ID   BDH_HUMAN               Reviewed;         343 AA.
AC   Q02338; D3DXC0; Q96ET1; Q9BRZ4;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   15-NOV-2002, sequence version 3.
DT   27-MAR-2024, entry version 207.
DE   RecName: Full=D-beta-hydroxybutyrate dehydrogenase, mitochondrial {ECO:0000305};
DE            EC=1.1.1.30 {ECO:0000250|UniProtKB:P29147};
DE   AltName: Full=3-hydroxybutyrate dehydrogenase {ECO:0000303|PubMed:1639787};
DE            Short=BDH {ECO:0000303|PubMed:1639787};
DE   AltName: Full=Short chain dehydrogenase/reductase family 9C member 1;
DE   Flags: Precursor;
GN   Name=BDH1 {ECO:0000312|HGNC:HGNC:1027};
GN   Synonyms=BDH {ECO:0000303|PubMed:1639787}, SDR9C1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Heart;
RX   PubMed=1639787; DOI=10.1016/s0021-9258(19)49556-2;
RA   Marks A.R., McIntyre J.O., Duncan T.M., Erdjument-Bromage H., Tempst P.,
RA   Fleischer S.;
RT   "Molecular cloning and characterization of (R)-3-hydroxybutyrate
RT   dehydrogenase from human heart.";
RL   J. Biol. Chem. 267:15459-15463(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung, and Ovary;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [5]
RP   CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER TYR-46, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(R)-3-hydroxybutanoate + NAD(+) = acetoacetate + H(+) + NADH;
CC         Xref=Rhea:RHEA:20521, ChEBI:CHEBI:10983, ChEBI:CHEBI:13705,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.30;
CC         Evidence={ECO:0000250|UniProtKB:P29147};
CC   -!- ACTIVITY REGULATION: Requires phosphatidylcholine as an allosteric
CC       activator for enzymatic activity. {ECO:0000250|UniProtKB:Q02337}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q02337}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000250|UniProtKB:Q02337}. Mitochondrion matrix
CC       {ECO:0000250|UniProtKB:Q02337}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA58352.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; M93107; AAA58352.1; ALT_FRAME; mRNA.
DR   EMBL; CH471191; EAW53606.1; -; Genomic_DNA.
DR   EMBL; CH471191; EAW53607.1; -; Genomic_DNA.
DR   EMBL; CH471191; EAW53608.1; -; Genomic_DNA.
DR   EMBL; CH471191; EAW53609.1; -; Genomic_DNA.
DR   EMBL; BC005844; AAH05844.1; -; mRNA.
DR   EMBL; BC011964; AAH11964.1; -; mRNA.
DR   EMBL; BC019317; AAH19317.1; -; mRNA.
DR   CCDS; CCDS3328.1; -.
DR   PIR; A42845; A42845.
DR   RefSeq; NP_004042.1; NM_004051.4.
DR   RefSeq; NP_976059.1; NM_203314.2.
DR   RefSeq; NP_976060.1; NM_203315.2.
DR   RefSeq; XP_005269409.1; XM_005269352.3.
DR   RefSeq; XP_016862496.1; XM_017007007.1.
DR   AlphaFoldDB; Q02338; -.
DR   SMR; Q02338; -.
DR   BioGRID; 107091; 78.
DR   IntAct; Q02338; 17.
DR   STRING; 9606.ENSP00000376184; -.
DR   DrugBank; DB00157; NADH.
DR   GlyCosmos; Q02338; 1 site, No reported glycans.
DR   GlyGen; Q02338; 1 site.
DR   iPTMnet; Q02338; -.
DR   PhosphoSitePlus; Q02338; -.
DR   SwissPalm; Q02338; -.
DR   BioMuta; BDH1; -.
DR   DMDM; 25108876; -.
DR   EPD; Q02338; -.
DR   jPOST; Q02338; -.
DR   MassIVE; Q02338; -.
DR   MaxQB; Q02338; -.
DR   PaxDb; 9606-ENSP00000376184; -.
DR   PeptideAtlas; Q02338; -.
DR   ProteomicsDB; 58082; -.
DR   Pumba; Q02338; -.
DR   TopDownProteomics; Q02338; -.
DR   Antibodypedia; 33961; 293 antibodies from 30 providers.
DR   DNASU; 622; -.
DR   Ensembl; ENST00000358186.6; ENSP00000350914.2; ENSG00000161267.12.
DR   Ensembl; ENST00000392378.6; ENSP00000376183.2; ENSG00000161267.12.
DR   Ensembl; ENST00000392379.6; ENSP00000376184.1; ENSG00000161267.12.
DR   Ensembl; ENST00000612690.3; ENSP00000484421.1; ENSG00000275544.4.
DR   Ensembl; ENST00000617317.2; ENSP00000482744.1; ENSG00000275544.4.
DR   GeneID; 622; -.
DR   KEGG; hsa:622; -.
DR   MANE-Select; ENST00000392379.6; ENSP00000376184.1; NM_203314.3; NP_976059.1.
DR   UCSC; uc003fxr.3; human.
DR   AGR; HGNC:1027; -.
DR   CTD; 622; -.
DR   DisGeNET; 622; -.
DR   GeneCards; BDH1; -.
DR   HGNC; HGNC:1027; BDH1.
DR   HPA; ENSG00000161267; Tissue enriched (liver).
DR   MIM; 603063; gene.
DR   neXtProt; NX_Q02338; -.
DR   OpenTargets; ENSG00000161267; -.
DR   PharmGKB; PA25331; -.
DR   VEuPathDB; HostDB:ENSG00000161267; -.
DR   eggNOG; KOG1610; Eukaryota.
DR   GeneTree; ENSGT00940000156929; -.
DR   InParanoid; Q02338; -.
DR   OMA; RYEMHRW; -.
DR   OrthoDB; 5403248at2759; -.
DR   PhylomeDB; Q02338; -.
DR   TreeFam; TF325617; -.
DR   BioCyc; MetaCyc:HS08579-MONOMER; -.
DR   PathwayCommons; Q02338; -.
DR   Reactome; R-HSA-77108; Utilization of Ketone Bodies.
DR   Reactome; R-HSA-77111; Synthesis of Ketone Bodies.
DR   SignaLink; Q02338; -.
DR   BioGRID-ORCS; 622; 15 hits in 1154 CRISPR screens.
DR   ChiTaRS; BDH1; human.
DR   GeneWiki; BDH1; -.
DR   GenomeRNAi; 622; -.
DR   Pharos; Q02338; Tbio.
DR   PRO; PR:Q02338; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q02338; Protein.
DR   Bgee; ENSG00000161267; Expressed in right lobe of liver and 102 other cell types or tissues.
DR   ExpressionAtlas; Q02338; baseline and differential.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0099617; C:matrix side of mitochondrial inner membrane; ISS:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0003858; F:3-hydroxybutyrate dehydrogenase activity; IDA:UniProtKB.
DR   GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
DR   CDD; cd09805; type2_17beta_HSD-like_SDR_c; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR   InterPro; IPR002347; SDR_fam.
DR   PANTHER; PTHR43313:SF25; D-BETA-HYDROXYBUTYRATE DEHYDROGENASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR43313; SHORT-CHAIN DEHYDROGENASE/REDUCTASE FAMILY 9C; 1.
DR   Pfam; PF00106; adh_short; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   PRINTS; PR00080; SDRFAMILY.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00061; ADH_SHORT; 1.
DR   Genevisible; Q02338; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Allosteric enzyme; Glycoprotein; Lipid metabolism; Membrane;
KW   Mitochondrion; Mitochondrion inner membrane; NAD; Oxidoreductase;
KW   Phosphoprotein; Reference proteome; Transit peptide.
FT   TRANSIT         1..46
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0007744|PubMed:25944712"
FT   CHAIN           47..343
FT                   /note="D-beta-hydroxybutyrate dehydrogenase, mitochondrial"
FT                   /id="PRO_0000031960"
FT   ACT_SITE        208
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT   BINDING         59..83
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         195
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         73
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q80XN0"
FT   MOD_RES         97
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q80XN0"
FT   MOD_RES         132
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q80XN0"
FT   MOD_RES         177
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q80XN0"
FT   MOD_RES         212
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q80XN0"
FT   MOD_RES         246
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P29147"
FT   MOD_RES         258
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q80XN0"
FT   MOD_RES         259
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q80XN0"
FT   MOD_RES         259
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q80XN0"
FT   MOD_RES         280
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q80XN0"
FT   CARBOHYD        219
FT                   /note="O-linked (GlcNAc) serine"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        70
FT                   /note="S -> A (in Ref. 3; AAH11964)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        115..116
FT                   /note="CS -> FR (in Ref. 1; AAA58352)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        249
FT                   /note="S -> N (in Ref. 1; AAA58352)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   343 AA;  38157 MW;  B8AA1148111ACA8F CRC64;
     MLATRLSRPL SRLPGKTLSA CDRENGARRP LLLGSTSFIP IGRRTYASAA EPVGSKAVLV
     TGCDSGFGFS LAKHLHSKGF LVFAGCLMKD KGHDGVKELD SLNSDRLRTV QLNVCSSEEV
     EKVVEIVRSS LKDPEKGMWG LVNNAGISTF GEVEFTSLET YKQVAEVNLW GTVRMTKSFL
     PLIRRAKGRV VNISSMLGRM ANPARSPYCI TKFGVEAFSD CLRYEMYPLG VKVSVVEPGN
     FIAATSLYSP ESIQAIAKKM WEELPEVVRK DYGKKYFDEK IAKMETYCSS GSTDTSPVID
     AVTHALTATT PYTRYHPMDY YWWLRMQIMT HLPGAISDMI YIR
//