Hsd17b4 hydroxysteroid (17-beta) dehydrogenase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hsd17b4provided by MGI
Official Full Name: hydroxysteroid (17-beta) dehydrogenase 4provided by MGI
Primary source: MGI:MGI:105089
See related: Ensembl:ENSMUSG00000024507 AllianceGenome:MGI:105089
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: DBP; MFP2; MFE-2; MPF-2; Mfp-2; perMFE-2; 17[b]-HSD; 17-beta-HSD
Summary: Predicted to enable hydro-lyase activity; oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; and protein homodimerization activity. Acts upstream of or within Sertoli cell development; fatty acid beta-oxidation; and very long-chain fatty acid metabolic process. Located in peroxisome. Is expressed in several structures, including brain; genitourinary system; hindlimb phalanx; integumental system; and jaw. Used to study D-bifunctional protein deficiency. Human ortholog(s) of this gene implicated in D-bifunctional protein deficiency; Perrault syndrome; and Stiff-Person syndrome. Orthologous to human HSD17B4 (hydroxysteroid 17-beta dehydrogenase 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in liver adult (RPKM 28.9), placenta adult (RPKM 27.7) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 18 D1; 18 27.24 cM

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	18	NC_000084.7 (50261268..50329337)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	18	NC_000084.6 (50128201..50196270)

Chromosome 18 - NC_000084.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Peroxisomal Localization of Hsd17b4 Is Regulated by Its Interaction with Phosphatidylserine.
Title: The Peroxisomal Localization of Hsd17b4 Is Regulated by Its Interaction with Phosphatidylserine.
The D-bifunctional protein (HSD17B4) and the peroxisomal ABC transporter ABCD3 are essential in peroxisomal oxidation of lauric and palmitic acid.
Title: Peroxisomes can oxidize medium- and long-chain fatty acids through a pathway involving ABCD3 and HSD17B4.
Association of Hsd17b4 with ceramide-enriched mitochondria-associated membranes prevents its interaction with peroxisomal import protein Pex5 at peroxisomes.
Title: Ceramide regulates interaction of Hsd17b4 with Pex5 and function of peroxisomes.
This study demonstrated that MFP2 deficiency in microglia causes intrinsic dysregulation of their inflammatory profile, which is not harmful to neuronal function, motor function, and cognition in mice during their first year of life
Title: Microglia lacking a peroxisomal β-oxidation enzyme chronically alter their inflammatory profile without evoking neuronal and behavioral deficits.
Nestin-Mfp2(-/-) mice showed impaired motor learning on the accelerating rotarod and underperformed on the balance beam test
Title: Early-onset Purkinje cell dysfunction underlies cerebellar ataxia in peroxisomal multifunctional protein-2 deficiency.
Study showed that the resident microglia in Mfp2-/- mice proliferate, are permanently in an activated nonphagocytic state and lose their typical homeostatic markers
Title: Identification of a chronic non-neurodegenerative microglia activation state in a mouse model of peroxisomal β-oxidation deficiency.
Peroxisomal multifunctional protein-2 deficiency causes neuroinflammation and degeneration of Purkinje cells independent of very long chain fatty acid accumulation in mice.
Title: Peroxisomal multifunctional protein-2 deficiency causes neuroinflammation and degeneration of Purkinje cells independent of very long chain fatty acid accumulation.
Loss of MFP2 leads to attenuation of up-regulations of SREBP2 and HMGCR involved in cholesterol synthesis.
Title: Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice.
MFP-2 is important for the normal functioning of the brain, eyes and testis
Title: Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model.
bile acid biosynthesis, estimated by the ratio of C27/C24-bile acids, is more severely affected in double knock-out mice as compared with DBP-/- mice but was normal in LBP-/- mice
Title: Developmental changes of bile acid composition and conjugation in L- and D-bifunctional protein single and double knockout mice.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (2) 1 citation
Endonuclease-mediated (5)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Hsd17b4 (e-PCR), detects polymorphism
- UniSTS:546823

RH126796 (e-PCR)
- UniSTS:209741

RH125938 (e-PCR)
- UniSTS:162650

RH139213 (e-PCR)
- UniSTS:221299

AW208803 (e-PCR)
- UniSTS:181120

NoName (e-PCR)
- UniSTS:224400

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables (3R)-hydroxyacyl-CoA dehydrogenase (NAD+) activity	IEA Inferred from Electronic Annotation more info
enables 17-beta-hydroxysteroid dehydrogenase (NAD+) activity	IBA Inferred from Biological aspect of Ancestor more info
enables 17-beta-hydroxysteroid dehydrogenase (NAD+) activity	ISO Inferred from Sequence Orthology more info
enables 3-hydroxyacyl-CoA dehydratase activity	ISO Inferred from Sequence Orthology more info
enables 3-hydroxyacyl-CoA dehydrogenase activity	IBA Inferred from Biological aspect of Ancestor more info
enables 3-hydroxyacyl-CoA dehydrogenase activity	ISO Inferred from Sequence Orthology more info
enables 3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity	IEA Inferred from Electronic Annotation more info
enables enoyl-CoA hydratase activity	IBA Inferred from Biological aspect of Ancestor more info
enables enoyl-CoA hydratase activity	ISO Inferred from Sequence Orthology more info
enables estradiol 17-beta-dehydrogenase [NAD(P)] activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables isomerase activity	IEA Inferred from Electronic Annotation more info
enables lyase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within Sertoli cell development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in androgen metabolic process	ISO Inferred from Sequence Orthology more info
involved_in estrogen metabolic process	ISO Inferred from Sequence Orthology more info
involved_in fatty acid beta-oxidation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within fatty acid beta-oxidation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in fatty acid beta-oxidation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within fatty acid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in medium-chain fatty-acyl-CoA metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within very long-chain fatty acid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in very long-chain fatty-acyl-CoA metabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in mitochondrion	HDA more info	PubMed
located_in peroxisomal matrix	TAS Traceable Author Statement more info
is_active_in peroxisome	IBA Inferred from Biological aspect of Ancestor more info
located_in peroxisome	IDA Inferred from Direct Assay more info	PubMed
located_in peroxisome	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: peroxisomal multifunctional enzyme type 2

Names: 17-beta-HSD 4; 17-beta-hydroxysteroid dehydrogenase 4; D-bifunctional protein; multifunctional protein 2

NP_032318.2

EC 1.1.1.n12

EC 4.2.1.107

EC 4.2.1.119

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_008292.4 → NP_032318.2 peroxisomal multifunctional enzyme type 2

See identical proteins and their annotated locations for NP_032318.2

Status: VALIDATED

Source sequence(s)

AC118632, AK004866

Consensus CDS

CCDS29242.1

UniProtKB/Swiss-Prot

P51660, Q9DBM3

UniProtKB/TrEMBL

Q3TT11, Q3UHW2

Related

ENSMUSP00000025385.7, ENSMUST00000025385.7

Conserved Domains (6) summary

PLN02864
Location:329 → 604

PLN02864; enoyl-CoA hydratase

cd05353
Location:5 → 254

hydroxyacyl-CoA-like_DH_SDR_c-like; (3R)-hydroxyacyl-CoA dehydrogenase-like, classical(c)-like SDRs

PRK05653
Location:6 → 226

fabG; 3-ketoacyl-(acyl-carrier-protein) reductase; Validated

cd03448
Location:484 → 604

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.

pfam02036
Location:633 → 730

SCP2; SCP-2 sterol transfer family

cl00509
Location:394 → 443

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 ...