P51659 (DHB4_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	736 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. Ref.2 Ref.7
Catalytic activity	(R)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH. Ref.2 (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. Ref.2 (3R)-3-hydroxyacyl-CoA = (2E)-2-enoyl-CoA + H2O. Ref.2
Pathway	Lipid metabolism; fatty acid beta-oxidation.
Subunit structure	Homodimer. Ref.7
Subcellular location	Peroxisome.
Tissue specificity	Present in many tissues with highest concentrations in liver, heart, prostate and testis.
Involvement in disease	D-bifunctional protein deficiency (DBPD) [MIM:261515]: Disorder of peroxisomal fatty acid beta-oxidation. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.16 Ref.17 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18
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.
Biophysicochemical properties	Kinetic parameters: KM=10 µM for D-3-hydroxy-octanoyl-CoA Ref.2 KM=13 µM for NAD KM=2.7 µM for 3-ketooctanoyl-CoA KM=5.4 µM for NADH Vmax=8.8 µmol/min/mg enzyme

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Peroxisome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Disease mutation
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	alpha-linolenic acid metabolic process Traceable author statement. Source: Reactome androgen metabolic process Inferred from direct assay Ref.1. Source: UniProtKB bile acid biosynthetic process Traceable author statement. Source: Reactome estrogen metabolic process Inferred from direct assay Ref.1. Source: UniProtKB fatty acid beta-oxidation using acyl-CoA oxidase Traceable author statement. Source: Reactome medium-chain fatty-acyl-CoA metabolic process Inferred from direct assay Ref.2. Source: UniProtKB very long-chain fatty-acyl-CoA metabolic process Inferred from direct assay Ref.15. Source: UniProtKB
Cellular_component	peroxisomal matrix Traceable author statement. Source: Reactome peroxisomal membrane Inferred from direct assay PubMed 21525035. Source: UniProtKB
Molecular_function	17-beta-hydroxysteroid dehydrogenase (NAD+) activity Inferred from direct assay Ref.1. Source: UniProtKB 3-hydroxyacyl-CoA dehydrogenase activity Inferred from direct assay Ref.2. Source: UniProtKB 3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity Traceable author statement. Source: Reactome isomerase activity Inferred from electronic annotation. Source: UniProtKB-KW long-chain-enoyl-CoA hydratase activity Inferred from direct assay Ref.16Ref.2Ref.15. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.14Ref.2. Source: UniProtKB sterol binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P51659-1)

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.

Isoform 2 (identifier: P51659-2)

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

Note: No experimental confirmation available.

Isoform 3 (identifier: P51659-3)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 736

735

Peroxisomal multifunctional enzyme type 2

PRO_0000054583

Chain

2 – 311

310

(3R)-hydroxyacyl-CoA dehydrogenase

PRO_0000400082

Chain

312 – 736

425

Enoyl-CoA hydratase 2

PRO_0000400083

Regions

Domain

484 – 600

117

MaoC-like

Domain

624 – 736

113

SCP2

Nucleotide binding

13 – 37

25

NAD By similarity

Nucleotide binding

75 – 76

2

NAD

Nucleotide binding

164 – 168

5

NAD

Nucleotide binding

196 – 199

4

NAD

Region

2 – 305

304

(3R)-hydroxyacyl-CoA dehydrogenase

Region

322 – 622

301

Enoyl-CoA hydratase 2

Region

406 – 407

2

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

Region

510 – 515

6

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

Motif

734 – 736

3

Microbody targeting signal Potential

Sites

Active site

164

1

Proton acceptor By similarity

Binding site

21

1

NAD; via amide nitrogen

Binding site

40

1

NAD

Binding site

99

1

NAD; via carbonyl oxygen

Binding site

151

1

Substrate By similarity

Binding site

435

1

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

Binding site

533

1

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

Binding site

563

1

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

Binding site

706

1

Substrate

Binding site

724

1

Substrate

Amino acid modifications

Modified residue

3

1

Phosphoserine By similarity

Modified residue

304

1

Phosphoserine Ref.9

Modified residue

309

1

Phosphoserine Ref.9

Modified residue

565

1

N6-acetyllysine Ref.11

Modified residue

663

1

N6-acetyllysine By similarity

Modified residue

669

1

N6-acetyllysine Ref.11

Modified residue

707

1

N6-acetyllysine Ref.11

Natural variations

Alternative sequence

1 – 38

38

MGSPL…ALVVV → MVILEAPHLLRRKEPETPGL SSRIGPSLCPGFCRKRSVSC CFQNLCNNPMEKIISQCRFF VSM in isoform 2.

VSP_046152

Alternative sequence

20 – 37

18

Missing in isoform 3.

VSP_046153

Natural variant

16

1

G → S in DBPD. Ref.15

VAR_037576

Natural variant

90

1

F → L.
Corresponds to variant rs28943588 [ dbSNP | Ensembl ].

VAR_052309

Natural variant

106

1

R → H. Ref.4
Corresponds to variant rs25640 [ dbSNP | Ensembl ].

VAR_014872

Natural variant

106

1

R → P in DBPD. Ref.17

VAR_065906

Natural variant

140

1

K → N.
Corresponds to variant rs28943589 [ dbSNP | Ensembl ].

VAR_052310

Natural variant

217

1

Y → C in PRLTS1. Ref.18

VAR_065907

Natural variant

292

1

T → S.
Corresponds to variant rs1143650 [ dbSNP | Ensembl ].

VAR_024625

Natural variant

427

1

A → V.
Corresponds to variant rs28943590 [ dbSNP | Ensembl ].

VAR_052311

Natural variant

457

1

N → Y in DBPD; the mutation leads to an unstable protein. Ref.16

VAR_065908

Natural variant

491

1

A → T.
Corresponds to variant rs28943591 [ dbSNP | Ensembl ].

VAR_052312

Natural variant

511

1

W → R. Ref.16
Corresponds to variant rs11539471 [ dbSNP | Ensembl ].

VAR_014873

Natural variant

559

1

I → V. Ref.4
Corresponds to variant rs11205 [ dbSNP | Ensembl ].

VAR_014874

Natural variant

606

1

A → S.
Corresponds to variant rs15228 [ dbSNP | Ensembl ].

VAR_052313

Natural variant

687

1

T → I.
Corresponds to variant rs28943592 [ dbSNP | Ensembl ].

VAR_052314

Natural variant

728

1

M → V.
Corresponds to variant rs28943594 [ dbSNP | Ensembl ].

VAR_052315

Experimental info

Mutagenesis

16

1

G → S: No dehydrogenase activity. Ref.8

Mutagenesis

347

1

Y → A: No hydratase activity. Ref.8

Mutagenesis

366

1

E → A: No hydratase activity. Ref.8

Mutagenesis

370

1

D → A: No effect. Ref.8

Mutagenesis

406

1

H → A: No effect. Ref.8

Mutagenesis

408

1

E → A: No effect. Ref.8

Mutagenesis

410

1

Y → A: No effect. Ref.8

Mutagenesis

490

1

D → A: No effect. Ref.8

Mutagenesis

505

1

Y → A: Completely inactive. Ref.8

Mutagenesis

510

1

D → A: No hydratase activity. Ref.8

Mutagenesis

515

1

H → A: Completely inactive. Ref.8

Mutagenesis

517

1

D → A: No effect. Ref.8

Mutagenesis

532

1

H → A: No effect. Ref.8

Sequence conflict

587

1

Q → R in BAG60363. Ref.4

Secondary structure

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736

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 – 90

12

Beta strand

95 – 98

4

Helix

108 – 110

3

Helix

113 – 141

29

Beta strand

144 – 149

6

Helix

152 – 156

5

Helix

162 – 182

21

Helix

183 – 185

3

Beta strand

187 – 194

8

Turn

199 – 204

6

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 – 277

5

Helix

288 – 303

16

Beta strand

335 – 339

5

Helix

341 – 350

10

Helix

358 – 360

3

Helix

361 – 364

4

Helix

375 – 377

3

Helix

378 – 381

4

Helix

383 – 385

3

Beta strand

405 – 415

11

Beta strand

419 – 432

14

Beta strand

440 – 462

23

Beta strand

490 – 496

7

Helix

501 – 505

5

Helix

506 – 508

3

Helix

513 – 515

3

Helix

518 – 522

5

Turn

523 – 525

3

Helix

533 – 548

16

Helix

553 – 555

3

Beta strand

556 – 563

8

Beta strand

572 – 580

9

Beta strand

583 – 590

8

Turn

591 – 593

3

Beta strand

596 – 605

10

Helix

624 – 646

23

Beta strand

648 – 670

23

Beta strand

674 – 679

6

Beta strand

685 – 691

7

Helix

692 – 699

8

Helix

705 – 710

6

Beta strand

713 – 719

7

Helix

720 – 733

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 7B11E02483328BCE	FASTA	736	79,686
	10 20 30 40 50 60 MGSPLRFDGR VVLVTGAGAG LGRAYALAFA ERGALVVVND LGGDFKGVGK GSLAADKVVE 70 80 90 100 110 120 EIRRRGGKAV ANYDSVEEGE KVVKTALDAF GRIDVVVNNA GILRDRSFAR ISDEDWDIIH 130 140 150 160 170 180 RVHLRGSFQV TRAAWEHMKK QKYGRIIMTS SASGIYGNFG QANYSAAKLG LLGLANSLAI 190 200 210 220 230 240 EGRKSNIHCN TIAPNAGSRM TQTVMPEDLV EALKPEYVAP LVLWLCHESC EENGGLFEVG 250 260 270 280 290 300 AGWIGKLRWE RTLGAIVRQK NHPMTPEAVK ANWKKICDFE NASKPQSIQE STGSIIEVLS 310 320 330 340 350 360 KIDSEGGVSA NHTSRATSTA TSGFAGAIGQ KLPPFSYAYT ELEAIMYALG VGASIKDPKD 370 380 390 400 410 420 LKFIYEGSSD FSCLPTFGVI IGQKSMMGGG LAEIPGLSIN FAKVLHGEQY LELYKPLPRA 430 440 450 460 470 480 GKLKCEAVVA DVLDKGSGVV IIMDVYSYSE KELICHNQFS LFLVGSGGFG GKRTSDKVKV 490 500 510 520 530 540 AVAIPNRPPD AVLTDTTSLN QAALYRLSGD WNPLHIDPNF ASLAGFDKPI LHGLCTFGFS 550 560 570 580 590 600 ARRVLQQFAD NDVSRFKAIK ARFAKPVYPG QTLQTEMWKE GNRIHFQTKV QETGDIVISN 610 620 630 640 650 660 AYVDLAPTSG TSAKTPSEGG KLQSTFVFEE IGRRLKDIGP EVVKKVNAVF EWHITKGGNI 670 680 690 700 710 720 GAKWTIDLKS GSGKVYQGPA KGAADTTIIL SDEDFMEVVL GKLDPQKAFF SGRLKARGNI 730 MLSQKLQMIL KDYAKL
	Isoform 2 [UniParc]. Checksum: 246D60646BD2C7A8	FASTA	761	83,025
	10 20 30 40 50 60 MVILEAPHLL RRKEPETPGL SSRIGPSLCP GFCRKRSVSC CFQNLCNNPM EKIISQCRFF 70 80 90 100 110 120 VSMNDLGGDF KGVGKGSLAA DKVVEEIRRR GGKAVANYDS VEEGEKVVKT ALDAFGRIDV 130 140 150 160 170 180 VVNNAGILRD RSFARISDED WDIIHRVHLR GSFQVTRAAW EHMKKQKYGR IIMTSSASGI 190 200 210 220 230 240 YGNFGQANYS AAKLGLLGLA NSLAIEGRKS NIHCNTIAPN AGSRMTQTVM PEDLVEALKP 250 260 270 280 290 300 EYVAPLVLWL CHESCEENGG LFEVGAGWIG KLRWERTLGA IVRQKNHPMT PEAVKANWKK 310 320 330 340 350 360 ICDFENASKP QSIQESTGSI IEVLSKIDSE GGVSANHTSR ATSTATSGFA GAIGQKLPPF 370 380 390 400 410 420 SYAYTELEAI MYALGVGASI KDPKDLKFIY EGSSDFSCLP TFGVIIGQKS MMGGGLAEIP 430 440 450 460 470 480 GLSINFAKVL HGEQYLELYK PLPRAGKLKC EAVVADVLDK GSGVVIIMDV YSYSEKELIC 490 500 510 520 530 540 HNQFSLFLVG SGGFGGKRTS DKVKVAVAIP NRPPDAVLTD TTSLNQAALY RLSGDWNPLH 550 560 570 580 590 600 IDPNFASLAG FDKPILHGLC TFGFSARRVL QQFADNDVSR FKAIKARFAK PVYPGQTLQT 610 620 630 640 650 660 EMWKEGNRIH FQTKVQETGD IVISNAYVDL APTSGTSAKT PSEGGKLQST FVFEEIGRRL 670 680 690 700 710 720 KDIGPEVVKK VNAVFEWHIT KGGNIGAKWT IDLKSGSGKV YQGPAKGAAD TTIILSDEDF 730 740 750 760 MEVVLGKLDP QKAFFSGRLK ARGNIMLSQK LQMILKDYAK L
	Isoform 3 [UniParc]. Checksum: 79C506BC0D73B5C2	FASTA	718	77,870
	10 20 30 40 50 60 MGSPLRFDGR VVLVTGAGAV NDLGGDFKGV GKGSLAADKV VEEIRRRGGK AVANYDSVEE 70 80 90 100 110 120 GEKVVKTALD AFGRIDVVVN NAGILRDRSF ARISDEDWDI IHRVHLRGSF QVTRAAWEHM 130 140 150 160 170 180 KKQKYGRIIM TSSASGIYGN FGQANYSAAK LGLLGLANSL AIEGRKSNIH CNTIAPNAGS 190 200 210 220 230 240 RMTQTVMPED LVEALKPEYV APLVLWLCHE SCEENGGLFE VGAGWIGKLR WERTLGAIVR 250 260 270 280 290 300 QKNHPMTPEA VKANWKKICD FENASKPQSI QESTGSIIEV LSKIDSEGGV SANHTSRATS 310 320 330 340 350 360 TATSGFAGAI GQKLPPFSYA YTELEAIMYA LGVGASIKDP KDLKFIYEGS SDFSCLPTFG 370 380 390 400 410 420 VIIGQKSMMG GGLAEIPGLS INFAKVLHGE QYLELYKPLP RAGKLKCEAV VADVLDKGSG 430 440 450 460 470 480 VVIIMDVYSY SEKELICHNQ FSLFLVGSGG FGGKRTSDKV KVAVAIPNRP PDAVLTDTTS 490 500 510 520 530 540 LNQAALYRLS GDWNPLHIDP NFASLAGFDK PILHGLCTFG FSARRVLQQF ADNDVSRFKA 550 560 570 580 590 600 IKARFAKPVY PGQTLQTEMW KEGNRIHFQT KVQETGDIVI SNAYVDLAPT SGTSAKTPSE 610 620 630 640 650 660 GGKLQSTFVF EEIGRRLKDI GPEVVKKVNA VFEWHITKGG NIGAKWTIDL KSGSGKVYQG 670 680 690 700 710 PAKGAADTTI ILSDEDFMEV VLGKLDPQKA FFSGRLKARG NIMLSQKLQM ILKDYAKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304 AND SER-309, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] 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.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00019912.
IPI00909582.
IPI00965117.

PIR

S59136.

RefSeq

NP_000405.1. NM_000414.3.
NP_001186220.1. NM_001199291.1.
NP_001186221.1. NM_001199292.1.

UniGene

Hs.406861.

3D structure databases

PDBe
RCSB PDB
PDBj

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	320-614	[»]
1ZBQ	X-ray	2.71	A/B/C/D/E/F	1-304	[»]

ProteinModelPortal

P51659.

ModBase

Search...

Protein-protein interaction databases

IntAct

P51659. 14 interactions.

MINT

MINT-1135639.

STRING

9606.ENSP00000256216.

PTM databases

PhosphoSite

P51659.

Polymorphism databases

DMDM

1706396.

Proteomic databases

PaxDb

P51659.

PeptideAtlas

P51659.

PRIDE

P51659.

Protocols and materials databases

DNASU

3295.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256216; ENSP00000256216; ENSG00000133835.
ENST00000504811; ENSP00000420914; ENSG00000133835.
ENST00000515320; ENSP00000424613; ENSG00000133835.

GeneID

3295.

KEGG

hsa:3295.

UCSC

uc003ksj.3. human.
uc011cwh.2. human.
uc011cwi.2. human.

Organism-specific databases

CTD

3295.

GeneCards

GC05P118816.

H-InvDB

HIX0078166.

HGNC

HGNC:5213. HSD17B4.

HPA

HPA021302.
HPA021311.
HPA021479.

MIM

233400. phenotype.
261515. phenotype.
601860. gene.

neXtProt

NX_P51659.

Orphanet

300. Bifunctional enzyme deficiency.
2855. Perrault syndrome.

PharmGKB

PA29481.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1028.

HOGENOM

HOG000170895.

HOVERGEN

HBG002174.

InParanoid

P51659.

KO

K12405.

OrthoDB

EOG4255S8.

PhylomeDB

P51659.

Enzyme and pathway databases

BioCyc

MetaCyc:HS05792-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P51659.

UniPathway

UPA00659.

Gene expression databases

ArrayExpress

P51659.

Bgee

P51659.

CleanEx

HS_HSD17B4.

Genevestigator

P51659.

GermOnline

ENSG00000133835. Homo sapiens.

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.
IPR020904. Sc_DH/Rdtase_CS.
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. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5814.

ChiTaRS

HSD17B4. human.

DrugBank

DB00157. NADH.

EvolutionaryTrace

P51659.

GenomeRNAi

3295.

NextBio

13071.

SOURCE

Search...

Entry information

Entry name

DHB4_HUMAN

Accession

Primary (citable) accession number: P51659
Secondary accession number(s): B4DNV1 , B4DVS5, E9PB82, F5HE57

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 143 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.