HSD17B4

Hydroxysteroid (17-beta) dehydrogenase 4
PDB rendering based on 1ikt.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1IKT​, 1S9C​, 1ZBQ​
Identifiers
Symbols	HSD17B4 ; DBP; MFE-2; MPF-2; PRLTS1; SDR8C1
External IDs	OMIM: 601860 MGI: 105089 HomoloGene: 358 ChEMBL: 5814 GeneCards: HSD17B4 Gene
EC number	1.1.1.n12, 4.2.1.107, 4.2.1.119
Gene ontology Molecular function • 3-hydroxyacyl-CoA dehydrogenase activity • receptor binding • long-chain-enoyl-CoA hydratase activity • isomerase activity • 3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity • protein homodimerization activity • 17-beta-hydroxysteroid dehydrogenase (NAD+) activity Cellular component • mitochondrion • peroxisome • peroxisomal membrane • peroxisomal matrix • membrane • intracellular membrane-bounded organelle Biological process • very long-chain fatty acid metabolic process • osteoblast differentiation • fatty acid beta-oxidation • bile acid biosynthetic process • bile acid metabolic process • androgen metabolic process • estrogen metabolic process • fatty acid beta-oxidation using acyl-CoA oxidase • unsaturated fatty acid metabolic process • alpha-linolenic acid metabolic process • very long-chain fatty-acyl-CoA metabolic process • medium-chain fatty-acyl-CoA metabolic process • cellular lipid metabolic process • small molecule metabolic process • oxidation-reduction process • Sertoli cell development Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3295	15488
Ensembl	ENSG00000133835	ENSMUSG00000024507
UniProt	P51659	P51660
RefSeq (mRNA)	NM_000414	NM_008292
RefSeq (protein)	NP_000405	NP_032318
Location (UCSC)	Chr 5: 119.45 – 119.64 Mb	Chr 18: 50.13 – 50.2 Mb
PubMed search

Peroxisomal multifunctional enzyme type 2 is a protein that in humans is encoded by the HSD17B4 gene.^[1][2][3]

The HSD17B4 gene encodes an enzyme involved in peroxisomal fatty acid beta-oxidation. It was first identified as a 17-beta-estradiol dehydrogenase (Leenders et al., 1996; van Grunsven et al., 1998). Peroxisomal beta-oxidation of fatty acids, originally described by Lazarow and de Duve (1976), is catalyzed by 3 enzymes: acyl-CoA oxidase (see, e.g., ACOX1, MIM 609751); the 'D-bifunctional enzyme,' with enoyl-CoA-hydratase and D-3-hydroxyacyl-CoA dehydrogenase activity, and 3-ketoacyl-CoA thiolase (MIM 604054).

See also the L-bifunctional peroxisomal protein (EHHADH; MIM 607037). The D- and L-bifunctional proteins have different substrate specificities. The D-bifunctional protein catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids and also acts in shortening cholesterol for bile acid formation. In contrast, the L-specific bifunctional protein does not have the latter 2 activities (Jiang et al., 1997).[supplied by OMIM]^[3]

See also

• D-bifunctional protein deficiency

References

1. Leenders F, Prescher G, Dolez V, Begue A, de Launoit Y, Adamski J (Mar 1997). "Assignment of human 17 beta-hydroxysteroid dehydrogenase IV to chromosome 5q2 by fluorescence in situ hybridization". Genomics 37 (3): 403–4. doi:10.1006/geno.1996.0578. PMID 8938456.
2. Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jornvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Feb 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chem Biol Interact 178 (1-3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
3. "Entrez Gene: HSD17B4 hydroxysteroid (17-beta) dehydrogenase 4".

Further reading

• de Launoit Y, Adamski J (1999). "Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome.". J. Mol. Endocrinol. 22 (3): 227–40. doi:10.1677/jme.0.0220227. PMID 10343282.
• Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP (2006). "Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model.". Biochim. Biophys. Acta 1761 (9): 973–94. doi:10.1016/j.bbalip.2006.04.006. PMID 16766224.
• Palosaari PM, Hiltunen JK (1990). "Peroxisomal bifunctional protein from rat liver is a trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities.". J. Biol. Chem. 265 (5): 2446–9. PMID 2303409.
• Adamski J, Normand T, Leenders F, et al. (1995). "Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV.". Biochem. J. 311 (2): 437–43. PMC 1136019. PMID 7487879.
• Markus M, Husen B, Adamski J (1996). "The subcellular localization of 17 beta-hydroxysteroid dehydrogenase type 4 and its interaction with actin.". J. Steroid Biochem. Mol. Biol. 55 (5-6): 617–21. doi:10.1016/0960-0760(95)00213-8. PMID 8547189.
• Jiang LL, Kobayashi A, Matsuura H, et al. (1997). "Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase.". J. Biochem. 120 (3): 624–32. doi:10.1093/oxfordjournals.jbchem.a021458. PMID 8902629.
• Jiang LL, Miyazawa S, Souri M, Hashimoto T (1997). "Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein.". J. Biochem. 121 (2): 364–9. doi:10.1093/oxfordjournals.jbchem.a021596. PMID 9089413.
• Jiang LL, Kurosawa T, Sato M, et al. (1997). "Physiological role of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein.". J. Biochem. 121 (3): 506–13. doi:10.1093/oxfordjournals.jbchem.a021615. PMID 9133619.
• Novikov D, Dieuaide-Noubhani M, Vermeesch JR, et al. (1997). "The human peroxisomal multifunctional protein involved in bile acid synthesis: activity measurement, deficiency in Zellweger syndrome and chromosome mapping.". Biochim. Biophys. Acta 1360 (3): 229–40. doi:10.1016/s0925-4439(97)00003-3. PMID 9197465.
• Suzuki Y, Jiang LL, Souri M, et al. (1997). "D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder.". Am. J. Hum. Genet. 61 (5): 1153–62. doi:10.1086/301599. PMC 1716023. PMID 9345094.
• van Grunsven EG, van Berkel E, IJlst L, et al. (1998). "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. 95 (5): 2128–33. doi:10.1073/pnas.95.5.2128. PMC 19272. PMID 9482850.
• Dong Y, Qiu QQ, Debear J, et al. (1999). "17Beta-hydroxysteroid dehydrogenases in human bone cells.". J. Bone Miner. Res. 13 (10): 1539–46. doi:10.1359/jbmr.1998.13.10.1539. PMID 9783542.
• Leenders F, Dolez V, Begue A, et al. (1999). "Structure of the gene for the human 17beta-hydroxysteroid dehydrogenase type IV.". Mamm. Genome 9 (12): 1036–41. doi:10.1007/s003359900921. PMID 9880674.
• Green VL, Speirs V, Landolt AM, et al. (1999). "17Beta-hydroxysteroid dehydrogenase type 1, 2, 3, and 4 expression and enzyme activity in human anterior pituitary adenomas.". J. Clin. Endocrinol. Metab. 84 (4): 1340–5. doi:10.1210/jc.84.4.1340. PMID 10199776.
• van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ (1999). "Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency.". Hum. Mol. Genet. 8 (8): 1509–16. doi:10.1093/hmg/8.8.1509. PMID 10400999.
• Itoh M, Suzuki Y, Takashima S (1999). "A novel peroxisomal enzyme, D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein: its expression in the developing human brain.". Microsc. Res. Tech. 45 (6): 383–8. doi:10.1002/(SICI)1097-0029(19990615)45:6<383::AID-JEMT5>3.0.CO;2-7. PMID 10402265.
• Möller G, Leenders F, van Grunsven EG, et al. (1999). "Characterization of the HSD17B4 gene: D-specific multifunctional protein 2/17beta-hydroxysteroid dehydrogenase IV.". J. Steroid Biochem. Mol. Biol. 69 (1-6): 441–6. doi:10.1016/S0960-0760(99)00066-7. PMID 10419023.
• Haapalainen AM, van Aalten DM, Meriläinen G, et al. (2001). "Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution.". J. Mol. Biol. 313 (5): 1127–38. doi:10.1006/jmbi.2001.5084. PMID 11700068.