CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007430
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Trifunctional enzyme subunit alpha, mitochondrial 
Protein Synonyms/Alias
 78 kDa gastrin-binding protein; TP-alpha; Long-chain enoyl-CoA hydratase; Long chain 3-hydroxyacyl-CoA dehydrogenase 
Gene Name
 HADHA 
Gene Synonyms/Alias
 HADH 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
60RINSPNSKVNTLSKEubiquitination[1, 2, 3]
129EAQRIVEKLEKSTKPacetylation[4]
166RIATKDRKTVLGTPEubiquitination[1]
214IRADRAKKMGLVDQLubiquitination[1]
230EPLGPGLKPPEERTIubiquitination[2]
295EKVRKQTKGLYPAPLacetylation[4]
303GLYPAPLKIIDVVKTacetylation[4]
303GLYPAPLKIIDVVKTubiquitination[1, 2, 5]
309LKIIDVVKTGIEQGSubiquitination[1, 6]
326GYLCESQKFGELVMTacetylation[4, 7]
334FGELVMTKESKALMGubiquitination[1, 2]
350YHGQVLCKKNKFGAPacetylation[3]
353QVLCKKNKFGAPQKDacetylation[4]
359NKFGAPQKDVKHLAIacetylation[4]
359NKFGAPQKDVKHLAIubiquitination[1]
390KGLKTILKDATLTALacetylation[8]
406RGQQQVFKGLNDKVKacetylation[3, 4, 7, 8, 9]
411VFKGLNDKVKKKALTacetylation[3, 7]
455VFEDLSLKHRVLKEVubiquitination[6]
493AVSKRPEKVIGMHYFubiquitination[2]
505HYFSPVDKMQLLEIIacetylation[4, 7, 9]
519ITTEKTSKDTSASAVubiquitination[1]
540GKVIIVVKDGPGFYTacetylation[4]
569LQEGVDPKKLDSLTTacetylation[4]
605HVAEDLGKVFGERFGubiquitination[2]
625LLTQMVSKGFLGRKSubiquitination[1, 2, 10]
634FLGRKSGKGFYIYQEubiquitination[2]
644YIYQEGVKRKDLNSDacetylation[4]
644YIYQEGVKRKDLNSDubiquitination[2]
646YQEGVKRKDLNSDMDubiquitination[2]
728VDLYGAQKIVDRLKKubiquitination[1, 2, 10]
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] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [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] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [10] 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] 
Functional Description
 Bifunctional subunit. 
Sequence Annotation
 MOD_RES 129 129 N6-acetyllysine (By similarity).
 MOD_RES 295 295 N6-acetyllysine.
 MOD_RES 303 303 N6-acetyllysine.
 MOD_RES 326 326 N6-acetyllysine (By similarity).
 MOD_RES 350 350 N6-acetyllysine (By similarity).
 MOD_RES 406 406 N6-acetyllysine.
 MOD_RES 505 505 N6-acetyllysine.
 MOD_RES 540 540 N6-acetyllysine.
 MOD_RES 569 569 N6-acetyllysine (By similarity).
 MOD_RES 644 644 N6-acetyllysine.
 MOD_RES 728 728 N6-acetyllysine (By similarity).  
Keyword
 Acetylation; Complete proteome; Disease mutation; Fatty acid metabolism; Lipid metabolism; Lyase; Mitochondrion; Multifunctional enzyme; NAD; Oxidoreductase; Polymorphism; Reference proteome; Transit peptide. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 763 AA 
Protein Sequence
MVACRAIGIL SRFSAFRILR SRGYICRNFT GSSALLTRTH INYGVKGDVA VVRINSPNSK 60
VNTLSKELHS EFSEVMNEIW ASDQIRSAVL ISSKPGCFIA GADINMLAAC KTLQEVTQLS 120
QEAQRIVEKL EKSTKPIVAA INGSCLGGGL EVAISCQYRI ATKDRKTVLG TPEVLLGALP 180
GAGGTQRLPK MVGVPAALDM MLTGRSIRAD RAKKMGLVDQ LVEPLGPGLK PPEERTIEYL 240
EEVAITFAKG LADKKISPKR DKGLVEKLTA YAMTIPFVRQ QVYKKVEEKV RKQTKGLYPA 300
PLKIIDVVKT GIEQGSDAGY LCESQKFGEL VMTKESKALM GLYHGQVLCK KNKFGAPQKD 360
VKHLAILGAG LMGAGIAQVS VDKGLKTILK DATLTALDRG QQQVFKGLND KVKKKALTSF 420
ERDSIFSNLT GQLDYQGFEK ADMVIEAVFE DLSLKHRVLK EVEAVIPDHC IFASNTSALP 480
ISEIAAVSKR PEKVIGMHYF SPVDKMQLLE IITTEKTSKD TSASAVAVGL KQGKVIIVVK 540
DGPGFYTTRC LAPMMSEVIR ILQEGVDPKK LDSLTTSFGF PVGAATLVDE VGVDVAKHVA 600
EDLGKVFGER FGGGNPELLT QMVSKGFLGR KSGKGFYIYQ EGVKRKDLNS DMDSILASLK 660
LPPKSEVSSD EDIQFRLVTR FVNEAVMCLQ EGILATPAEG DIGAVFGLGF PPCLGGPFRF 720
VDLYGAQKIV DRLKKYEAAY GKQFTPCQLL ADHANSPNKK FYQ 763 
Gene Ontology
 GO:0016507; C:mitochondrial fatty acid beta-oxidation multienzyme complex; IEA:Compara.
 GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
 GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; TAS:ProtInc.
 GO:0003985; F:acetyl-CoA C-acetyltransferase activity; TAS:ProtInc.
 GO:0004300; F:enoyl-CoA hydratase activity; TAS:ProtInc.
 GO:0000062; F:fatty-acyl-CoA binding; IEA:Compara.
 GO:0016509; F:long-chain-3-hydroxyacyl-CoA dehydrogenase activity; IEA:EC.
 GO:0016508; F:long-chain-enoyl-CoA hydratase activity; IEA:Compara.
 GO:0051287; F:NAD binding; IEA:Compara.
 GO:0035965; P:cardiolipin acyl-chain remodeling; TAS:Reactome.
 GO:0006635; P:fatty acid beta-oxidation; TAS:Reactome.
 GO:0046474; P:glycerophospholipid biosynthetic process; TAS:Reactome.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0032868; P:response to insulin stimulus; IEA:Compara. 
Interpro
 IPR006180; 3-OHacyl-CoA_DH_CS.
 IPR006176; 3-OHacyl-CoA_DH_NAD-bd.
 IPR006108; 3HC_DH_C.
 IPR008927; 6-PGluconate_DH_C-like.
 IPR001753; Crotonase_core_superfam.
 IPR013328; DH_multihelical.
 IPR018376; Enoyl-CoA_hyd/isom_CS.
 IPR012803; Fa_ox_alpha_mit.
 IPR016040; NAD(P)-bd_dom. 
Pfam
 PF00725; 3HCDH
 PF02737; 3HCDH_N
 PF00378; ECH 
SMART
  
PROSITE
 PS00067; 3HCDH
 PS00166; ENOYL_COA_HYDRATASE 
PRINTS