPTEQLMKGKITFSQubiquitination[2]
57TEQLMKGKITFSQWVacetylation[1]
57TEQLMKGKITFSQWVsuccinylation[1]
57TEQLMKGKITFSQWVubiquitination[2]
76ESYRKSSKACGANLPubiquitination[2]
132NWLDDGDKRDSLAQMacetylation[3, 4]
176LLDTLKAKPNEVVFLacetylation[1, 3, 4, 5]
176LLDTLKAKPNEVVFLsuccinylation[1]
176LLDTLKAKPNEVVFLubiquitination[2]
191DDFGSNLKPARDMGMacetylation[3, 4, 5, 6]
191DDFGSNLKPARDMGMubiquitination[2]
215SALRELEKVTGTQFPacetylation[3, 4, 5, 6, 7]
215SALRELEKVTGTQFPubiquitination[2]
243SHGYVTVKPGIRLHFacetylation[3]
243SHGYVTVKPGIRLHFubiquitination[2]
371DPDVSPMKVIRSIPVacetylation[1]
371DPDVSPMKVIRSIPVsuccinylation[1]
371DPDVSPMKVIRSIPVubiquitination[2]
397VAEAELEKNMSRTFKubiquitination[2]
404KNMSRTFKSFFRASDubiquitination[2]
420TGFIAVHKATEIGGIacetylation[1, 3]
420TGFIAVHKATEIGGIsuccinylation[1]
420TGFIAVHKATEIGGIubiquitination[2]
454EFYIQQFKKTGFRGPacetylation[1, 6]
454EFYIQQFKKTGFRGPsuccinylation[1]
454EFYIQQFKKTGFRGPubiquitination[2]
473RNTERNWKWSCKGLGacetylation[3, 4, 5]
473RNTERNWKWSCKGLGubiquitination[2]
477RNWKWSCKGLGRKILacetylation[4]
477RNWKWSCKGLGRKILubiquitination[2]
482SCKGLGRKILVPALMubiquitination[2]
504VLRPEMSKNMEKWIPacetylation[1, 3, 4, 6, 7]
504VLRPEMSKNMEKWIPsuccinylation[1]
504VLRPEMSKNMEKWIPubiquitination[2]
508EMSKNMEKWIPFLKRacetylation[1, 3, 4, 5, 6]
508EMSKNMEKWIPFLKRsuccinylation[1]
508EMSKNMEKWIPFLKRubiquitination[2]
514EKWIPFLKRGHIEDCubiquitination[2]
553QNPSVTSKI******acetylation[1]
553QNPSVTSKI******succinylation[1]
553QNPSVTSKI******ubiquitination[2]
Reference
 [1] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [2] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [3] Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.
 Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ.
 Mol Cell. 2013 Jan 10;49(1):186-99. [PMID: 23201123]
 [4] Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.
 Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ.
 J Biol Chem. 2013 Jul 17;. [PMID: 23864654]
 [5] Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways.
 Rardin MJ, Newman JC, Held JM, Cusack MP, Sorensen DJ, Li B, Schilling B, Mooney SD, Kahn CR, Verdin E, Gibson BW.
 Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6601-6. [PMID: 23576753]
 [6] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
 Simon GM, Cheng J, Gordon JI.
 Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]
 [7] Circadian acetylome reveals regulation of mitochondrial metabolic pathways.
 Masri S, Patel VR, Eckel-Mahan KL, Peleg S, Forne I, Ladurner AG, Baldi P, Imhof A, Sassone-Corsi P.
 Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3339-44. [PMID: 23341599] 
Functional Description
 Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo- 9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro- 9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy- octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate (By similarity). 
Sequence Annotation
 REGION 1 224 Phosphatase.
 REGION 123 124 Phosphate binding (By similarity).
 REGION 233 554 Epoxide hydrolase.
 MOTIF 552 554 Microbody targeting signal (Potential).
 ACT_SITE 333 333 Nucleophile.
 ACT_SITE 465 465 Proton donor.
 ACT_SITE 523 523 Proton acceptor.
 METAL 9 9 Magnesium (By similarity).
 METAL 11 11 Magnesium (By similarity).
 METAL 185 185 Magnesium (By similarity).
 BINDING 381 381 Substrate (By similarity).
 LIPID 521 521 S-(15-deoxy-Delta12,14-prostaglandin J2-  
Keyword
 3D-structure; Alternative splicing; Aromatic hydrocarbons catabolism; Complete proteome; Cytoplasm; Detoxification; Direct protein sequencing; Hydrolase; Lipid metabolism; Lipoprotein; Magnesium; Metal-binding; Multifunctional enzyme; Peroxisome; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 554 AA 
Protein Sequence
MALRVAAFDL DGVLALPSIA GAFRRSEEAL ALPRDFLLGA YQTEFPEGPT EQLMKGKITF 60
SQWVPLMDES YRKSSKACGA NLPENFSISQ IFSQAMAARS INRPMLQAAI ALKKKGFTTC 120
IVTNNWLDDG DKRDSLAQMM CELSQHFDFL IESCQVGMIK PEPQIYNFLL DTLKAKPNEV 180
VFLDDFGSNL KPARDMGMVT ILVHNTASAL RELEKVTGTQ FPEAPLPVPC NPNDVSHGYV 240
TVKPGIRLHF VEMGSGPALC LCHGFPESWF SWRYQIPALA QAGFRVLAID MKGYGDSSSP 300
PEIEEYAMEL LCKEMVTFLD KLGIPQAVFI GHDWAGVMVW NMALFYPERV RAVASLNTPF 360
MPPDPDVSPM KVIRSIPVFN YQLYFQEPGV AEAELEKNMS RTFKSFFRAS DETGFIAVHK 420
ATEIGGILVN TPEDPNLSKI TTEEEIEFYI QQFKKTGFRG PLNWYRNTER NWKWSCKGLG 480
RKILVPALMV TAEKDIVLRP EMSKNMEKWI PFLKRGHIED CGHWTQIEKP TEVNQILIKW 540
LQTEVQNPSV TSKI 554 
Gene Ontology
 GO:0005925; C:focal adhesion; IEA:Compara.
 GO:0005794; C:Golgi apparatus; IEA:Compara.
 GO:0005730; C:nucleolus; IEA:Compara.
 GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
 GO:0033885; F:10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity; IEA:EC.
 GO:0003869; F:4-nitrophenylphosphatase activity; IEA:Compara.
 GO:0004301; F:epoxide hydrolase activity; IEA:EC.
 GO:0042577; F:lipid phosphatase activity; ISS:UniProtKB.
 GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
 GO:0015643; F:toxic substance binding; IEA:Compara.
 GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
 GO:0046839; P:phospholipid dephosphorylation; ISS:UniProtKB.
 GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
 GO:0090181; P:regulation of cholesterol metabolic process; IMP:UniProtKB.
 GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
 GO:0046272; P:stilbene catabolic process; IEA:Compara. 
Interpro
 IPR000073; AB_hydrolase_1.
 IPR000639; Epox_hydrolase-like.
 IPR023214; HAD-like_dom.
 IPR006402; HAD-SF_hydro_IA_v3.
 IPR023198; PGP_dom2. 
Pfam
 PF00561; Abhydrolase_1
 PF13419; HAD_2 
SMART
  
PROSITE
  
PRINTS
 PR00111; ABHYDROLASE.
 PR00412; EPOXHYDRLASE.