UniProt Accession

 DHB4_MOUSE; P51660; Q9DBM3 

Genbank Protein ID

 X89998; AK004866; AK088381; AK166801; AK167060; AK169077; BC022175 

Genbank Nucleotide ID

 CAA62015.1; BAB23627.1; BAC40317.1; BAE39029.1; BAE39222.1; BAE40862.1; AAH22175.1 

Protein Name

 Peroxisomal multifunctional enzyme type 2 

Protein Synonyms/Alias

 MFE-2; 17-beta-hydroxysteroid dehydrogenase 4; 17-beta-HSD 4; D-bifunctional protein; DBP; Multifunctional protein 2; MPF-2; (3R)-hydroxyacyl-CoA dehydrogenase; Enoyl-CoA hydratase 2; 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase 

Gene Name

 Hsd17b4 

Gene Synonyms/Alias

 Edh17b4 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
46	NDLGGDFKGIGKGSS	acetylation	[1, 2, 3, 4, 5, 6, 7]
46	NDLGGDFKGIGKGSS	succinylation	[6]
46	NDLGGDFKGIGKGSS	ubiquitination	[8]
57	KGSSAADKVVAEIRR	acetylation	[1, 2, 3, 4, 5, 6, 7]
57	KGSSAADKVVAEIRR	succinylation	[6]
57	KGSSAADKVVAEIRR	ubiquitination	[8]
68	EIRRKGGKAVANYDS	acetylation	[6]
68	EIRRKGGKAVANYDS	succinylation	[6]
68	EIRRKGGKAVANYDS	ubiquitination	[8]
81	DSVEAGEKLVKTALD	acetylation	[1, 2, 3, 6, 7]
81	DSVEAGEKLVKTALD	ubiquitination	[8]
84	EAGEKLVKTALDTFG	acetylation	[3, 6]
84	EAGEKLVKTALDTFG	succinylation	[6]
84	EAGEKLVKTALDTFG	ubiquitination	[8]
139	RAAWDHMKKQNYGRI	acetylation	[3, 6, 7]
139	RAAWDHMKKQNYGRI	succinylation	[6]
184	TLAIEGRKNNIHCNT	ubiquitination	[8]
275	AVRDNWEKICDFSNA	acetylation	[5, 6]
275	AVRDNWEKICDFSNA	succinylation	[6]
284	CDFSNASKPQTIQES	acetylation	[3]
284	CDFSNASKPQTIQES	ubiquitination	[8]
355	LGVGASVKNPKDLKF	acetylation	[6]
355	LGVGASVKNPKDLKF	succinylation	[6]
402	GLSFNFAKALHGEQY	ubiquitination	[8]
414	EQYLELYKPLPRSGE	acetylation	[3, 7]
414	EQYLELYKPLPRSGE	ubiquitination	[8]
423	LPRSGELKCEAVIAD	acetylation	[2, 3, 5, 6, 7]
423	LPRSGELKCEAVIAD	succinylation	[6]
423	LPRSGELKCEAVIAD	ubiquitination	[8]
476	GGKRTSEKLKAAVAV	acetylation	[7]
478	KRTSEKLKAAVAVPN	ubiquitination	[8]
564	AIKVRFAKPVYPGQT	acetylation	[3, 4, 5, 7, 9]
564	AIKVRFAKPVYPGQT	ubiquitination	[8]
578	TLQTEMWKEGNRIHF	acetylation	[3, 5, 6, 7]
578	TLQTEMWKEGNRIHF	succinylation	[6]
662	KGGTVAAKWTIDLKS	acetylation	[6, 10]
662	KGGTVAAKWTIDLKS	succinylation	[6]
668	AKWTIDLKSGSGEVY	acetylation	[7]
706	FGKLDPQKAFFSGRL	acetylation	[1, 3, 5, 7]
724	GNIMLSQKLQMILKD	acetylation	[6]
724	GNIMLSQKLQMILKD	succinylation	[6]
730	QKLQMILKDYAKL**	acetylation	[6]
730	QKLQMILKDYAKL**	succinylation	[6]

Reference

 [1] Mitochondrial acetylome analysis in a mouse model of alcohol-induced liver injury utilizing SIRT3 knockout mice.
 Fritz KS, Galligan JJ, Hirschey MD, Verdin E, Petersen DR.
 J Proteome Res. 2012 Mar 2;11(3):1633-43. [PMID: 22309199]
 [2] 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]
 [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] 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]
 [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] 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]
 [7] 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]
 [8] 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]
 [9] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [10] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647] 

Functional Description

 Bifunctional enzyme acting on the peroxisomal beta- oxidation pathway for fatty acids. Catalyzes the formation of 3- ketoacyl-CoA intermediates from both straight-chain and 2-methyl- branched-chain fatty acids (By similarity). 

Sequence Annotation

 DOMAIN 483 599 MaoC-like.
 DOMAIN 623 735 SCP2.
 NP_BIND 13 37 NAD (By similarity).
 NP_BIND 75 76 NAD (By similarity).
 NP_BIND 164 168 NAD (By similarity).
 NP_BIND 196 199 NAD (By similarity).
 REGION 2 305 (3R)-hydroxyacyl-CoA dehydrogenase.
 REGION 321 621 Enoyl-CoA hydratase 2.
 REGION 405 406 (3R)-3-hydroxydecanoyl-CoA binding (By
 REGION 509 514 (3R)-3-hydroxydecanoyl-CoA binding (By
 MOTIF 733 735 Microbody targeting signal (Potential).
 ACT_SITE 164 164 Proton acceptor (By similarity).
 BINDING 21 21 NAD; via amide nitrogen (By similarity).
 BINDING 40 40 NAD (By similarity).
 BINDING 99 99 NAD; via carbonyl oxygen (By similarity).
 BINDING 151 151 Substrate (By similarity).
 BINDING 434 434 (3R)-3-hydroxydecanoyl-CoA (By
 BINDING 532 532 (3R)-3-hydroxydecanoyl-CoA; via amide
 BINDING 562 562 (3R)-3-hydroxydecanoyl-CoA; via carbonyl
 BINDING 705 705 Substrate (By similarity).
 BINDING 723 723 Substrate (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 3 3 Phosphoserine.
 MOD_RES 304 304 Phosphoserine (By similarity).
 MOD_RES 308 308 Phosphoserine.
 MOD_RES 564 564 N6-acetyllysine (By similarity).
 MOD_RES 662 662 N6-acetyllysine.
 MOD_RES 668 668 N6-acetyllysine (By similarity).
 MOD_RES 706 706 N6-acetyllysine (By similarity).  

Keyword

 Acetylation; Complete proteome; Fatty acid metabolism; Isomerase; Lipid metabolism; Lyase; NAD; Oxidoreductase; Peroxisome; Phosphoprotein; Reference proteome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 735 AA 

Protein Sequence

Gene Ontology

 GO:0005739; C:mitochondrion; IDA:MGI.
 GO:0005777; C:peroxisome; IDA:MGI.
 GO:0033989; F:3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity; IEA:EC.
 GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
 GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:EC.
 GO:0032934; F:sterol binding; IEA:InterPro.
 GO:0006635; P:fatty acid beta-oxidation; IMP:MGI.
 GO:0060009; P:Sertoli cell development; IMP:MGI.
 GO:0000038; P:very long-chain fatty acid metabolic process; IMP:MGI. 

Interpro

 IPR002198; DH_sc/Rdtase_SDR.
 IPR002347; Glc/ribitol_DH.
 IPR002539; MaoC_dom.
 IPR016040; NAD(P)-bd_dom.
 IPR020904; Sc_DH/Rdtase_CS.
 IPR003033; SCP2_sterol-bd_dom. 

Pfam

 PF00106; adh_short
 PF01575; MaoC_dehydratas
 PF02036; SCP2 

SMART

  

PROSITE

 PS00061; ADH_SHORT 

PRINTS

 PR00081; GDHRDH.
 PR00080; SDRFAMILY.