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    HSD17B4 hydroxysteroid (17-beta) dehydrogenase 4 [ Homo sapiens ]

    Gene ID: 3295, updated on 12-May-2012
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    Summary

    Official Symbol
    HSD17B4provided by HGNC
    Official Full Name
    hydroxysteroid (17-beta) dehydrogenase 4provided by HGNC
    Primary source
    HGNC:5213
    See related
    Ensembl:ENSG00000133835; HPRD:03514; MIM:601860; Vega:OTTHUMG00000128899
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    DBP; MFE-2; MPF-2; SDR8C1
    Summary
    The protein encoded by this gene is a bifunctional enzyme that is involved in the peroxisomal beta-oxidation pathway for fatty acids. It also acts as a catalyst for the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids. Defects in this gene that affect the peroxisomal fatty acid beta-oxidation activity are a cause of D-bifunctional protein deficiency (DBPD). An apparent pseudogene of this gene is present on chromosome 8. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    5q21
    Sequence :
    Chromosome: 5; NC_000005.9 (118788138..118878030)
    See HSD17B4 in Epigenomics, MapViewer

    Chromosome 5 - NC_000005.9Genomic Context describing neighboring genes Neighboring gene Dmx-like 1 Neighboring gene septin 7 pseudogene Neighboring gene tumor necrosis factor, alpha-induced protein 8 Neighboring gene ribosomal protein L21 pseudogene 58 Neighboring gene fatty acid binding protein 5 pseudogene 6

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. Danielsen JM, et al. Mol Cell Proteomics, 2011 Mar. PMID 21139048.
    2. Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma. Grønborg S, et al. Am J Med Genet A, 2010 Nov. PMID 20949532.
    3. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. Hendrickson SL, et al. PLoS One, 2010 Sep 21. PMID 20877624.
    4. A large-scale candidate gene association study of age at menarche and age at natural menopause. He C, et al. Hum Genet, 2010 Nov. PMID 20734064.
    5. Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. Pierce SB, et al. Am J Hum Genet, 2010 Aug 13. PMID 20673864.

    See all (64) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. The diagnosis of a type III DBPD with a missense mutation (T15A) in the HSD17B4 gene, coding for D-bifunctional protein (DBP), could be established.
      Title: Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma.
    2. MFE2 anchors its substrate around the region from Trp(249) to Arg(251) and positions the substrate along the hydrophobic cavity in the proper direction toward the catalytic center
      Title: Identification of a substrate-binding site in a peroxisomal beta-oxidation enzyme by photoaffinity labeling with a novel palmitoyl derivative.
    3. Meta-analysis of gene-disease association. (HuGE Navigator)
      Title: Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium.
    4. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    5. Perrault syndrome and DBP deficiency overlap clinically and Perrault syndrome is genetically heterogeneous.
      Title: Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome.
    6. rs11205 in HSD17B4 was associated with testicular germ cell tumor. Risk doubled per copy of the minor A allele. Homozygosity of this allele quadrupled the risk vs. homozygous major G allele. The risk was increased both for seminoma & nonseminoma.
      Title: Association of testicular germ cell tumor with polymorphisms in estrogen receptor and steroid metabolism genes.
    7. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes.
    8. HSD17B4 is not only associated with the presence of prostate cancer, but is also a significant independent predictor of poor patient outcome.
      Title: HSD17B4 overexpression, an independent biomarker of poor patient outcome in prostate cancer.
    9. HSD17B4 mRNA is expressed in human skin, at similar levels in men and women. HSD17B4 levels are not altered by topical 17-beta-estradiol treatment.
      Title: Induction of collagen by estradiol: difference between sun-protected and photodamaged human skin in vivo.
    10. Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Inherited variation in the androgen pathway is associated with the efficacy of androgen-deprivation therapy in men with prostate cancer.
    Submit: New GeneRIF Correction See all (13)
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    Phenotypes

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    D-bifunctional protein deficiency

    Perrault syndrome

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P51659 P60709 ACTB    HPRD  PubMed  
    P51659 Q92597 NDRG1    HPRD  PubMed  
    BioGRID:109528 BioGRID:115669 NDRG1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109528 BioGRID:122964 UBA5    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109528 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    • Homologs of the HSD17B4 gene: The HSD17B4 gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, , , N.crassa, A.thaliana, and rice.
    • Map Viewer (Mouse, Rat)

    Pathways from BioSystems

    • Beta-oxidation of pristanoyl-CoA, organism-specific biosystem (from REACTOME)
      Beta-oxidation of pristanoyl-CoA, organism-specific biosystemPristanoyl-CoA, generated in the peroxisome by alpha-oxidation of dietary phytanic acid, is further catabolized by three cycles of peroxisomal beta-oxidation to yield 4,8-dimethylnonanoyl-CoA, acetyl...
    • Beta-oxidation of very long chain fatty acids, organism-specific biosystem (from REACTOME)
      Beta-oxidation of very long chain fatty acids, organism-specific biosystemLinear fatty acids containing more than 18 carbons are broken down by beta-oxidation in peroxisomes to yield acetyl-CoA and medium chain-length fatty acyl CoA's such as octanoyl-CoA (Wanders and Wate...
    • Bile acid and bile salt metabolism, organism-specific biosystem (from REACTOME)
      Bile acid and bile salt metabolism, organism-specific biosystemIn a healthy adult human, about 500 mg of cholesterol is converted to bile salts daily. Newly synthesized bile salts are secreted into the bile and released into the small intestine where they emulsi...
    • Bile acid biosynthesis, cholesterol => cholate, organism-specific biosystem (from KEGG)
      Bile acid biosynthesis, cholesterol => cholate, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Sterol biosynthesis
    • Bile acid biosynthesis, cholesterol => cholate, conserved biosystem (from KEGG)
      Bile acid biosynthesis, cholesterol => cholate, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Sterol biosynthesis
    • Metabolic pathways, organism-specific biosystem (from KEGG)
      Metabolic pathways, organism-specific biosystem
      Metabolic pathways
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
      Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
    • Peroxisomal lipid metabolism, organism-specific biosystem (from REACTOME)
      Peroxisomal lipid metabolism, organism-specific biosystemIn humans, the catabolism of phytanate, pristanate, and very long chain fatty acids as well as the first four steps of the biosynthesis of plasmalogens are catalyzed by peroxisomal enzymes. Defects i...
    • Peroxisome, organism-specific biosystem (from KEGG)
      Peroxisome, organism-specific biosystemPeroxisomes are essential organelles that play a key role in redox signalling and lipid homeostasis. They contribute to many crucial metabolic processes such as fatty acid oxidation, biosynthesis of ...
    • Peroxisome, conserved biosystem (from KEGG)
      Peroxisome, conserved biosystemPeroxisomes are essential organelles that play a key role in redox signalling and lipid homeostasis. They contribute to many crucial metabolic processes such as fatty acid oxidation, biosynthesis of ...
    • Primary bile acid biosynthesis, organism-specific biosystem (from KEGG)
      Primary bile acid biosynthesis, organism-specific biosystemBile acids are steroid carboxylic acids derived from cholesterol in vertebrates. The primary bile acids, cholic acid and chenodeoxycholic acid, are synthesized in the liver and conjugated with taurin...
    • Primary bile acid biosynthesis, conserved biosystem (from KEGG)
      Primary bile acid biosynthesis, conserved biosystemBile acids are steroid carboxylic acids derived from cholesterol in vertebrates. The primary bile acids, cholic acid and chenodeoxycholic acid, are synthesized in the liver and conjugated with taurin...
    • Steroid Biosynthesis, organism-specific biosystem (from WikiPathways)
      Steroid Biosynthesis, organism-specific biosystem
      Steroid Biosynthesis
    • Synthesis of bile acids and bile salts, organism-specific biosystem (from REACTOME)
      Synthesis of bile acids and bile salts, organism-specific biosystemIn a healthy adult human, about 500 mg of cholesterol is converted to bile salts daily (Russell 2003). The major pathway for bile salt synthesis in the liver begins with the conversion of cholesterol...
    • Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol, organism-specific biosystem (from REACTOME)
      Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol, organism-specific biosystemIn the liver, synthesis of bile acids and bile salts is initiated with the conversion of cholesterol to 7alpha-hydroxycholesterol and of 7alpha-hydroxycholesterol to 4-cholesten-7alpha-ol-3-one. The ...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    3-hydroxyacyl-CoA dehydrogenase activity TAS
    Traceable Author Statement
    more info
    		  
    3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity TAS
    Traceable Author Statement
    more info
    		  
    estradiol 17-beta-dehydrogenase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    isomerase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    long-chain-enoyl-CoA hydratase activity TAS
    Traceable Author Statement
    more info
    		  
    lyase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    oxidoreductase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    sterol binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    sterol transporter activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    bile acid biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    bile acid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    cellular lipid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    fatty acid beta-oxidation using acyl-CoA oxidase TAS
    Traceable Author Statement
    more info
    		  
    fatty acid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    small molecule metabolic process TAS
    Traceable Author Statement
    more info
    		  
    sterol transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    peroxisomal matrix TAS
    Traceable Author Statement
    more info
    		  
    peroxisome IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    peroxisomal multifunctional enzyme type 2
    Names
    peroxisomal multifunctional enzyme type 2
    17-beta-HSD 4
    17-beta-HSD IV
    beta-keto-reductase
    multifunctional protein 2
    beta-hydroxyacyl dehydrogenase
    D-3-hydroxyacyl-CoA dehydratase
    D-bifunctional protein, peroxisomal
    peroxisomal multifunctional protein 2
    17-beta-hydroxysteroid dehydrogenase 4
    17beta-estradiol dehydrogenase type IV
    short chain dehydrogenase/reductase family 8C, member 1
    3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase
    NP_000405.1
    NP_001186220.1
    NP_001186221.1
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008182.1 RefSeqGene

      Range
      4991..94883
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000414.3 → NP_000405.1  peroxisomal multifunctional enzyme type 2 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AK312449, BC003098, CX782401, DA508630
      Consensus CDS
      CCDS4126.1
      UniProtKB/TrEMBL
      B2R659
      UniProtKB/Swiss-Prot
      P51659
      Related
      ENSP00000256216, OTTHUMP00000159141, ENST00000256216, OTTHUMT00000250863
      Conserved Domains (5) summary
      cd03448
      Location:485 – 606
      Blast Score: 554
      HDE_HSD; HDE_HSD The R-hydratase-like hot dog fold of the 17-beta-hydroxysteriod dehydrogenase (HSD), and Hydratase-Dehydrogenase-Epimerase (HDE) proteins. Other enzymes with this fold include MaoC dehydratase, and the fatty acid synthase beta subunit.
      PLN02864
      Location:328 – 605
      Blast Score: 660
      PLN02864; enoyl-CoA hydratase
      cd05353
      Location:31 – 254
      Blast Score: 1129
      hydroxyacyl-CoA-like_DH_SDR_c-like; (3R)-hydroxyacyl-CoA dehydrogenase-like, classical(c)-like SDRs
      cl00509
      Location:327 – 457
      Blast Score: 154
      hot_dog; The hotdog fold was initially identified in the E. coli FabA (beta-hydroxydecanoyl-acyl carrier protein (ACP)-dehydratase) structure and subsequently in 4HBT (4-hydroxybenzoyl-CoA thioesterase) from Pseudomonas. A number of other seemingly unrelated ...
      cl01225
      Location:628 – 731
      Blast Score: 230
      SCP2; SCP-2 sterol transfer family

    2. NM_001199291.1 → NP_001186220.1  peroxisomal multifunctional enzyme type 2 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AK298075, BC003098, CX782401, DC325873
      Consensus CDS
      CCDS56379.1
      UniProtKB/TrEMBL
      B4DNV1
      UniProtKB/TrEMBL
      F5HE57
      UniProtKB/Swiss-Prot
      P51659
      Related
      ENSP00000420914, OTTHUMP00000222965, ENST00000504811, OTTHUMT00000371139
      Conserved Domains (5) summary
      cd03448
      Location:510 – 631
      Blast Score: 558
      HDE_HSD; HDE_HSD The R-hydratase-like hot dog fold of the 17-beta-hydroxysteriod dehydrogenase (HSD), and Hydratase-Dehydrogenase-Epimerase (HDE) proteins. Other enzymes with this fold include MaoC dehydratase, and the fatty acid synthase beta subunit.
      PLN02864
      Location:353 – 630
      Blast Score: 660
      PLN02864; enoyl-CoA hydratase
      cd05353
      Location:61 – 279
      Blast Score: 1110
      hydroxyacyl-CoA-like_DH_SDR_c-like; (3R)-hydroxyacyl-CoA dehydrogenase-like, classical(c)-like SDRs
      cl00509
      Location:352 – 482
      Blast Score: 156
      hot_dog; The hotdog fold was initially identified in the E. coli FabA (beta-hydroxydecanoyl-acyl carrier protein (ACP)-dehydratase) structure and subsequently in 4HBT (4-hydroxybenzoyl-CoA thioesterase) from Pseudomonas. A number of other seemingly unrelated ...
      cl01225
      Location:653 – 756
      Blast Score: 234
      SCP2; SCP-2 sterol transfer family

    3. NM_001199292.1 → NP_001186221.1  peroxisomal multifunctional enzyme type 2 isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AK301212, AK312449, BC003098, CX782401, DA508630
      Consensus CDS
      CCDS56378.1
      UniProtKB/TrEMBL
      B2R659
      UniProtKB/TrEMBL
      B4DVS5
      UniProtKB/TrEMBL
      E9PB82
      UniProtKB/Swiss-Prot
      P51659
      Related
      ENSP00000424613, OTTHUMP00000222964, ENST00000515320, OTTHUMT00000371138
      Conserved Domains (6) summary
      cd03448
      Location:467 – 588
      Blast Score: 553
      HDE_HSD; HDE_HSD The R-hydratase-like hot dog fold of the 17-beta-hydroxysteriod dehydrogenase (HSD), and Hydratase-Dehydrogenase-Epimerase (HDE) proteins. Other enzymes with this fold include MaoC dehydratase, and the fatty acid synthase beta subunit.
      PLN02864
      Location:310 – 587
      Blast Score: 660
      PLN02864; enoyl-CoA hydratase
      PRK05653
      Location:6 – 208
      Blast Score: 454
      fabG; 3-ketoacyl-(acyl-carrier-protein) reductase; Validated
      cd05353
      Location:5 – 236
      Blast Score: 1144
      hydroxyacyl-CoA-like_DH_SDR_c-like; (3R)-hydroxyacyl-CoA dehydrogenase-like, classical(c)-like SDRs
      cl00509
      Location:309 – 439
      Blast Score: 154
      hot_dog; The hotdog fold was initially identified in the E. coli FabA (beta-hydroxydecanoyl-acyl carrier protein (ACP)-dehydratase) structure and subsequently in 4HBT (4-hydroxybenzoyl-CoA thioesterase) from Pseudomonas. A number of other seemingly unrelated ...
      cl01225
      Location:610 – 713
      Blast Score: 230
      SCP2; SCP-2 sterol transfer family

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000005.9 Reference GRCh37.p5 Primary Assembly

      Range
      118788138..118878030
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000137.1 Alternate HuRef

      Range
      113983371..114073268
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC024564.4 (36663..126464) None
    genomic AF057720.1 AAD08652.1
    genomic AF057721.1 AAD08652.1
    genomic AF057722.1 AAD08652.1
    genomic AF057723.1 AAD08652.1
    genomic AF057724.1 AAD08652.1
    genomic AF057725.1 AAD08652.1
    genomic AF057726.1 AAD08652.1
    genomic AF057727.1 AAD08652.1
    genomic AF057728.1 AAD08652.1
    genomic AF057729.1 AAD08652.1
    genomic AF057730.1 AAD08652.1
    genomic AF057731.1 AAD08652.1
    genomic AF057732.1 AAD08652.1
    genomic AF057733.1 AAD08652.1
    genomic AF057735.1 AAD08652.1
    genomic AF057736.1 AAD08652.1
    genomic AF057737.1 AAD08652.1
    genomic AF057738.1 AAD08652.1
    genomic AF057739.1 AAD08652.1
    genomic AF057740.1 AAD08652.1
    genomic CH471086.2 EAW48910.1
      EAW48911.1
    genomic Y11393.1 CAA72203.1
    mRNA AK094049.1 BAG52804.1
    mRNA AK293254.1 BAG56786.1
    mRNA AK295440.1 BAG58380.1
    mRNA AK298075.1 BAG60363.1
    mRNA AK299685.1 BAG61592.1
    mRNA AK301212.1 BAG62787.1
    mRNA AK308968.1 None
    mRNA AK312449.1 BAG35356.1
    mRNA BC003098.1 AAH03098.1
    mRNA CX782401.1 None
    mRNA DA296575.1 None
    mRNA DA426062.1 None
    mRNA DA508630.1 None
    mRNA DC325873.1 None
    mRNA X87176.1 CAA60643.1
    other-genetic DQ891866.2 ABM82792.1
    other-genetic DQ895055.2 ABM85981.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P51659.3 GenPept UniProtKB/Swiss-Prot:P51659
    Q59H27 GenPept UniProtKB/TrEMBL:Q59H27
    Q9UBA4 GenPept UniProtKB/TrEMBL:Q9UBA4
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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