P97852 (DHB4_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

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

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	735 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Fatty acid metabolism Lipid metabolism
Cellular component	Peroxisome
Ligand	NAD
Molecular function	Isomerase Lyase Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Sertoli cell development Inferred from electronic annotation. Source: Compara cholesterol metabolic process Non-traceable author statement Ref.3. Source: RGD fatty acid beta-oxidation Inferred from electronic annotation. Source: UniProtKB-UniPathway very long-chain fatty acid metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrion Inferred from electronic annotation. Source: Compara peroxisome Inferred from direct assay PubMed 14561759. Source: HGNC
Molecular_function	3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity Inferred from electronic annotation. Source: EC isomerase activity Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 735

734

Peroxisomal multifunctional enzyme type 2

PRO_0000054585

Chain

2 – 311

310

(3R)-hydroxyacyl-CoA dehydrogenase

PRO_0000400086

Chain

312 – 735

424

Enoyl-CoA hydratase 2

PRO_0000400087

Regions

Domain

483 – 599

117

MaoC-like

Domain

623 – 735

113

SCP2

Nucleotide binding

16 – 40

25

NAD

Nucleotide binding

75 – 76

2

NAD By similarity

Nucleotide binding

164 – 168

5

NAD By similarity

Nucleotide binding

196 – 199

4

NAD By similarity

Region

2 – 305

304

(3R)-hydroxyacyl-CoA dehydrogenase

Region

321 – 621

301

Enoyl-CoA hydratase 2

Region

405 – 406

2

(3R)-3-hydroxydecanoyl-CoA binding By similarity

Region

509 – 514

6

(3R)-3-hydroxydecanoyl-CoA binding By similarity

Motif

733 – 735

3

Microbody targeting signal Potential

Sites

Active site

164

1

Proton acceptor

Binding site

21

1

NAD; via amide nitrogen By similarity

Binding site

40

1

NAD By similarity

Binding site

99

1

NAD; via carbonyl oxygen By similarity

Binding site

151

1

Substrate

Binding site

434

1

(3R)-3-hydroxydecanoyl-CoA By similarity

Binding site

532

1

(3R)-3-hydroxydecanoyl-CoA; via amide nitrogen By similarity

Binding site

562

1

(3R)-3-hydroxydecanoyl-CoA; via carbonyl oxygen By similarity

Binding site

705

1

Substrate By similarity

Binding site

723

1

Substrate By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

3

1

Phosphoserine By similarity

Modified residue

304

1

Phosphoserine By similarity

Modified residue

308

1

Phosphoserine By similarity

Modified residue

564

1

N6-acetyllysine By similarity

Modified residue

662

1

N6-acetyllysine By similarity

Modified residue

668

1

N6-acetyllysine By similarity

Experimental info

Sequence conflict

1 – 2

2

MA → M in CAA64427. Ref.1

Sequence conflict

12

1

V → G in CAA64427. Ref.1

Sequence conflict

26

1

A → G in CAA64427. Ref.1

Sequence conflict

76

1

V → G in AAB09724. Ref.4

Sequence conflict

106

1

R → P in CAA64427. Ref.1

Sequence conflict

157

1

G → S in AAB09724. Ref.4

Sequence conflict

284

1

K → E in CAA64427. Ref.1

Sequence conflict

368

1

A → P in CAA64427. Ref.1

Sequence conflict

376

1

F → I in CAA64427. Ref.1

Sequence conflict

386

1

M → T in AAB09724. Ref.4

Sequence conflict

485

1

S → D in AAB09724. Ref.4

Sequence conflict

498

1

L → V in CAA64427. Ref.1

Sequence conflict

521

1

S → G in CAA64427. Ref.1

Secondary structure

1

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735

Helix Strand Turn

Details...

Beta strand

11 – 14

4

Turn

15 – 18

4

Helix

20 – 31

12

Beta strand

35 – 39

5

Helix

53 – 64

12

Beta strand

68 – 72

5

Helix

76 – 78

3

Helix

79 – 89

11

Beta strand

95 – 98

4

Helix

108 – 110

3

Helix

113 – 141

29

Beta strand

144 – 149

6

Helix

152 – 156

5

Helix

162 – 181

20

Helix

183 – 185

3

Beta strand

187 – 195

9

Turn

199 – 201

3

Helix

202 – 204

3

Helix

207 – 212

6

Helix

215 – 217

3

Helix

219 – 225

7

Beta strand

236 – 240

5

Beta strand

243 – 251

9

Helix

266 – 271

6

Helix

273 – 276

4

Helix

288 – 302

15

Sequences

	Sequence		Length	Mass (Da)
	P97852 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: E14F15FFD35FC7D8	FASTA	735	79,428
	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

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.

IPI

IPI00561647.

RefSeq

NP_077368.2. NM_024392.2.

UniGene

Rn.2082.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GZ6	X-ray	2.38	A/B/C/D	1-319	[»]

ProteinModelPortal

P97852.

SMR

P97852. Positions 3-303, 322-604, 621-735.

ModBase

Search...

Protein-protein interaction databases

IntAct

P97852. 1 interaction.

STRING

10116.ENSRNOP00000043755.

PTM databases

PhosphoSite

P97852.

Proteomic databases

PaxDb

P97852.

PRIDE

P97852.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000021646; ENSRNOP00000021646; ENSRNOG00000015840.

GeneID

79244.

KEGG

rno:79244.

UCSC

RGD:621806. rat.

Organism-specific databases

CTD

3295.

RGD

621806. Hsd17b4.

Phylogenomic databases

eggNOG

COG1028.

GeneTree

ENSGT00530000062928.

HOGENOM

HOG000170895.

HOVERGEN

HBG002174.

KO

K12405.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-14329.

UniPathway

UPA00659.

Gene expression databases

ArrayExpress

P97852.

Genevestigator

P97852.

GermOnline

ENSRNOG00000015840. Rattus norvegicus.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR002539. MaoC_dom.
IPR016040. NAD(P)-bd_dom.
IPR003033. SCP2_sterol-bd_dom.
[Graphical view]

Pfam

PF00106. adh_short. 1 hit.
PF01575. MaoC_dehydratas. 1 hit.
PF02036. SCP2. 1 hit.
[Graphical view]

PRINTS

PR00081. GDHRDH.
PR00080. SDRFAMILY.

SUPFAM

SSF55718. SCP2. 1 hit.

PROSITE

PS00061. ADH_SHORT. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1075219.

EvolutionaryTrace

P97852.

NextBio

614694.

Entry information

Entry name

DHB4_RAT

Accession

Primary (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:	April 3, 2013
This is version 108 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program