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Identification
HMDB Protein ID HMDBP00476
Secondary Accession Numbers
  • 5716
  • HMDBP04495
Name Peroxisomal multifunctional enzyme type 2
Synonyms
  1. 17-beta-HSD 4
  2. 17-beta-hydroxysteroid dehydrogenase 4
  3. 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase
  4. 3-hydroxyacyl-CoA dehydrogenase
  5. D-bifunctional protein
  6. DBP
  7. MFE-2
  8. Multifunctional protein 2
  9. MPF-2
Gene Name HSD17B4
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function 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.
Pathways
  • 27-Hydroxylase Deficiency
  • Bile Acid Biosynthesis
  • Cerebrotendinous Xanthomatosis (CTX)
  • Congenital Bile Acid Synthesis Defect Type II
  • Congenital Bile Acid Synthesis Defect Type III
  • Familial Hypercholanemia (FHCA)
  • fatty acid beta-oxidation
  • Peroxisome
  • Primary bile acid biosynthesis
  • Zellweger Syndrome
Reactions
(R)-3-hydroxyacyl-CoA + NAD → 3-oxoacyl-CoA + NADH details
(24R,25R)-3-alpha,7-alpha,12-alpha,24-tetrahydroxy-5-beta-cholestanoyl-CoA → (24E)-3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA + Water details
(3R)-3-hydroxyacyl-CoA → (2E)-2-enoyl-CoA + Water details
3a,7a-Dihydroxy-5b-cholest-24-enoyl-CoA + Water → 3 alpha,7 alpha,24-Trihydroxy-5beta-cholestanoyl-CoA details
3 alpha,7 alpha,24-Trihydroxy-5beta-cholestanoyl-CoA + NAD → 3a,7a-Dihydroxy-5b-24-oxocholestanoyl-CoA + NADH + Hydrogen Ion details
3a,7a,12a,24-Tetrahydroxy-5b-cholestanoyl-CoA + NAD → 3a,7a,12a-Trihydroxy-5b-24-oxocholestanoyl-CoA + NADH + Hydrogen Ion details
3a,7a,12a,24-Tetrahydroxy-5b-cholestanoyl-CoA → 3a,7a,12a-Trihydroxy-5b-cholest-24-enoyl-CoA + Water details
GO Classification
Biological Process
bile acid biosynthetic process
estrogen metabolic process
alpha-linolenic acid metabolic process
fatty acid beta-oxidation using acyl-CoA oxidase
medium-chain fatty-acyl-CoA metabolic process
androgen metabolic process
very long-chain fatty-acyl-CoA metabolic process
Cellular Component
peroxisomal matrix
peroxisomal membrane
Function
binding
catalytic activity
oxidoreductase activity
steroid binding
sterol binding
lipid binding
Molecular Function
protein homodimerization activity
17-beta-hydroxysteroid dehydrogenase (NAD+) activity
3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity
long-chain-enoyl-CoA hydratase activity
sterol binding
3-hydroxyacyl-CoA dehydrogenase activity
isomerase activity
nucleotide binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Peroxisome
Gene Properties
Chromosome Location 5
Locus 5q21
SNPs HSD17B4
Gene Sequence
>2211 bp
ATGGGCTCACCGCTGAGGTTCGACGGGCGGGTGGTACTGGTCACCGGCGCGGGGGCAGGA
TTGGGCCGAGCCTATGCCCTGGCTTTTGCAGAAAGAGGAGCGTTAGTTGTTGTGAATGAT
TTGGGAGGGGACTTCAAAGGAGTTGGTAAAGGCTCCTTAGCTGCTGATAAGGTTGTTGAA
GAAATAAGAAGGAGAGGTGGAAAAGCAGTGGCCAACTATGATTCAGTGGAAGAAGGAGAG
AAGGTTGTGAAGACAGCCCTGGATGCTTTTGGAAGAATAGATGTTGTGGTCAACAATGCT
GGAATTCTGAGGGATCGTTCCTTTGCTAGGATAAGTGATGAAGACTGGGATATAATCCAC
AGAGTTCATTTGCGGGGTTCATTCCAAGTGACACGGGCAGCATGGGAACACATGAAGAAA
CAGAAGTATGGAAGGATTATTATGACTTCATCAGCTTCAGGAATATATGGCAACTTTGGC
CAGGCCAATTATAGTGCTGCAAAGTTGGGTCTTCTGGGCCTTGCAAATTCTCTTGCAATT
GAAGGCAGGAAAAGCAACATTCATTGTAACACCATTGCTCCTAATGCGGGATCACGGATG
ACTCAGACAGTTATGCCTGAAGATCTTGTGGAAGCCCTGAAGCCAGAGTATGTGGCACCT
CTTGTCCTTTGGCTTTGTCACGAGAGTTGTGAGGAGAATGGTGGCTTGTTTGAGGTTGGA
GCAGGATGGATTGGAAAATTACGCTGGGAGCGGACTCTTGGAGCTATTGTAAGACAAAAG
AATCACCCAATGACTCCTGAGGCAGTCAAGGCTAACTGGAAGAAGATCTGTGACTTTGAG
AATGCCAGCAAGCCTCAGAGTATCCAAGAATCAACTGGCAGTATAATTGAAGTTCTGAGT
AAAATAGATTCAGAAGGAGGAGTTTCAGCAAATCATACTAGTCGTGCAACGTCTACAGCA
ACATCAGGATTTGCTGGAGCTATTGGCCAGAAACTCCCTCCATTTTCTTATGCTTATACG
GAACTGGAAGCTATTATGTATGCCCTTGGAGTGGGAGCGTCAATCAAGGATCCAAAAGAT
TTGAAATTTATTTATGAAGGAAGTTCTGATTTCTCCTGTTTGCCCACCTTCGGAGTTATC
ATAGGTCAGAAATCTATGATGGGTGGAGGATTAGCAGAAATTCCTGGACTTTCAATCAAC
TTTGCAAAGGTTCTTCATGGAGAGCAGTACTTAGAGTTATATAAACCACTTCCCAGAGCA
GGAAAATTAAAATGTGAAGCAGTTGTTGCTGATGTCCTAGATAAAGGATCCGGTGTAGTG
ATTATTATGGATGTCTATTCTTATTCTGAGAAGGAACTTATATGCCACAATCAGTTCTCT
CTCTTTCTTGTTGGCTCTGGAGGCTTTGGTGGAAAACGGACATCAGACAAAGTCAAGGTA
GCTGTAGCCATACCTAATAGACCTCCTGATGCTGTACTTACAGATACCACCTCTCTTAAT
CAGGCTGCTTTGTACCGCCTCAGTGGAGACTGGAATCCCTTACACATTGATCCTAACTTT
GCTAGTCTAGCAGGTTTTGACAAGCCCATATTACATGGATTATGTACATTTGGATTTTCT
GCCAGGCGTGTGTTACAGCAGTTTGCAGATAATGATGTGTCAAGATTCAAGGCAATTAAG
GCTCGTTTTGCAAAACCAGTATATCCAGGACAAACTCTACAAACTGAGATGTGGAAGGAA
GGAAACAGAATTCATTTTCAAACCAAGGTCCAAGAAACTGGAGACATTGTCATTTCAAAT
GCATATGTGGATCTTGCACCAACATCTGGTACTTCAGCTAAGACACCCTCTGAGGGCGGG
AAGCTTCAGAGTACCTTTGTATTTGAGGAAATAGGACGCCGCCTAAAGGATATTGGGCCT
GAGGTGGTGAAGAAAGTAAATGCTGTATTTGAGTGGCATATAACCAAAGGCGGAAATATT
GGGGCTAAGTGGACTATTGACCTGAAAAGTGGTTCTGGAAAAGTGTACCAAGGCCCTGCA
AAAGGTGCTGCTGATACAACAATCATACTTTCAGATGAAGATTTCATGGAGGTGGTCCTG
GGCAAGCTTGACCCTCAGAAGGCATTCTTTAGTGGCAGGCTGAAGGCCAGAGGGAACATC
ATGCTGAGCCAGAAACTTCAGATGATTCTTAAAGACTACGCCAAGCTCTGA
Protein Properties
Number of Residues 736
Molecular Weight 79685.715
Theoretical pI 8.832
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Peroxisomal multifunctional enzyme type 2
MGSPLRFDGRVVLVTGAGAGLGRAYALAFAERGALVVVNDLGGDFKGVGKGSLAADKVVE
EIRRRGGKAVANYDSVEEGEKVVKTALDAFGRIDVVVNNAGILRDRSFARISDEDWDIIH
RVHLRGSFQVTRAAWEHMKKQKYGRIIMTSSASGIYGNFGQANYSAAKLGLLGLANSLAI
EGRKSNIHCNTIAPNAGSRMTQTVMPEDLVEALKPEYVAPLVLWLCHESCEENGGLFEVG
AGWIGKLRWERTLGAIVRQKNHPMTPEAVKANWKKICDFENASKPQSIQESTGSIIEVLS
KIDSEGGVSANHTSRATSTATSGFAGAIGQKLPPFSYAYTELEAIMYALGVGASIKDPKD
LKFIYEGSSDFSCLPTFGVIIGQKSMMGGGLAEIPGLSINFAKVLHGEQYLELYKPLPRA
GKLKCEAVVADVLDKGSGVVIIMDVYSYSEKELICHNQFSLFLVGSGGFGGKRTSDKVKV
AVAIPNRPPDAVLTDTTSLNQAALYRLSGDWNPLHIDPNFASLAGFDKPILHGLCTFGFS
ARRVLQQFADNDVSRFKAIKARFAKPVYPGQTLQTEMWKEGNRIHFQTKVQETGDIVISN
AYVDLAPTSGTSAKTPSEGGKLQSTFVFEEIGRRLKDIGPEVVKKVNAVFEWHITKGGNI
GAKWTIDLKSGSGKVYQGPAKGAADTTIILSDEDFMEVVLGKLDPQKAFFSGRLKARGNI
MLSQKLQMILKDYAKL
GenBank ID Protein 1050517
UniProtKB/Swiss-Prot ID P51659
UniProtKB/Swiss-Prot Entry Name DHB4_HUMAN
PDB IDs
GenBank Gene ID X87176
GeneCard ID HSD17B4
GenAtlas ID HSD17B4
HGNC ID HGNC:5213
References
General References
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  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  4. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  5. Adamski J, Normand T, Leenders F, Monte D, Begue A, Stehelin D, Jungblut PW, de Launoit Y: Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV. Biochem J. 1995 Oct 15;311 ( Pt 2):437-43. [PubMed:7487879 ]
  6. Jiang LL, Miyazawa S, Souri M, Hashimoto T: Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein. J Biochem. 1997 Feb;121(2):364-9. [PubMed:9089413 ]
  7. Leenders F, Dolez V, Begue A, Moller G, Gloeckner JC, de Launoit Y, Adamski J: Structure of the gene for the human 17beta-hydroxysteroid dehydrogenase type IV. Mamm Genome. 1998 Dec;9(12):1036-41. [PubMed:9880674 ]
  8. Jiang LL, Kobayashi A, Matsuura H, Fukushima H, Hashimoto T: Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase. J Biochem. 1996 Sep;120(3):624-32. [PubMed:8902629 ]
  9. Haapalainen AM, van Aalten DM, Merilainen G, Jalonen JE, Pirila P, Wierenga RK, Hiltunen JK, Glumoff T: Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution. J Mol Biol. 2001 Nov 9;313(5):1127-38. [PubMed:11700068 ]
  10. Koski KM, Haapalainen AM, Hiltunen JK, Glumoff T: Crystal structure of 2-enoyl-CoA hydratase 2 from human peroxisomal multifunctional enzyme type 2. J Mol Biol. 2005 Feb 4;345(5):1157-69. Epub 2004 Dec 10. [PubMed:15644212 ]
  11. van Grunsven EG, van Berkel E, Ijlst L, Vreken P, de Klerk JB, Adamski J, Lemonde H, Clayton PT, Cuebas DA, Wanders RJ: Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2128-33. [PubMed:9482850 ]