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P97852 (DHB4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. (3R)-hydroxyacyl-CoA dehydrogenase
    EC=1.1.1.n12
  2. Enoyl-CoA hydratase 2
    EC=4.2.1.107
    EC=4.2.1.119
    Alternative name(s):
    3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase
Gene names
Name:Hsd17b4
Synonyms:Edh17b4
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length735 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

(R)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH.

(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.

(3R)-3-hydroxyacyl-CoA = (2E)-2-enoyl-CoA + H2O.

Pathway

Lipid metabolism; fatty acid beta-oxidation.

Subunit structure

Homodimer. Ref.6

Subcellular location

Peroxisome Ref.1.

Miscellaneous

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

Sequence similarities

Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Contains 1 MaoC-like domain.

Contains 1 SCP2 domain.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
   Cellular componentPeroxisome
   LigandNAD
   Molecular functionIsomerase
Lyase
Oxidoreductase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processSertoli cell development

Inferred from electronic annotation. Source: Ensembl

androgen metabolic process

Inferred from electronic annotation. Source: Ensembl

cholesterol metabolic process

Non-traceable author statement Ref.3. Source: RGD

estrogen metabolic process

Inferred from electronic annotation. Source: Ensembl

fatty acid beta-oxidation

Inferred from electronic annotation. Source: UniProtKB-UniPathway

medium-chain fatty-acyl-CoA metabolic process

Inferred from electronic annotation. Source: Ensembl

very long-chain fatty acid metabolic process

Inferred from electronic annotation. Source: Ensembl

very long-chain fatty-acyl-CoA metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentmitochondrion

Inferred from electronic annotation. Source: Ensembl

peroxisomal membrane

Inferred from electronic annotation. Source: Ensembl

peroxisome

Inferred from direct assay PubMed 14561759. Source: HGNC

   Molecular_function17-beta-hydroxysteroid dehydrogenase (NAD+) activity

Inferred from electronic annotation. Source: Ensembl

3-hydroxyacyl-CoA dehydrogenase activity

Inferred from electronic annotation. Source: Ensembl

3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity

Inferred from electronic annotation. Source: UniProtKB-EC

isomerase activity

Inferred from electronic annotation. Source: UniProtKB-KW

long-chain-enoyl-CoA hydratase activity

Inferred from electronic annotation. Source: Ensembl

sterol binding

Inferred from electronic annotation. Source: InterPro

testosterone dehydrogenase [NAD(P)] activity

Traceable author statement Ref.3. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 735735Peroxisomal multifunctional enzyme type 2
PRO_0000054585
Chain1 – 311311(3R)-hydroxyacyl-CoA dehydrogenase
PRO_0000400086
Chain312 – 735424Enoyl-CoA hydratase 2
PRO_0000400087

Regions

Domain483 – 599117MaoC-like
Domain623 – 735113SCP2
Nucleotide binding16 – 4025NAD
Nucleotide binding75 – 762NAD By similarity
Nucleotide binding164 – 1685NAD By similarity
Nucleotide binding196 – 1994NAD By similarity
Region1 – 305305(3R)-hydroxyacyl-CoA dehydrogenase
Region321 – 621301Enoyl-CoA hydratase 2
Region405 – 4062(3R)-3-hydroxydecanoyl-CoA binding By similarity
Region509 – 5146(3R)-3-hydroxydecanoyl-CoA binding By similarity
Motif733 – 7353Microbody targeting signal Potential

Sites

Active site1641Proton acceptor
Binding site211NAD; via amide nitrogen By similarity
Binding site401NAD By similarity
Binding site991NAD; via carbonyl oxygen By similarity
Binding site1511Substrate
Binding site4341(3R)-3-hydroxydecanoyl-CoA By similarity
Binding site5321(3R)-3-hydroxydecanoyl-CoA; via amide nitrogen By similarity
Binding site5621(3R)-3-hydroxydecanoyl-CoA; via carbonyl oxygen By similarity
Binding site7051Substrate By similarity
Binding site7231Substrate By similarity

Amino acid modifications

Modified residue461N6-acetyllysine; alternate By similarity
Modified residue461N6-succinyllysine; alternate By similarity
Modified residue571N6-succinyllysine By similarity
Modified residue681N6-succinyllysine By similarity
Modified residue841N6-succinyllysine By similarity
Modified residue2751N6-succinyllysine By similarity
Modified residue3041Phosphoserine By similarity
Modified residue3081Phosphoserine By similarity
Modified residue3551N6-succinyllysine By similarity
Modified residue4231N6-succinyllysine By similarity
Modified residue5641N6-acetyllysine By similarity
Modified residue5781N6-succinyllysine By similarity
Modified residue6621N6-succinyllysine By similarity
Modified residue6681N6-acetyllysine By similarity
Modified residue7241N6-succinyllysine By similarity

Experimental info

Sequence conflict1 – 22MA → M in CAA64427. Ref.1
Sequence conflict121V → G in CAA64427. Ref.1
Sequence conflict261A → G in CAA64427. Ref.1
Sequence conflict761V → G in AAB09724. Ref.4
Sequence conflict1061R → P in CAA64427. Ref.1
Sequence conflict1571G → S in AAB09724. Ref.4
Sequence conflict2841K → E in CAA64427. Ref.1
Sequence conflict3681A → P in CAA64427. Ref.1
Sequence conflict3761F → I in CAA64427. Ref.1
Sequence conflict3861M → T in AAB09724. Ref.4
Sequence conflict4851S → D in AAB09724. Ref.4
Sequence conflict4981L → V in CAA64427. Ref.1
Sequence conflict5211S → G in CAA64427. Ref.1

Secondary structure

.................................................. 735
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P97852 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E14F15FFD35FC7D8

FASTA73579,428
        10         20         30         40         50         60 
MASPLRFDGR VVLVTGAGGG LGRAYALAFA ERGALVVVND LGGDFKGVGK GSSAADKVVE 

        70         80         90        100        110        120 
EIRRRGGKAV ANYDSVEAGE KLVKTALDTF GRIDVVVNNA GILRDRSFSR ISDEDWDIIQ 

       130        140        150        160        170        180 
RVHLRGSFQV TRAAWDHMKK QNYGRIIMTA SASGIYGNFG QANYSAAKLG LLGLANTLVI 

       190        200        210        220        230        240 
EGRKNNIHCN TIAPNAGSRM TETVMPEDLV EALKPEYVAP LVLWLCHESC EENGGLFEVG 

       250        260        270        280        290        300 
AGWIGKLRWE RTLGAIVRKR NQPMTPEAVR DNWVKICDFS NASKPKSIQE STGGIIEVLH 

       310        320        330        340        350        360 
KIDSEGISQN HTGQVASADA SGFAGVVGHK LPSFSSSYTE LQCIMYALGV GASVKNPKDL 

       370        380        390        400        410        420 
KFVYEGSADF SCLPTFGVIV AQKSLMSGGL AEVPGLSINF AKVLHGEQYL ELYKPLPRSG 

       430        440        450        460        470        480 
ELKCEAVIAD ILDKGSGIVI VMDVYSYSGK ELICYNQFSV FVVGSGGFGG KRTSEKLKAA 

       490        500        510        520        530        540 
VAVPSRPPDA VLRDTTSLNQ AALYRLSGDS NPLHIDPSFA SIAGFEKPIL HGLCTFGFSA 

       550        560        570        580        590        600 
RHVLQQFADN DVSRFKAIKV RFAKPVYPGQ TLQTEMWKEG NRIHFQTKVQ ETGDIVISNA 

       610        620        630        640        650        660 
YVDLVPTSGV SAQTPSEGGA LQSALVFGEI GRRLKDVGRE VVKKVNAVFE WHITKNGNVA 

       670        680        690        700        710        720 
AKWTIDLKNG SGEVYQGPAK GSADTTITIS DEDFMEVVLG KLNPQNAFFS GRLKARGNIM 

       730 
LSQKLQMILK DYAKL 

« Hide

References

[1]"Further characterization of the peroxisomal 3-hydroxyacyl-CoA dehydrogenases from rat liver. Relationship between the different dehydrogenases and evidence that fatty acids and the C27 bile acids di- and tri-hydroxycoprostanic acids are metabolized by separate multifunctional proteins."
Dieuaide-Noubhani M., Novikov D., Baumgart E., Vanhooren J.C.T., Fransen M., Goethals M., Vandekerckhove J., Van Veldhoven P.P., Mannaerts G.P.
Eur. J. Biochem. 240:660-666(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 26-30; 32-44; 110-115; 132-139 AND 270-274, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE.
Tissue: Liver.
[2]Erratum
Dieuaide-Noubhani M., Novikov D., Baumgart E., Vanhooren J.C.T., Fransen M., Goethals M., Vandekerckhove J., Van Veldhoven P.P., Mannaerts G.P.
Eur. J. Biochem. 243:537-537(1997)
[3]"Rat 17 beta-hydroxysteroid dehydrogenase type IV is a novel peroxisome proliferator-inducible gene."
Corton J.C., Bocos C., Moreno E.S., Merritt A., Marsman D.S., Sausen P.J., Cattley R.C., Gustafsson J.-A.
Mol. Pharmacol. 50:1157-1166(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[4]"Peroxisomal multifunctional enzyme of beta-oxidation metabolizing D-3-hydroxyacyl-CoA esters in rat liver: molecular cloning, expression and characterization."
Qin Y.M., Poutanen M.H., Helander H.M., Kvist A.P., Siivari K.M., Schmitz W., Conzelmann E., Hellman U., Hiltunen J.K.
Biochem. J. 321:21-28(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 318-330; 479-505; 542-554; 562-576 AND 583-587, ENZYME CATALYSIS.
[5]"Identification and characterization of the 2-enoyl-CoA hydratases involved in peroxisomal beta-oxidation in rat liver."
Dieuaide-Noubhani M., Novikov D., Vandekerckhove J., Veldhoven P.P., Mannaerts G.P.
Biochem. J. 321:253-259(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 312-324, PROTEOLYTIC CLEAVAGE.
[6]"Binary structure of the two-domain (3R)-hydroxyacyl-CoA dehydrogenase from rat peroxisomal multifunctional enzyme type 2 at 2.38 A resolution."
Haapalainen A.M., Koski M.K., Qin Y.-M., Hiltunen J.K., Glumoff T.
Structure 11:87-97(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 1-319 IN COMPLEX WITH NAD, HOMODIMERIZATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S83279 mRNA. Translation: AAB49519.1.
U37486 mRNA. Translation: AAB09724.1.
X94978 mRNA. Translation: CAA64427.1.
RefSeqNP_077368.2. NM_024392.2.
UniGeneRn.2082.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GZ6X-ray2.38A/B/C/D1-319[»]
ProteinModelPortalP97852.
SMRP97852. Positions 3-303, 322-604, 621-735.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP97852. 1 interaction.
STRING10116.ENSRNOP00000043755.

Chemistry

ChEMBLCHEMBL1075219.

PTM databases

PhosphoSiteP97852.

Proteomic databases

PaxDbP97852.
PRIDEP97852.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000021646; ENSRNOP00000021646; ENSRNOG00000015840.
GeneID79244.
KEGGrno:79244.
UCSCRGD:621806. rat.

Organism-specific databases

CTD3295.
RGD621806. Hsd17b4.

Phylogenomic databases

eggNOGCOG1028.
GeneTreeENSGT00530000062928.
HOGENOMHOG000170895.
HOVERGENHBG002174.
KOK12405.
OMATETIMPP.
OrthoDBEOG7RBZ7V.

Enzyme and pathway databases

BioCycMetaCyc:MONOMER-14329.
UniPathwayUPA00659.

Gene expression databases

GenevestigatorP97852.

Family and domain databases

Gene3D3.10.129.10. 2 hits.
3.30.1050.10. 1 hit.
3.40.50.720. 1 hit.
InterProIPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR029069. HotDog_dom.
IPR002539. MaoC_dom.
IPR016040. NAD(P)-bd_dom.
IPR003033. SCP2_sterol-bd_dom.
[Graphical view]
PfamPF00106. adh_short. 1 hit.
PF01575. MaoC_dehydratas. 1 hit.
PF02036. SCP2. 1 hit.
[Graphical view]
PRINTSPR00081. GDHRDH.
PR00080. SDRFAMILY.
SUPFAMSSF54637. SSF54637. 2 hits.
SSF55718. SSF55718. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP97852.
NextBio614694.
PROP97852.

Entry information

Entry nameDHB4_RAT
AccessionPrimary (citable) accession number: P97852
Secondary accession number(s): P70523, P70540
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: June 11, 2014
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways