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P51659

- DHB4_HUMAN

UniProt

P51659 - DHB4_HUMAN

Protein

Peroxisomal multifunctional enzyme type 2

Gene

HSD17B4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 158 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    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

    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

    Vmax=8.8 µmol/min/mg enzyme1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei21 – 211NAD; via amide nitrogen
    Binding sitei40 – 401NAD
    Binding sitei99 – 991NAD; via carbonyl oxygen
    Binding sitei151 – 1511SubstrateBy similarity
    Active sitei164 – 1641Proton acceptorPROSITE-ProRule annotation
    Binding sitei435 – 4351(3R)-3-hydroxydecanoyl-CoABy similarity
    Binding sitei533 – 5331(3R)-3-hydroxydecanoyl-CoA; via amide nitrogenBy similarity
    Binding sitei563 – 5631(3R)-3-hydroxydecanoyl-CoA; via carbonyl oxygenBy similarity
    Binding sitei706 – 7061Substrate
    Binding sitei724 – 7241Substrate

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi13 – 3725NADBy similarityAdd
    BLAST
    Nucleotide bindingi75 – 762NAD
    Nucleotide bindingi164 – 1685NAD
    Nucleotide bindingi196 – 1994NAD

    GO - Molecular functioni

    1. 17-beta-hydroxysteroid dehydrogenase (NAD+) activity Source: UniProtKB
    2. 3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity Source: Reactome
    3. 3-hydroxyacyl-CoA dehydrogenase activity Source: UniProtKB
    4. isomerase activity Source: UniProtKB-KW
    5. long-chain-enoyl-CoA hydratase activity Source: UniProtKB
    6. protein homodimerization activity Source: UniProtKB
    7. receptor binding Source: UniProtKB

    GO - Biological processi

    1. alpha-linolenic acid metabolic process Source: Reactome
    2. androgen metabolic process Source: UniProtKB
    3. bile acid biosynthetic process Source: Reactome
    4. bile acid metabolic process Source: Reactome
    5. cellular lipid metabolic process Source: Reactome
    6. estrogen metabolic process Source: UniProtKB
    7. fatty acid beta-oxidation Source: UniProtKB
    8. fatty acid beta-oxidation using acyl-CoA oxidase Source: Reactome
    9. medium-chain fatty-acyl-CoA metabolic process Source: UniProtKB
    10. metabolic process Source: GOC
    11. osteoblast differentiation Source: UniProt
    12. oxidation-reduction process Source: GOC
    13. Sertoli cell development Source: Ensembl
    14. small molecule metabolic process Source: Reactome
    15. unsaturated fatty acid metabolic process Source: Reactome
    16. very long-chain fatty acid metabolic process Source: Ensembl
    17. very long-chain fatty-acyl-CoA metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Isomerase, Lyase, Oxidoreductase

    Keywords - Biological processi

    Fatty acid metabolism, Lipid metabolism

    Keywords - Ligandi

    NAD

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05792-MONOMER.
    ReactomeiREACT_11041. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
    REACT_121147. alpha-linolenic acid (ALA) metabolism.
    REACT_17017. Beta-oxidation of pristanoyl-CoA.
    REACT_17062. Beta-oxidation of very long chain fatty acids.
    SABIO-RKP51659.
    UniPathwayiUPA00659.

    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
    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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:5213. HSD17B4.

    Subcellular locationi

    GO - Cellular componenti

    1. intracellular membrane-bounded organelle Source: HPA
    2. membrane Source: UniProt
    3. mitochondrion Source: Ensembl
    4. peroxisomal matrix Source: Reactome
    5. peroxisomal membrane Source: UniProtKB
    6. peroxisome Source: UniProtKB

    Keywords - Cellular componenti

    Peroxisome

    Pathology & Biotechi

    Involvement in diseasei

    D-bifunctional protein deficiency (DBPD) [MIM:261515]: Disorder of peroxisomal fatty acid beta-oxidation.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti16 – 161G → S in DBPD. 1 Publication
    VAR_037576
    Natural varianti106 – 1061R → P in DBPD. 1 Publication
    Corresponds to variant rs25640 [ dbSNP | Ensembl ].
    VAR_065906
    Natural varianti457 – 4571N → Y in DBPD; the mutation leads to an unstable protein. 1 Publication
    VAR_065908
    Perrault syndrome 1 (PRLTS1) [MIM:233400]: A 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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti217 – 2171Y → C in PRLTS1. 1 Publication
    VAR_065907

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi16 – 161G → S: No dehydrogenase activity. 1 Publication
    Mutagenesisi347 – 3471Y → A: No hydratase activity. 1 Publication
    Mutagenesisi366 – 3661E → A: No hydratase activity. 1 Publication
    Mutagenesisi370 – 3701D → A: No effect. 1 Publication
    Mutagenesisi406 – 4061H → A: No effect. 1 Publication
    Mutagenesisi408 – 4081E → A: No effect. 1 Publication
    Mutagenesisi410 – 4101Y → A: No effect. 1 Publication
    Mutagenesisi490 – 4901D → A: No effect. 1 Publication
    Mutagenesisi505 – 5051Y → A: Completely inactive. 1 Publication
    Mutagenesisi510 – 5101D → A: No hydratase activity. 1 Publication
    Mutagenesisi515 – 5151H → A: Completely inactive. 1 Publication
    Mutagenesisi517 – 5171D → A: No effect. 1 Publication
    Mutagenesisi532 – 5321H → A: No effect. 1 Publication

    Keywords - Diseasei

    Deafness, Disease mutation

    Organism-specific databases

    MIMi233400. phenotype.
    261515. phenotype.
    Orphaneti300. Bifunctional enzyme deficiency.
    2855. Perrault syndrome.
    PharmGKBiPA29481.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 736736Peroxisomal multifunctional enzyme type 2PRO_0000054583Add
    BLAST
    Chaini1 – 311311(3R)-hydroxyacyl-CoA dehydrogenasePRO_0000400082Add
    BLAST
    Chaini312 – 736425Enoyl-CoA hydratase 2PRO_0000400083Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei46 – 461N6-acetyllysine; alternateBy similarity
    Modified residuei46 – 461N6-succinyllysine; alternateBy similarity
    Modified residuei57 – 571N6-succinyllysineBy similarity
    Modified residuei68 – 681N6-succinyllysineBy similarity
    Modified residuei84 – 841N6-succinyllysineBy similarity
    Modified residuei275 – 2751N6-succinyllysineBy similarity
    Modified residuei304 – 3041Phosphoserine1 Publication
    Modified residuei309 – 3091Phosphoserine1 Publication
    Modified residuei356 – 3561N6-succinyllysineBy similarity
    Modified residuei424 – 4241N6-succinyllysineBy similarity
    Modified residuei565 – 5651N6-acetyllysine1 Publication
    Modified residuei579 – 5791N6-succinyllysineBy similarity
    Modified residuei663 – 6631N6-succinyllysineBy similarity
    Modified residuei669 – 6691N6-acetyllysine1 Publication
    Modified residuei707 – 7071N6-acetyllysine1 Publication
    Modified residuei725 – 7251N6-succinyllysineBy similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP51659.
    PaxDbiP51659.
    PeptideAtlasiP51659.
    PRIDEiP51659.

    PTM databases

    PhosphoSiteiP51659.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    ArrayExpressiP51659.
    BgeeiP51659.
    CleanExiHS_HSD17B4.
    GenevestigatoriP51659.

    Organism-specific databases

    HPAiHPA021302.
    HPA021311.
    HPA021479.

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Protein-protein interaction databases

    BioGridi109528. 25 interactions.
    IntActiP51659. 16 interactions.
    MINTiMINT-1135639.
    STRINGi9606.ENSP00000256216.

    Structurei

    Secondary structure

    1
    736
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi11 – 144
    Turni15 – 184
    Helixi20 – 3112
    Beta strandi35 – 395
    Helixi53 – 6412
    Beta strandi68 – 725
    Helixi76 – 783
    Helixi79 – 9012
    Beta strandi95 – 984
    Helixi108 – 1103
    Helixi113 – 14129
    Beta strandi144 – 1496
    Helixi152 – 1565
    Helixi162 – 18221
    Helixi183 – 1853
    Beta strandi187 – 1948
    Turni199 – 2046
    Helixi207 – 2126
    Helixi215 – 2173
    Helixi219 – 2257
    Beta strandi236 – 2405
    Beta strandi243 – 2519
    Helixi266 – 2716
    Helixi273 – 2775
    Helixi288 – 30316
    Beta strandi335 – 3395
    Helixi341 – 35010
    Helixi358 – 3603
    Helixi361 – 3644
    Helixi375 – 3773
    Helixi378 – 3814
    Helixi383 – 3853
    Beta strandi405 – 41511
    Beta strandi419 – 43214
    Beta strandi440 – 46223
    Beta strandi490 – 4967
    Helixi501 – 5055
    Helixi506 – 5083
    Helixi513 – 5153
    Helixi518 – 5225
    Turni523 – 5253
    Helixi533 – 54816
    Helixi553 – 5553
    Beta strandi556 – 5638
    Beta strandi572 – 5809
    Beta strandi583 – 5908
    Turni591 – 5933
    Beta strandi596 – 60510
    Helixi624 – 64623
    Beta strandi648 – 67023
    Beta strandi674 – 6796
    Beta strandi685 – 6917
    Helixi692 – 6998
    Helixi705 – 7106
    Beta strandi713 – 7197
    Helixi720 – 73314

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IKTX-ray1.75A618-736[»]
    1S9CX-ray3.00A/B/C/D/E/F/G/H/I/J/K/L318-615[»]
    1ZBQX-ray2.71A/B/C/D/E/F1-304[»]
    ProteinModelPortaliP51659.
    SMRiP51659. Positions 3-304, 323-606, 622-736.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP51659.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini484 – 600117MaoC-likeAdd
    BLAST
    Domaini624 – 736113SCP2Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 305305(3R)-hydroxyacyl-CoA dehydrogenaseAdd
    BLAST
    Regioni322 – 622301Enoyl-CoA hydratase 2Add
    BLAST
    Regioni406 – 4072(3R)-3-hydroxydecanoyl-CoA bindingBy similarity
    Regioni510 – 5156(3R)-3-hydroxydecanoyl-CoA bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi734 – 7363Microbody targeting signalSequence Analysis

    Sequence similaritiesi

    Contains 1 MaoC-like domain.Curated
    Contains 1 SCP2 domain.Curated

    Phylogenomic databases

    eggNOGiCOG1028.
    HOGENOMiHOG000170895.
    HOVERGENiHBG002174.
    InParanoidiP51659.
    KOiK12405.
    OMAiCHESCED.
    OrthoDBiEOG7RBZ7V.
    PhylomeDBiP51659.
    TreeFamiTF105656.

    Family and domain databases

    Gene3Di3.10.129.10. 2 hits.
    3.30.1050.10. 1 hit.
    3.40.50.720. 1 hit.
    InterProiIPR002198. DH_sc/Rdtase_SDR.
    IPR002347. Glc/ribitol_DH.
    IPR029069. HotDog_dom.
    IPR002539. MaoC_dom.
    IPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    IPR003033. SCP2_sterol-bd_dom.
    [Graphical view]
    PfamiPF00106. adh_short. 1 hit.
    PF01575. MaoC_dehydratas. 1 hit.
    PF02036. SCP2. 1 hit.
    [Graphical view]
    PRINTSiPR00081. GDHRDH.
    PR00080. SDRFAMILY.
    SUPFAMiSSF54637. SSF54637. 2 hits.
    SSF55718. SSF55718. 1 hit.
    PROSITEiPS00061. ADH_SHORT. 1 hit.
    [Graphical view]

    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. Align

    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

    MGSPLRFDGR VVLVTGAGAG LGRAYALAFA ERGALVVVND LGGDFKGVGK    50
    GSLAADKVVE EIRRRGGKAV ANYDSVEEGE KVVKTALDAF GRIDVVVNNA 100
    GILRDRSFAR ISDEDWDIIH RVHLRGSFQV TRAAWEHMKK QKYGRIIMTS 150
    SASGIYGNFG QANYSAAKLG LLGLANSLAI EGRKSNIHCN TIAPNAGSRM 200
    TQTVMPEDLV EALKPEYVAP LVLWLCHESC EENGGLFEVG AGWIGKLRWE 250
    RTLGAIVRQK NHPMTPEAVK ANWKKICDFE NASKPQSIQE STGSIIEVLS 300
    KIDSEGGVSA NHTSRATSTA TSGFAGAIGQ KLPPFSYAYT ELEAIMYALG 350
    VGASIKDPKD LKFIYEGSSD FSCLPTFGVI IGQKSMMGGG LAEIPGLSIN 400
    FAKVLHGEQY LELYKPLPRA GKLKCEAVVA DVLDKGSGVV IIMDVYSYSE 450
    KELICHNQFS LFLVGSGGFG GKRTSDKVKV AVAIPNRPPD AVLTDTTSLN 500
    QAALYRLSGD WNPLHIDPNF ASLAGFDKPI LHGLCTFGFS ARRVLQQFAD 550
    NDVSRFKAIK ARFAKPVYPG QTLQTEMWKE GNRIHFQTKV QETGDIVISN 600
    AYVDLAPTSG TSAKTPSEGG KLQSTFVFEE IGRRLKDIGP EVVKKVNAVF 650
    EWHITKGGNI GAKWTIDLKS GSGKVYQGPA KGAADTTIIL SDEDFMEVVL 700
    GKLDPQKAFF SGRLKARGNI MLSQKLQMIL KDYAKL 736
    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti587 – 5871Q → R in BAG60363. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti16 – 161G → S in DBPD. 1 Publication
    VAR_037576
    Natural varianti90 – 901F → L.
    Corresponds to variant rs28943588 [ dbSNP | Ensembl ].
    VAR_052309
    Natural varianti106 – 1061R → H.1 Publication
    Corresponds to variant rs25640 [ dbSNP | Ensembl ].
    VAR_014872
    Natural varianti106 – 1061R → P in DBPD. 1 Publication
    Corresponds to variant rs25640 [ dbSNP | Ensembl ].
    VAR_065906
    Natural varianti140 – 1401K → N.
    Corresponds to variant rs28943589 [ dbSNP | Ensembl ].
    VAR_052310
    Natural varianti217 – 2171Y → C in PRLTS1. 1 Publication
    VAR_065907
    Natural varianti292 – 2921T → S.
    Corresponds to variant rs1143650 [ dbSNP | Ensembl ].
    VAR_024625
    Natural varianti427 – 4271A → V.
    Corresponds to variant rs28943590 [ dbSNP | Ensembl ].
    VAR_052311
    Natural varianti457 – 4571N → Y in DBPD; the mutation leads to an unstable protein. 1 Publication
    VAR_065908
    Natural varianti491 – 4911A → T.
    Corresponds to variant rs28943591 [ dbSNP | Ensembl ].
    VAR_052312
    Natural varianti511 – 5111W → R.1 Publication
    Corresponds to variant rs11539471 [ dbSNP | Ensembl ].
    VAR_014873
    Natural varianti559 – 5591I → V.1 Publication
    Corresponds to variant rs11205 [ dbSNP | Ensembl ].
    VAR_014874
    Natural varianti606 – 6061A → S.
    Corresponds to variant rs15228 [ dbSNP | Ensembl ].
    VAR_052313
    Natural varianti687 – 6871T → I.
    Corresponds to variant rs28943592 [ dbSNP | Ensembl ].
    VAR_052314
    Natural varianti728 – 7281M → V.
    Corresponds to variant rs28943594 [ dbSNP | Ensembl ].
    VAR_052315

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 3838MGSPL…ALVVV → MVILEAPHLLRRKEPETPGL SSRIGPSLCPGFCRKRSVSC CFQNLCNNPMEKIISQCRFF VSM in isoform 2. 1 PublicationVSP_046152Add
    BLAST
    Alternative sequencei20 – 3718Missing in isoform 3. 1 PublicationVSP_046153Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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]
    UniGeneiHs.406861.

    Genome annotation databases

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

    Polymorphism databases

    DMDMi1706396.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS4126.1. [P51659-1 ]
    CCDS56378.1. [P51659-3 ]
    CCDS56379.1. [P51659-2 ]
    PIRi S59136.
    RefSeqi NP_000405.1. NM_000414.3. [P51659-1 ]
    NP_001186220.1. NM_001199291.2. [P51659-2 ]
    NP_001186221.1. NM_001199292.1. [P51659-3 ]
    UniGenei Hs.406861.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1IKT X-ray 1.75 A 618-736 [» ]
    1S9C X-ray 3.00 A/B/C/D/E/F/G/H/I/J/K/L 318-615 [» ]
    1ZBQ X-ray 2.71 A/B/C/D/E/F 1-304 [» ]
    ProteinModelPortali P51659.
    SMRi P51659. Positions 3-304, 323-606, 622-736.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109528. 25 interactions.
    IntActi P51659. 16 interactions.
    MINTi MINT-1135639.
    STRINGi 9606.ENSP00000256216.

    Chemistry

    ChEMBLi CHEMBL5814.
    DrugBanki DB00157. NADH.

    PTM databases

    PhosphoSitei P51659.

    Polymorphism databases

    DMDMi 1706396.

    Proteomic databases

    MaxQBi P51659.
    PaxDbi P51659.
    PeptideAtlasi P51659.
    PRIDEi P51659.

    Protocols and materials databases

    DNASUi 3295.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000256216 ; ENSP00000256216 ; ENSG00000133835 . [P51659-1 ]
    ENST00000504811 ; ENSP00000420914 ; ENSG00000133835 . [P51659-2 ]
    ENST00000515320 ; ENSP00000424613 ; ENSG00000133835 . [P51659-3 ]
    GeneIDi 3295.
    KEGGi hsa:3295.
    UCSCi uc003ksj.3. human. [P51659-1 ]

    Organism-specific databases

    CTDi 3295.
    GeneCardsi GC05P118816.
    H-InvDB HIX0078166.
    HGNCi HGNC:5213. HSD17B4.
    HPAi HPA021302.
    HPA021311.
    HPA021479.
    MIMi 233400. phenotype.
    261515. phenotype.
    601860. gene.
    neXtProti NX_P51659.
    Orphaneti 300. Bifunctional enzyme deficiency.
    2855. Perrault syndrome.
    PharmGKBi PA29481.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1028.
    HOGENOMi HOG000170895.
    HOVERGENi HBG002174.
    InParanoidi P51659.
    KOi K12405.
    OMAi CHESCED.
    OrthoDBi EOG7RBZ7V.
    PhylomeDBi P51659.
    TreeFami TF105656.

    Enzyme and pathway databases

    UniPathwayi UPA00659 .
    BioCyci MetaCyc:HS05792-MONOMER.
    Reactomei REACT_11041. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
    REACT_121147. alpha-linolenic acid (ALA) metabolism.
    REACT_17017. Beta-oxidation of pristanoyl-CoA.
    REACT_17062. Beta-oxidation of very long chain fatty acids.
    SABIO-RK P51659.

    Miscellaneous databases

    ChiTaRSi HSD17B4. human.
    EvolutionaryTracei P51659.
    GeneWikii HSD17B4.
    GenomeRNAii 3295.
    NextBioi 13071.
    PROi P51659.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P51659.
    Bgeei P51659.
    CleanExi HS_HSD17B4.
    Genevestigatori P51659.

    Family and domain databases

    Gene3Di 3.10.129.10. 2 hits.
    3.30.1050.10. 1 hit.
    3.40.50.720. 1 hit.
    InterProi IPR002198. DH_sc/Rdtase_SDR.
    IPR002347. Glc/ribitol_DH.
    IPR029069. HotDog_dom.
    IPR002539. MaoC_dom.
    IPR016040. NAD(P)-bd_dom.
    IPR020904. Sc_DH/Rdtase_CS.
    IPR003033. SCP2_sterol-bd_dom.
    [Graphical view ]
    Pfami PF00106. adh_short. 1 hit.
    PF01575. MaoC_dehydratas. 1 hit.
    PF02036. SCP2. 1 hit.
    [Graphical view ]
    PRINTSi PR00081. GDHRDH.
    PR00080. SDRFAMILY.
    SUPFAMi SSF54637. SSF54637. 2 hits.
    SSF55718. SSF55718. 1 hit.
    PROSITEi PS00061. ADH_SHORT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV."
      Adamski J., Normand T., Leenders F., Monte D., Begue A., Stehelin D., Jungblut P.W., de Launoit Y.
      Biochem. J. 311:437-443(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Liver.
    2. "Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein."
      Jiang L.L., Miyazawa S., Souri M., Hashimoto T.
      J. Biochem. 121:364-369(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 69-77; 81-90; 261-270; 291-310; 312-339; 413-426; 451-459; 478-488 AND 590-631, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
    3. "Structure of the gene for the human 17beta-hydroxysteroid dehydrogenase type IV."
      Leenders F., Dolez V., Begue A., Moller G., Gloeckner J.C., de Launoit Y., Adamski J.
      Mamm. Genome 9:1036-1041(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), VARIANTS HIS-106 AND VAL-559.
      Tissue: Lung and Spleen.
    5. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    7. "Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase."
      Jiang L.L., Kobayashi A., Matsuura H., Fukushima H., Hashimoto T.
      J. Biochem. 120:624-632(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    8. "Human peroxisomal multifunctional enzyme type 2. Site-directed mutagenesis studies show the importance of two protic residues for 2-enoyl-CoA hydratase 2 activity."
      Qin Y.M., Haapalainen A.M., Kilpelainen S.H., Marttila M.S., Koski M.K., Glumoff T., Novikov D.K., Hiltunen J.K.
      J. Biol. Chem. 275:4965-4972(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF GLY-16; TYR-347; GLU-366; ASP-370; HIS-406; GLU-408; TYR-410; ASP-490; TYR-505; ASP-510; HIS-515; ASP-517 AND HIS-532.
    9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304 AND SER-309, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    11. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-565; LYS-669 AND LYS-707, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution."
      Haapalainen A.M., van Aalten D.M., Merilaeinen G., Jalonen J.E., Pirilae P., Wierenga R.K., Hiltunen J.K., Glumoff T.
      J. Mol. Biol. 313:1127-1138(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 618-736 IN COMPLEX WITH LIGAND.
    14. "Crystal structure of 2-enoyl-CoA hydratase 2 from human peroxisomal multifunctional enzyme type 2."
      Koski K.M., Haapalainen A.M., Hiltunen J.K., Glumoff T.
      J. Mol. Biol. 345:1157-1169(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 320-614.
    15. "Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency."
      van Grunsven E.G., van Berkel E., Ijlst L., Vreken P., de Klerk J.B.C., Adamski J., Lemonde H., Clayton P.T., Cuebas D.A., Wanders R.J.A.
      Proc. Natl. Acad. Sci. U.S.A. 95:2128-2133(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT DBPD SER-16.
    16. "Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency."
      van Grunsven E.G., Mooijer P.A., Aubourg P., Wanders R.J.
      Hum. Mol. Genet. 8:1509-1516(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT DBPD TYR-457, VARIANT ARG-511.
    17. "D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and contractures of hands and toes."
      Nakano K., Zhang Z., Shimozawa N., Kondo N., Ishii N., Funatsuka M., Shirakawa S., Itoh M., Takashima S., Une M., Kana-aki R.R., Mukai K., Osawa M., Suzuki Y.
      J. Pediatr. 139:865-867(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT DBPD PRO-106.
    18. "Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome."
      Pierce S.B., Walsh T., Chisholm K.M., Lee M.K., Thornton A.M., Fiumara A., Opitz J.M., Levy-Lahad E., Klevit R.E., King M.C.
      Am. J. Hum. Genet. 87:282-288(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PRLTS1 CYS-217.

    Entry informationi

    Entry nameiDHB4_HUMAN
    AccessioniPrimary (citable) accession number: P51659
    Secondary accession number(s): B4DNV1
    , B4DVS5, E9PB82, F5HE57
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 158 of the entry and version 3 of the sequence. [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

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3