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Protein

Peroxisomal multifunctional enzyme type 2

Gene

HSD17B4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Bifunctional enzyme acting on the peroxisomal beta-oxidation pathway for fatty acids. Catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids.2 Publications

Miscellaneous

The protein is found both as a full-length peptide and in a cleaved version.

Catalytic activityi

(R)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH.1 Publication
(24R,25R)-3-alpha,7-alpha,12-alpha,24-tetrahydroxy-5-beta-cholestanoyl-CoA = (24E)-3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA + H2O.1 Publication
(3R)-3-hydroxyacyl-CoA = (2E)-2-enoyl-CoA + H2O.1 Publication

Kineticsi

  1. KM=10 µM for D-3-hydroxy-octanoyl-CoA1 Publication
  2. KM=13 µM for NAD1 Publication
  3. KM=2.7 µM for 3-ketooctanoyl-CoA1 Publication
  4. KM=5.4 µM for NADH1 Publication
  1. Vmax=8.8 µmol/min/mg enzyme1 Publication

Pathwayi: fatty acid beta-oxidation

This protein is involved in the pathway fatty acid beta-oxidation, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway fatty acid beta-oxidation and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei21NAD; via amide nitrogen1
Binding sitei40NAD1
Binding sitei99NAD; via carbonyl oxygen1
Binding sitei151SubstrateBy similarity1
Active sitei164Proton acceptorPROSITE-ProRule annotation1
Binding sitei435(3R)-3-hydroxydecanoyl-CoABy similarity1
Binding sitei533(3R)-3-hydroxydecanoyl-CoA; via amide nitrogenBy similarity1
Binding sitei563(3R)-3-hydroxydecanoyl-CoA; via carbonyl oxygenBy similarity1
Binding sitei706Substrate1
Binding sitei724Substrate1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi13 – 37NADBy similarityAdd BLAST25
Nucleotide bindingi75 – 76NAD2
Nucleotide bindingi164 – 168NAD5
Nucleotide bindingi196 – 199NAD4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIsomerase, Lyase, Oxidoreductase
Biological processFatty acid metabolism, Lipid metabolism
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:HS05792-MONOMER
BRENDAi4.2.1.119 2681
ReactomeiR-HSA-193368 Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-2046106 alpha-linolenic acid (ALA) metabolism
R-HSA-389887 Beta-oxidation of pristanoyl-CoA
R-HSA-390247 Beta-oxidation of very long chain fatty acids
R-HSA-9033241 Peroxisomal protein import
R-HSA-9033500 TYSND1 cleaves peroxisomal proteins
SABIO-RKiP51659
UniPathwayi
UPA00659

Chemistry databases

SwissLipidsiSLP:000000540

Names & Taxonomyi

Protein namesi
Recommended name:
Peroxisomal multifunctional enzyme type 2
Short name:
MFE-2
Alternative name(s):
17-beta-hydroxysteroid dehydrogenase 4
Short name:
17-beta-HSD 4
D-bifunctional protein
Short name:
DBP
Multifunctional protein 2
Short name:
MPF-2
Short chain dehydrogenase/reductase family 8C member 1
Cleaved into the following 2 chains:
Alternative name(s):
3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase
Gene namesi
Name:HSD17B4
Synonyms:EDH17B4, SDR8C1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000133835.14
HGNCiHGNC:5213 HSD17B4
MIMi601860 gene
neXtProtiNX_P51659

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Peroxisome

Pathology & Biotechi

Involvement in diseasei

D-bifunctional protein deficiency (DBPD)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionDisorder of peroxisomal fatty acid beta-oxidation.
See also OMIM:261515
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03757616G → S in DBPD; no dehydrogenase activity. 2 PublicationsCorresponds to variant dbSNP:rs137853096EnsemblClinVar.1
Natural variantiVAR_065906106R → P in DBPD. 1 PublicationCorresponds to variant dbSNP:rs25640EnsemblClinVar.1
Natural variantiVAR_065908457N → Y in DBPD; the mutation leads to an unstable protein. 1 PublicationCorresponds to variant dbSNP:rs137853097EnsemblClinVar.1
Perrault syndrome 1 (PRLTS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild mental retardation and cerebellar and peripheral nervous system involvement.
See also OMIM:233400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065907217Y → C in PRLTS1. 1 PublicationCorresponds to variant dbSNP:rs387906825EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi347Y → A: No hydratase activity. 1 Publication1
Mutagenesisi366E → A: No hydratase activity. 1 Publication1
Mutagenesisi370D → A: No effect. 1 Publication1
Mutagenesisi406H → A: No effect. 1 Publication1
Mutagenesisi408E → A: No effect. 1 Publication1
Mutagenesisi410Y → A: No effect. 1 Publication1
Mutagenesisi490D → A: No effect. 1 Publication1
Mutagenesisi505Y → A: Completely inactive. 1 Publication1
Mutagenesisi510D → A: No hydratase activity. 1 Publication1
Mutagenesisi515H → A: Completely inactive. 1 Publication1
Mutagenesisi517D → A: No effect. 1 Publication1
Mutagenesisi532H → A: No effect. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation

Organism-specific databases

DisGeNETi3295
MalaCardsiHSD17B4
MIMi233400 phenotype
261515 phenotype
OpenTargetsiENSG00000133835
Orphaneti300 Bifunctional enzyme deficiency
2855 Perrault syndrome
PharmGKBiPA29481

Chemistry databases

ChEMBLiCHEMBL5814
DrugBankiDB03192 3r-Hydroxydecanoyl-Coa
DB00157 NADH

Polymorphism and mutation databases

BioMutaiHSD17B4
DMDMi1706396

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000545831 – 736Peroxisomal multifunctional enzyme type 2Add BLAST736
ChainiPRO_00004000821 – 311(3R)-hydroxyacyl-CoA dehydrogenaseAdd BLAST311
ChainiPRO_0000400083312 – 736Enoyl-CoA hydratase 2Add BLAST425

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei46N6-acetyllysine; alternateBy similarity1
Modified residuei46N6-succinyllysine; alternateBy similarity1
Modified residuei52PhosphoserineCombined sources1
Modified residuei57N6-succinyllysineBy similarity1
Modified residuei68N6-succinyllysineBy similarity1
Modified residuei84N6-succinyllysineBy similarity1
Modified residuei265PhosphothreonineCombined sources1
Modified residuei275N6-succinyllysineBy similarity1
Modified residuei304PhosphoserineCombined sources1
Modified residuei309PhosphoserineCombined sources1
Modified residuei356N6-succinyllysineBy similarity1
Modified residuei424N6-succinyllysineBy similarity1
Modified residuei565N6-acetyllysineCombined sources1
Modified residuei579N6-succinyllysineBy similarity1
Modified residuei663N6-succinyllysineBy similarity1
Modified residuei669N6-acetyllysineCombined sources1
Modified residuei707N6-acetyllysineCombined sources1
Modified residuei725N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP51659
MaxQBiP51659
PaxDbiP51659
PeptideAtlasiP51659
PRIDEiP51659
ProteomicsDBi56360
TopDownProteomicsiP51659-1 [P51659-1]

PTM databases

iPTMnetiP51659
PhosphoSitePlusiP51659
SwissPalmiP51659

Expressioni

Tissue specificityi

Present in many tissues with highest concentrations in liver, heart, prostate and testis.

Gene expression databases

BgeeiENSG00000133835 Expressed in 233 organ(s), highest expression level in corpus callosum
CleanExiHS_HSD17B4
ExpressionAtlasiP51659 baseline and differential
GenevisibleiP51659 HS

Organism-specific databases

HPAiHPA021302
HPA021311
HPA021479

Interactioni

Subunit structurei

Homodimer.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109528, 49 interactors
IntActiP51659, 40 interactors
MINTiP51659
STRINGi9606.ENSP00000420914

Structurei

Secondary structure

1736
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP51659
SMRiP51659
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51659

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini484 – 600MaoC-likeAdd BLAST117
Domaini624 – 736SCP2Add BLAST113

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 305(3R)-hydroxyacyl-CoA dehydrogenaseAdd BLAST305
Regioni322 – 622Enoyl-CoA hydratase 2Add BLAST301
Regioni406 – 407(3R)-3-hydroxydecanoyl-CoA bindingBy similarity2
Regioni510 – 515(3R)-3-hydroxydecanoyl-CoA bindingBy similarity6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi734 – 736Microbody targeting signalSequence analysis3

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1206 Eukaryota
COG2030 LUCA
GeneTreeiENSGT00530000062928
HOGENOMiHOG000170895
HOVERGENiHBG002174
InParanoidiP51659
KOiK12405
OMAiSRMTQTV
OrthoDBiEOG091G02S9
PhylomeDBiP51659
TreeFamiTF105656

Family and domain databases

Gene3Di3.30.1050.10, 1 hit
InterProiView protein in InterPro
IPR029069 HotDog_dom_sf
IPR002539 MaoC_dom
IPR036291 NAD(P)-bd_dom_sf
IPR020904 Sc_DH/Rdtase_CS
IPR003033 SCP2_sterol-bd_dom
IPR036527 SCP2_sterol-bd_dom_sf
IPR002347 SDR_fam
PfamiView protein in Pfam
PF00106 adh_short, 1 hit
PF01575 MaoC_dehydratas, 1 hit
PF02036 SCP2, 1 hit
PRINTSiPR00081 GDHRDH
PR00080 SDRFAMILY
SUPFAMiSSF51735 SSF51735, 1 hit
SSF54637 SSF54637, 2 hits
SSF55718 SSF55718, 1 hit
PROSITEiView protein in PROSITE
PS00061 ADH_SHORT, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 14 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: P51659-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGSPLRFDGR VVLVTGAGAG LGRAYALAFA ERGALVVVND LGGDFKGVGK
60 70 80 90 100
GSLAADKVVE EIRRRGGKAV ANYDSVEEGE KVVKTALDAF GRIDVVVNNA
110 120 130 140 150
GILRDRSFAR ISDEDWDIIH RVHLRGSFQV TRAAWEHMKK QKYGRIIMTS
160 170 180 190 200
SASGIYGNFG QANYSAAKLG LLGLANSLAI EGRKSNIHCN TIAPNAGSRM
210 220 230 240 250
TQTVMPEDLV EALKPEYVAP LVLWLCHESC EENGGLFEVG AGWIGKLRWE
260 270 280 290 300
RTLGAIVRQK NHPMTPEAVK ANWKKICDFE NASKPQSIQE STGSIIEVLS
310 320 330 340 350
KIDSEGGVSA NHTSRATSTA TSGFAGAIGQ KLPPFSYAYT ELEAIMYALG
360 370 380 390 400
VGASIKDPKD LKFIYEGSSD FSCLPTFGVI IGQKSMMGGG LAEIPGLSIN
410 420 430 440 450
FAKVLHGEQY LELYKPLPRA GKLKCEAVVA DVLDKGSGVV IIMDVYSYSE
460 470 480 490 500
KELICHNQFS LFLVGSGGFG GKRTSDKVKV AVAIPNRPPD AVLTDTTSLN
510 520 530 540 550
QAALYRLSGD WNPLHIDPNF ASLAGFDKPI LHGLCTFGFS ARRVLQQFAD
560 570 580 590 600
NDVSRFKAIK ARFAKPVYPG QTLQTEMWKE GNRIHFQTKV QETGDIVISN
610 620 630 640 650
AYVDLAPTSG TSAKTPSEGG KLQSTFVFEE IGRRLKDIGP EVVKKVNAVF
660 670 680 690 700
EWHITKGGNI GAKWTIDLKS GSGKVYQGPA KGAADTTIIL SDEDFMEVVL
710 720 730
GKLDPQKAFF SGRLKARGNI MLSQKLQMIL KDYAKL
Length:736
Mass (Da):79,686
Last modified:January 23, 2007 - v3
Checksum:i7B11E02483328BCE
GO
Isoform 2 (identifier: P51659-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MGSPLRFDGR...FAERGALVVV → MVILEAPHLL...ISQCRFFVSM

Note: No experimental confirmation available.
Show »
Length:761
Mass (Da):83,025
Checksum:i246D60646BD2C7A8
GO
Isoform 3 (identifier: P51659-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     20-37: Missing.

Note: No experimental confirmation available.
Show »
Length:718
Mass (Da):77,870
Checksum:i79C506BC0D73B5C2
GO

Computationally mapped potential isoform sequencesi

There are 14 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G5E9S2G5E9S2_HUMAN
Hydroxysteroid (17-beta) dehydrogen...
HSD17B4 hCG_37330
596Annotation score:
E7EWE5E7EWE5_HUMAN
Peroxisomal multifunctional enzyme ...
HSD17B4
712Annotation score:
E7ET17E7ET17_HUMAN
Peroxisomal multifunctional enzyme ...
HSD17B4
599Annotation score:
E7ER27E7ER27_HUMAN
Peroxisomal multifunctional enzyme ...
HSD17B4
500Annotation score:
A0A2R8YD50A0A2R8YD50_HUMAN
Peroxisomal multifunctional enzyme ...
HSD17B4
711Annotation score:
A0A2R8Y7L2A0A2R8Y7L2_HUMAN
Peroxisomal multifunctional enzyme ...
HSD17B4
589Annotation score:
A0A2R8Y7W2A0A2R8Y7W2_HUMAN
Peroxisomal multifunctional enzyme ...
HSD17B4
105Annotation score:
E7EPL9E7EPL9_HUMAN
Peroxisomal multifunctional enzyme ...
HSD17B4
474Annotation score:
A0A2R8YF39A0A2R8YF39_HUMAN
Peroxisomal multifunctional enzyme ...
HSD17B4
50Annotation score:
A0A2R8YDT8A0A2R8YDT8_HUMAN
Peroxisomal multifunctional enzyme ...
HSD17B4
166Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti587Q → R in BAG60363 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03757616G → S in DBPD; no dehydrogenase activity. 2 PublicationsCorresponds to variant dbSNP:rs137853096EnsemblClinVar.1
Natural variantiVAR_05230990F → L. Corresponds to variant dbSNP:rs28943588EnsemblClinVar.1
Natural variantiVAR_014872106R → H2 PublicationsCorresponds to variant dbSNP:rs25640EnsemblClinVar.1
Natural variantiVAR_065906106R → P in DBPD. 1 PublicationCorresponds to variant dbSNP:rs25640EnsemblClinVar.1
Natural variantiVAR_052310140K → N. Corresponds to variant dbSNP:rs28943589EnsemblClinVar.1
Natural variantiVAR_065907217Y → C in PRLTS1. 1 PublicationCorresponds to variant dbSNP:rs387906825EnsemblClinVar.1
Natural variantiVAR_024625292T → S. Corresponds to variant dbSNP:rs1143650EnsemblClinVar.1
Natural variantiVAR_052311427A → V. Corresponds to variant dbSNP:rs28943590EnsemblClinVar.1
Natural variantiVAR_065908457N → Y in DBPD; the mutation leads to an unstable protein. 1 PublicationCorresponds to variant dbSNP:rs137853097EnsemblClinVar.1
Natural variantiVAR_052312491A → T. Corresponds to variant dbSNP:rs28943591EnsemblClinVar.1
Natural variantiVAR_014873511W → R1 PublicationCorresponds to variant dbSNP:rs11539471EnsemblClinVar.1
Natural variantiVAR_014874559I → V2 PublicationsCorresponds to variant dbSNP:rs11205EnsemblClinVar.1
Natural variantiVAR_052313606A → S. Corresponds to variant dbSNP:rs15228Ensembl.1
Natural variantiVAR_052314687T → I. Corresponds to variant dbSNP:rs28943592EnsemblClinVar.1
Natural variantiVAR_052315728M → V. Corresponds to variant dbSNP:rs28943594EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0461521 – 38MGSPL…ALVVV → MVILEAPHLLRRKEPETPGL SSRIGPSLCPGFCRKRSVSC CFQNLCNNPMEKIISQCRFF VSM in isoform 2. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_04615320 – 37Missing in isoform 3. 1 PublicationAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X87176 mRNA Translation: CAA60643.1
AF057740
, AF057720, AF057721, AF057722, AF057723, AF057724, AF057725, AF057726, AF057727, AF057728, AF057729, AF057730, AF057731, AF057732, AF057733, AF057734, AF057735, AF057736, AF057737, AF057738, AF057739 Genomic DNA Translation: AAD08652.1
AK298075 mRNA Translation: BAG60363.1
AK301212 mRNA Translation: BAG62787.1
AC024564 Genomic DNA No translation available.
BC003098 mRNA Translation: AAH03098.1
CCDSiCCDS4126.1 [P51659-1]
CCDS56378.1 [P51659-3]
CCDS56379.1 [P51659-2]
PIRiS59136
RefSeqiNP_000405.1, NM_000414.3 [P51659-1]
NP_001186220.1, NM_001199291.2 [P51659-2]
NP_001186221.1, NM_001199292.1 [P51659-3]
NP_001278956.1, NM_001292027.1
NP_001278957.1, NM_001292028.1
UniGeneiHs.406861

Genome annotation databases

EnsembliENST00000256216; ENSP00000256216; ENSG00000133835 [P51659-1]
ENST00000414835; ENSP00000411960; ENSG00000133835 [P51659-2]
ENST00000504811; ENSP00000420914; ENSG00000133835 [P51659-2]
ENST00000510025; ENSP00000424940; ENSG00000133835 [P51659-1]
ENST00000515320; ENSP00000424613; ENSG00000133835 [P51659-3]
GeneIDi3295
KEGGihsa:3295
UCSCiuc003ksj.4 human [P51659-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDHB4_HUMAN
AccessioniPrimary (citable) accession number: P51659
Secondary accession number(s): B4DNV1
, B4DVS5, E9PB82, F5HE57
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 196 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health

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