Reviewed, UniProtKB/Swiss-Prot Q9BUT1 (BDH2_HUMAN)

Names and origin

Protein names

Recommended name:
    3-hydroxybutyrate dehydrogenase type 2
    EC=1.1.1.30
Alternative name(s):
    R-beta-hydroxybutyrate dehydrogenase
    Dehydrogenase/reductase SDR family member 6
    Oxidoreductase UCPA

Gene names

Name:	BDH2
Synonyms:	DHRS6
ORF Names:	UNQ6308/PRO20933

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	245 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	(R)-3-hydroxybutanoate + NAD+ = acetoacetate + NADH.
Subunit structure	Homotetramer. Ref.9
Subcellular location	Cytoplasm. Ref.9
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Biophysicochemical properties	Kinetic parameters: KM=60 µM for NAD KM=10 mM for R-hydroxybutyrate Vmax=82 nmol/min/mg enzyme (at 30 degrees Celsius) pH dependence: Optimum pH is 7.5-9.0.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	fatty acid beta-oxidation Ref.9 Inferred from direct assay. Source: HGNC oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.9 Inferred from direct assay. Source: HGNC
Molecular function	3-hydroxybutyrate dehydrogenase activity Ref.9 Inferred from direct assay. Source: HGNC NAD or NADH binding Ref.9 Inferred from direct assay. Source: HGNC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BUT1-1)

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: Q9BUT1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     141-245: VVNRCVYSTT...PVIIDGGWSL → GSVSFRGLRCSYTHIIKSSAFGNRHSRDYNFKY

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 245

245

3-hydroxybutyrate dehydrogenase type 2

PRO_0000042580

Regions

Nucleotide binding

10 – 37

28

NAD

Nucleotide binding

180 – 184

5

NAD

Sites

Active site

147

1

Proton acceptor By similarity

Binding site

58

1

NAD

Binding site

144

1

Substrate Probable

Binding site

151

1

NAD

Binding site

188

1

Substrate Probable

Binding site

205

1

Substrate Probable

Amino acid modifications

Modified residue

48

1

N6-acetyllysine Ref.8

Modified residue

132

1

Phosphoserine Ref.6

Natural variations

Alternative sequence

141 – 245

105

VVNRC…GGWSL → GSVSFRGLRCSYTHIIKSSA FGNRHSRDYNFKY in isoform 2.

VSP_015859

Natural variant

70

1

N → S: dbSNP rs1054707. Ref.2 Ref.3 Ref.5

VAR_023602

Experimental info

Sequence conflict

161

1

V → L in AAQ89200. Ref.2

Sequence conflict

230

1

A → T in AAH95414. Ref.5

Secondary structure

1

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245

Helix Strand Turn

Details...

Turn

3 – 6

4

Beta strand

8 – 13

6

Helix

17 – 28

12

Beta strand

32 – 38

7

Helix

40 – 43

4

Helix

44 – 48

5

Beta strand

52 – 56

5

Helix

62 – 71

10

Beta strand

76 – 80

5

Helix

90 – 92

3

Helix

95 – 105

11

Helix

107 – 123

17

Beta strand

126 – 131

6

Turn

136 – 138

3

Helix

145 – 165

21

Helix

166 – 168

3

Beta strand

170 – 178

9

Helix

183 – 191

9

Beta strand

192 – 194

3

Helix

195 – 204

10

Helix

214 – 225

12

Helix

227 – 229

3

Beta strand

236 – 239

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 6, 2007. Version 2. Checksum: A6E10E9DF9304107	FASTA	245	26,724
	10 20 30 40 50 60 MGRLDGKVII LTAAAQGIGQ AAALAFAREG AKVIATDINE SKLQELEKYP GIQTRVLDVT 70 80 90 100 110 120 KKKQIDQFAN EVERLDVLFN VAGFVHHGTV LDCEEKDWDF SMNLNVRSMY LMIKAFLPKM 130 140 150 160 170 180 LAQKSGNIIN MSSVASSVKG VVNRCVYSTT KAAVIGLTKS VAADFIQQGI RCNCVCPGTV 190 200 210 220 230 240 DTPSLQERIQ ARGNPEEARN DFLKRQKTGR FATAEEIAML CVYLASDESA YVTGNPVIID GGWSL
	Isoform 2. Checksum: 23BD76240A349C5F	FASTA	173	19,209
	10 20 30 40 50 60 MGRLDGKVII LTAAAQGIGQ AAALAFAREG AKVIATDINE SKLQELEKYP GIQTRVLDVT 70 80 90 100 110 120 KKKQIDQFAN EVERLDVLFN VAGFVHHGTV LDCEEKDWDF SMNLNVRSMY LMIKAFLPKM 130 140 150 160 170 LAQKSGNIIN MSSVASSVKG GSVSFRGLRC SYTHIIKSSA FGNRHSRDYN FKY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed: 10931946] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Hypothalamus.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-70.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT SER-70.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Ovary.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT SER-70. Tissue: Brain and Skin.
[6]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132, MASS SPECTROMETRY.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-48, MASS SPECTROMETRY.
[9]	"Characterization of human DHRS6, an orphan short chain dehydrogenase/reductase enzyme: a novel, cytosolic type 2 R-beta-hydroxybutyrate dehydrogenase." Guo K., Lukacik P., Papagrigoriou E., Meier M., Lee W.H., Adamski J., Oppermann U. J. Biol. Chem. 281:10291-10297(2006) [PubMed: 16380372] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) IN COMPLEX WITH NAD, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, SUBCELLULAR LOCATION, SUBUNIT.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF164790 mRNA. Translation: AAF80754.1.
AY358841 mRNA. Translation: AAQ89200.1.
CR457309 mRNA. Translation: CAG33590.1.
AK023323 mRNA. Translation: BAB14526.1.
BC037277 mRNA. Translation: AAH37277.1.
BC001953 mRNA. Translation: AAH01953.1.
BC095414 mRNA. Translation: AAH95414.1.

IPI

IPI00446769.
IPI00607799.

RefSeq

NP_064524.3.

UniGene

Hs.124696

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AG5	X-ray	1.84	A/B/C/D	1-245	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q9BUT1.

PTM databases

PhosphoSite

Q9BUT1.

Proteomic databases

PRIDE

Q9BUT1.

Genome annotation databases

Ensembl

ENST00000296424; ENSP00000296424; ENSG00000164039; Homo sapiens. [Genome view]
ENST00000432053; ENSP00000409176; ENSG00000164039; Homo sapiens. [Genome view]

GeneID

56898.

KEGG

hsa:56898.

UCSC

uc003hwz.1. human.

Organism-specific databases

CTD

56898.

GeneCards

GC04M104218.

H-InvDB

HIX0004415.

HGNC

HGNC:32389. BDH2.

PharmGKB

PA142672559.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9BUT1.

HOVERGEN

Q9BUT1.

OMA

ERIDVLF.

Enzyme and pathway databases

BRENDA

1.1.1.30. 247.

Gene expression databases

ArrayExpress

Q9BUT1.

Bgee

Q9BUT1.

CleanEx

HS_BDH2.

Genevestigator

Q9BUT1.

GermOnline

ENSG00000164039. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

PANTHER

PTHR19410. ADH_short_C2. 1 hit.

Pfam

PF00106. adh_short. 1 hit.
[Graphical view]

PRINTS

PR00081. GDHRDH.
PR00080. SDRFAMILY.

PROSITE

PS00061. ADH_SHORT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

62339.

Entry information

Entry name

BDH2_HUMAN

Accession

Primary (citable) accession number: Q9BUT1
Secondary accession number(s): Q503A0 , Q6IA46, Q6UWD3, Q9H8S8, Q9NRX8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	February 6, 2007
Last modified:	November 3, 2009
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.