Protein-coding gene in the species Homo sapiens
HSD17B4 |
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![](//upload.wikimedia.org/wikipedia/commons/thumb/4/4a/Protein_HSD17B4_PDB_1ikt.png/250px-Protein_HSD17B4_PDB_1ikt.png) |
Available structures |
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PDB | Ortholog search: PDBe RCSB |
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List of PDB id codes |
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1IKT, 1S9C, 1ZBQ |
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Identifiers |
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Aliases | HSD17B4, DBP, MFE-2, MPF-2, PRLTS1, SDR8C1, hydroxysteroid (17-beta) dehydrogenase 4, hydroxysteroid 17-beta dehydrogenase 4 |
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External IDs | OMIM: 601860; MGI: 105089; HomoloGene: 358; GeneCards: HSD17B4; OMA:HSD17B4 - orthologs |
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Gene location (Human) |
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![Chromosome 5 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/6/61/Ideogram_human_chromosome_5.svg/300px-Ideogram_human_chromosome_5.svg.png) | Chr. | Chromosome 5 (human)[1] |
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| Band | 5q23.1 | Start | 119,452,473 bp[1] |
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End | 119,637,199 bp[1] |
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Gene location (Mouse) |
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![Chromosome 18 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/5/5c/Ideogram_house_mouse_chromosome_18.svg/260px-Ideogram_house_mouse_chromosome_18.svg.png) | Chr. | Chromosome 18 (mouse)[2] |
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| Band | 18|18 D1 | Start | 50,261,268 bp[2] |
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End | 50,329,336 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - right lobe of thyroid gland
- right lobe of liver
- left lobe of thyroid gland
- corpus callosum
- internal globus pallidus
- right adrenal cortex
- C1 segment
- body of pancreas
- left adrenal gland
- left adrenal cortex
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| Top expressed in | - saccule
- left lobe of liver
- ectoderm
- otic vesicle
- otic placode
- brown adipose tissue
- external carotid artery
- intercostal muscle
- lacrimal gland
- white adipose tissue
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| More reference expression data |
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BioGPS | ![](//upload.wikimedia.org/wikipedia/commons/thumb/c/c2/PBB_GE_HSD17B4_201413_at_fs.png/250px-PBB_GE_HSD17B4_201413_at_fs.png) | More reference expression data |
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Gene ontology |
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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 |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | |
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NM_001292028 NM_000414 NM_001199291 NM_001199292 NM_001292027 |
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RefSeq (protein) | NP_000405 NP_001186220 NP_001186221 NP_001278956 NP_001278957
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NP_001361426 NP_001361427 NP_001361428 NP_001361429 NP_001361430 NP_001361431 NP_001361432 |
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Location (UCSC) | Chr 5: 119.45 – 119.64 Mb | Chr 18: 50.26 – 50.33 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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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.[5][6][7][8] It's an alcohol oxidoreductase, specifically 17β-Hydroxysteroid dehydrogenase. It is involved in fatty acid β-oxidation and steroid metabolism (cf. steroidogenesis).[8]
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][7]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000133835 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024507 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Leenders F, Prescher G, Dolez V, Begue A, de Launoit Y, Adamski J (November 1996). "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.
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- ^ a b "Entrez Gene: HSD17B4 hydroxysteroid (17-beta) dehydrogenase 4".
- ^ a b 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.
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.
PDB gallery
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1ikt: LIGANDED STEROL CARRIER PROTEIN TYPE 2 (SCP-2) LIKE DOMAIN OF HUMAN MULTIFUNCTIONAL ENZYME TYPE 2 (MFE-2) -
1s9c: Crystal structure analysis of the 2-enoyl-CoA hydratase 2 domain of human peroxisomal multifunctional enzyme type 2 -
1zbq: Crystal Structure Of Human 17-Beta-Hydroxysteroid Dehydrogenase Type 4 In Complex With NAD |
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Transporters | |
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Structure/Peroxin | |
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LAMP | |
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see also intermediates, disorders |
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