BDH_HUMAN
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 03-AUG-2022, entry version 198.
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; 71.
DR IntAct; Q02338; 17.
DR STRING; 9606.ENSP00000376184; -.
DR DrugBank; DB00157; NADH.
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; Q02338; -.
DR PeptideAtlas; Q02338; -.
DR PRIDE; Q02338; -.
DR ProteomicsDB; 58082; -.
DR TopDownProteomics; Q02338; -.
DR Antibodypedia; 33961; 249 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 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; FAGCFLK; -.
DR OrthoDB; 1390068at2759; -.
DR PhylomeDB; Q02338; -.
DR TreeFam; TF325617; -.
DR BioCyc; MetaCyc:HS08579-MON; -.
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; 11 hits in 1073 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 100 other tissues.
DR ExpressionAtlas; Q02338; baseline and differential.
DR Genevisible; Q02338; HS.
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:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
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
