HSD17B4

D-bifunctional protein (DBP), also known as peroxisomal multifunctional enzyme type 2 (MFP-2), as well as 17β-hydroxysteroid dehydrogenase type IV (17β-HSD type IV) is a protein that in humans is encoded by the HSD17B4 gene. It's an alcohol oxidoreductase, specifically 17β-Hydroxysteroid dehydrogenase. It is involved in fatty acid β-oxidation and steroid metabolism (cf. steroidogenesis).

HSD17B4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IKT, 1S9C, 1ZBQ
Identifiers
Aliases	HSD17B4, DBP, MFE-2, MPF-2, PRLTS1, SDR8C1, hydroxysteroid (17-beta) dehydrogenase 4, hydroxysteroid 17-beta dehydrogenase 4
External IDs	OMIM: 601860 MGI: 105089 HomoloGene: 358 GeneCards: HSD17B4
Gene location (Human) Chr. Chromosome 5 (human) Band 5q23.1 Start 119,452,473 bp End 119,637,199 bp
Gene location (Mouse) Chr. Chromosome 18 (mouse) Band 18|18 D1 Start 50,261,268 bp End 50,329,336 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of thyroid gland right lobe of liver left lobe of thyroid gland corpus callosum internal globus pallidus body of pancreas left adrenal gland seminal vesicula Achilles tendon jejunal mucosa Top expressed in saccule left lobe of liver ectoderm otic placode brown adipose tissue external carotid artery intercostal muscle lacrimal gland white adipose tissue internal carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity isomerase activity lyase activity 3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity oxidoreductase activity long-chain-enoyl-CoA hydratase activity signaling receptor binding 17-beta-hydroxysteroid dehydrogenase (NAD+) activity 3-hydroxyacyl-CoA dehydrogenase activity Cellular component membrane peroxisome peroxisomal membrane peroxisomal matrix mitochondrion cytosol Biological process estrogen metabolic process androgen metabolic process lipid metabolism alpha-linolenic acid metabolic process very long-chain fatty acid metabolic process Sertoli cell development fatty acid metabolic process very long-chain fatty-acyl-CoA metabolic process fatty acid beta-oxidation using acyl-CoA oxidase osteoblast differentiation medium-chain fatty-acyl-CoA metabolic process fatty acid beta-oxidation bile acid biosynthetic process protein targeting to peroxisome Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3295 15488 Ensembl ENSG00000133835 ENSMUSG00000024507 UniProt P51659 P51660 RefSeq (mRNA) NM_001292028 NM_000414 NM_001199291 NM_001199292 NM_001292027 NM_008292 RefSeq (protein) NP_000405 NP_001186220 NP_001186221 NP_001278956 NP_001278957 NP_001361426 NP_001361427 NP_001361428 NP_001361429 NP_001361430 NP_001361431 NP_001361432 NP_032318 Location (UCSC) Chr 5: 119.45 – 119.64 Mb Chr 18: 50.26 – 50.33 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

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]

See also

• D-bifunctional protein deficiency
• Perrault syndrome

Further reading

• de Launoit Y, Adamski J (June 1999). "Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome". Journal of Molecular Endocrinology. 22 (3): 227–40. doi:10.1677/jme.0.0220227. PMID 10343282.
• Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP (September 2006). "Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1761 (9): 973–94. doi:10.1016/j.bbalip.2006.04.006. PMID 16766224.
• Palosaari PM, Hiltunen JK (February 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". The Journal of Biological Chemistry. 265 (5): 2446–9. doi:10.1016/S0021-9258(19)39819-9. PMID 2303409.
• Adamski J, Normand T, Leenders F, Monté D, Begue A, Stéhelin D, Jungblut PW, de Launoit Y (October 1995). "Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV". The Biochemical Journal. 311 ( Pt 2) (2): 437–43. doi:10.1042/bj3110437. PMC 1136019. PMID 7487879.
• Markus M, Husen B, Adamski J (December 1995). "The subcellular localization of 17 beta-hydroxysteroid dehydrogenase type 4 and its interaction with actin". The Journal of Steroid Biochemistry and Molecular Biology. 55 (5–6): 617–21. doi:10.1016/0960-0760(95)00213-8. PMID 8547189. S2CID 36279864.
• Jiang LL, Kobayashi A, Matsuura H, Fukushima H, Hashimoto T (September 1996). "Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase". Journal of Biochemistry. 120 (3): 624–32. doi:10.1093/oxfordjournals.jbchem.a021458. PMID 8902629.
• Jiang LL, Miyazawa S, Souri M, Hashimoto T (February 1997). "Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein". Journal of Biochemistry. 121 (2): 364–9. doi:10.1093/oxfordjournals.jbchem.a021596. PMID 9089413.
• Jiang LL, Kurosawa T, Sato M, Suzuki Y, Hashimoto T (March 1997). "Physiological role of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein". Journal of Biochemistry. 121 (3): 506–13. doi:10.1093/oxfordjournals.jbchem.a021615. PMID 9133619.
• Novikov D, Dieuaide-Noubhani M, Vermeesch JR, Fournier B, Mannaerts GP, Van Veldhoven PP (May 1997). "The human peroxisomal multifunctional protein involved in bile acid synthesis: activity measurement, deficiency in Zellweger syndrome and chromosome mapping". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1360 (3): 229–40. doi:10.1016/s0925-4439(97)00003-3. PMID 9197465.
• Suzuki Y, Jiang LL, Souri M, Miyazawa S, Fukuda S, Zhang Z, Une M, Shimozawa N, Kondo N, Orii T, Hashimoto T (November 1997). "D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder". American Journal of Human Genetics. 61 (5): 1153–62. doi:10.1086/301599. PMC 1716023. PMID 9345094.
• van Grunsven EG, van Berkel E, Ijlst L, Vreken P, de Klerk JB, Adamski J, Lemonde H, Clayton PT, Cuebas DA, Wanders RJ (March 1998). "Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency". Proceedings of the National Academy of Sciences of the United States of America. 95 (5): 2128–33. Bibcode:1998PNAS...95.2128V. doi:10.1073/pnas.95.5.2128. PMC 19272. PMID 9482850.
• Dong Y, Qiu QQ, Debear J, Lathrop WF, Bertolini DR, Tamburini PP (October 1998). "17Beta-hydroxysteroid dehydrogenases in human bone cells". Journal of Bone and Mineral Research. 13 (10): 1539–46. doi:10.1359/jbmr.1998.13.10.1539. PMID 9783542. S2CID 85168465.
• Leenders F, Dolez V, Begue A, Möller G, Gloeckner JC, de Launoit Y, Adamski J (December 1998). "Structure of the gene for the human 17beta-hydroxysteroid dehydrogenase type IV". Mammalian Genome. 9 (12): 1036–41. doi:10.1007/s003359900921. PMID 9880674. S2CID 31749993.
• Green VL, Speirs V, Landolt AM, Foy PM, Atkin SL (April 1999). "17Beta-hydroxysteroid dehydrogenase type 1, 2, 3, and 4 expression and enzyme activity in human anterior pituitary adenomas". The Journal of Clinical Endocrinology and Metabolism. 84 (4): 1340–5. doi:10.1210/jcem.84.4.5619. PMID 10199776.
• van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ (August 1999). "Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency". Human Molecular Genetics. 8 (8): 1509–16. doi:10.1093/hmg/8.8.1509. PMID 10400999.
• Itoh M, Suzuki Y, Takashima S (June 1999). "A novel peroxisomal enzyme, D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein: its expression in the developing human brain". Microscopy Research and Technique. 45 (6): 383–8. doi:10.1002/(SICI)1097-0029(19990615)45:6<383::AID-JEMT5>3.0.CO;2-7. PMID 10402265. S2CID 26589734.
• Möller G, Leenders F, van Grunsven EG, Dolez V, Qualmann B, Kessels MM, Markus M, Krazeisen A, Husen B, Wanders RJ, de Launoit Y, Adamski J (1999). "Characterization of the HSD17B4 gene: D-specific multifunctional protein 2/17beta-hydroxysteroid dehydrogenase IV". The Journal of Steroid Biochemistry and Molecular Biology. 69 (1–6): 441–6. doi:10.1016/S0960-0760(99)00066-7. PMID 10419023. S2CID 33700582.
• Haapalainen AM, van Aalten DM, Meriläinen G, Jalonen JE, Pirilä P, Wierenga RK, Hiltunen JK, Glumoff T (November 2001). "Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution". Journal of Molecular Biology. 313 (5): 1127–38. CiteSeerX 10.1.1.417.9893. doi:10.1006/jmbi.2001.5084. PMID 11700068.