ID AL9A1_RAT Reviewed; 494 AA. AC Q9JLJ3; Q6GMM4; DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 27-MAR-2024, entry version 146. DE RecName: Full=4-trimethylaminobutyraldehyde dehydrogenase; DE Short=TMABA-DH {ECO:0000303|PubMed:10702312}; DE Short=TMABADH; DE EC=1.2.1.47 {ECO:0000269|PubMed:10702312}; DE AltName: Full=Aldehyde dehydrogenase family 9 member A1; DE EC=1.2.1.3 {ECO:0000269|PubMed:10702312, ECO:0000269|PubMed:1799975}; DE AltName: Full=Formaldehyde dehydrogenase; DE EC=1.2.1.46 {ECO:0000250|UniProtKB:P49189}; DE AltName: Full=Gamma-aminobutyraldehyde dehydrogenase {ECO:0000303|PubMed:10702312}; DE EC=1.2.1.19 {ECO:0000269|PubMed:10702312, ECO:0000269|PubMed:1799975}; GN Name=Aldh9a1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC RP ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RC STRAIN=Wistar; TISSUE=Liver; RX PubMed=10702312; DOI=10.1074/jbc.275.10.7390; RA Vaz F.M., Fouchier S.W., Ofman R., Sommer M., Wanders R.J.A.; RT "Molecular and biochemical characterization of rat gamma- RT trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement RT of human aldehyde dehydrogenase 9 in carnitine biosynthesis."; RL J. Biol. Chem. 275:7390-7394(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; 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 [3] RP PROTEIN SEQUENCE OF 50-59; 199-223; 275-293 AND 412-426, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Spinal cord; RA Lubec G., Afjehi-Sadat L., Kang S.U.; RL Submitted (JUL-2007) to UniProtKB. RN [4] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=1799975; DOI=10.1016/0305-0491(91)90382-n; RA Ambroziak W., Kurys G., Pietruszko R.; RT "Aldehyde dehydrogenase (EC 1.2.1.3): comparison of subcellular RT localization of the third isozyme that dehydrogenates gamma- RT aminobutyraldehyde in rat, guinea pig and human liver."; RL Comp. Biochem. Physiol. 100:321-327(1991). CC -!- FUNCTION: Converts gamma-trimethylaminobutyraldehyde into gamma- CC butyrobetaine with high efficiency (in vitro). Can catalyze the CC irreversible oxidation of a broad range of aldehydes to the CC corresponding acids in an NAD-dependent reaction, but with low CC efficiency. Catalyzes the oxidation of aldehydes arising from biogenic CC amines and polyamines. {ECO:0000269|PubMed:10702312, CC ECO:0000269|PubMed:1799975}. CC -!- CATALYTIC ACTIVITY: CC Reaction=4-(trimethylamino)butanal + H2O + NAD(+) = 4- CC (trimethylamino)butanoate + 2 H(+) + NADH; Xref=Rhea:RHEA:17985, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16244, CC ChEBI:CHEBI:18020, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.47; CC Evidence={ECO:0000269|PubMed:10702312}; CC -!- CATALYTIC ACTIVITY: CC Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH; CC Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; EC=1.2.1.3; Evidence={ECO:0000269|PubMed:10702312, CC ECO:0000269|PubMed:1799975}; CC -!- CATALYTIC ACTIVITY: CC Reaction=4-aminobutanal + H2O + NAD(+) = 4-aminobutanoate + 2 H(+) + CC NADH; Xref=Rhea:RHEA:19105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58264, CC ChEBI:CHEBI:59888; EC=1.2.1.19; CC Evidence={ECO:0000269|PubMed:10702312, ECO:0000269|PubMed:1799975}; CC -!- CATALYTIC ACTIVITY: CC Reaction=formaldehyde + H2O + NAD(+) = formate + 2 H(+) + NADH; CC Xref=Rhea:RHEA:16425, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15740, ChEBI:CHEBI:16842, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; EC=1.2.1.46; CC Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetaldehyde + H2O + NAD(+) = acetate + 2 H(+) + NADH; CC Xref=Rhea:RHEA:25294, ChEBI:CHEBI:15343, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; EC=1.2.1.3; CC Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + imidazole-4-acetaldehyde + NAD(+) = 2 H(+) + imidazole- CC 4-acetate + NADH; Xref=Rhea:RHEA:31059, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:27398, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:57969; CC Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acrolein + H2O + NAD(+) = acrylate + 2 H(+) + NADH; CC Xref=Rhea:RHEA:69084, ChEBI:CHEBI:15368, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:37080, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5-hydroxyindol-3-yl)acetaldehyde + H2O + NAD(+) = (5- CC hydroxyindol-3-yl)acetate + 2 H(+) + NADH; Xref=Rhea:RHEA:31215, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:50157, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62622; CC Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3,4-dihydroxyphenylacetaldehyde + H2O + NAD(+) = 3,4- CC dihydroxyphenylacetate + 2 H(+) + NADH; Xref=Rhea:RHEA:69080, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17612, CC ChEBI:CHEBI:27978, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; CC Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + NAD(+) + spermine monoaldehyde = 2 H(+) + N-(2- CC carboxyethyl)spermidine + NADH; Xref=Rhea:RHEA:69168, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:180903, ChEBI:CHEBI:180913; CC Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + NAD(+) + propanal = 2 H(+) + NADH + propanoate; CC Xref=Rhea:RHEA:67256, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17153, ChEBI:CHEBI:17272, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:1799975}; CC -!- CATALYTIC ACTIVITY: CC Reaction=butanal + H2O + NAD(+) = butanoate + 2 H(+) + NADH; CC Xref=Rhea:RHEA:69088, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15743, ChEBI:CHEBI:17968, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + NAD(+) + pentanal = 2 H(+) + NADH + pentanoate; CC Xref=Rhea:RHEA:69092, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:31011, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:84069; Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + hexanal + NAD(+) = 2 H(+) + hexanoate + NADH; CC Xref=Rhea:RHEA:67276, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17120, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:88528; Evidence={ECO:0000250|UniProtKB:P49189}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=28 uM for NAD {ECO:0000269|PubMed:10702312}; CC KM=4 uM for NAD {ECO:0000269|PubMed:1799975}; CC KM=1630 uM for NADP {ECO:0000269|PubMed:10702312}; CC KM=1.4 uM for gamma-trimethylaminobutyraldehyde CC {ECO:0000269|PubMed:10702312}; CC KM=24 uM for 4-aminobutyraldehyde {ECO:0000269|PubMed:10702312}; CC KM=5 uM for 4-aminobutyraldehyde {ECO:0000269|PubMed:1799975}; CC KM=7 uM for heptanal {ECO:0000269|PubMed:10702312}; CC KM=6 uM for octanal {ECO:0000269|PubMed:10702312}; CC KM=7.5 uM for propanal {ECO:0000269|PubMed:1799975}; CC -!- PATHWAY: Amine and polyamine biosynthesis; carnitine biosynthesis. CC {ECO:0000305|PubMed:10702312}. CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P49189}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10702312}. CC Cytoplasm {ECO:0000269|PubMed:1799975}. CC -!- TISSUE SPECIFICITY: Detected in lever (at protein level). CC {ECO:0000269|PubMed:10702312}. CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF170918; AAF43598.1; -; mRNA. DR EMBL; BC074019; AAH74019.1; -; mRNA. DR RefSeq; NP_071609.2; NM_022273.2. DR AlphaFoldDB; Q9JLJ3; -. DR SMR; Q9JLJ3; -. DR BioGRID; 248957; 1. DR IntAct; Q9JLJ3; 1. DR STRING; 10116.ENSRNOP00000005611; -. DR iPTMnet; Q9JLJ3; -. DR PhosphoSitePlus; Q9JLJ3; -. DR SwissPalm; Q9JLJ3; -. DR jPOST; Q9JLJ3; -. DR PaxDb; 10116-ENSRNOP00000005611; -. DR PeptideAtlas; Q9JLJ3; -. DR GeneID; 64040; -. DR KEGG; rno:64040; -. DR UCSC; RGD:68409; rat. DR AGR; RGD:68409; -. DR CTD; 223; -. DR RGD; 68409; Aldh9a1. DR eggNOG; KOG2450; Eukaryota. DR InParanoid; Q9JLJ3; -. DR OrthoDB; 2291791at2759; -. DR PhylomeDB; Q9JLJ3; -. DR BioCyc; MetaCyc:MONOMER-14430; -. DR BRENDA; 1.2.1.47; 5301. DR Reactome; R-RNO-71262; Carnitine synthesis. DR SABIO-RK; Q9JLJ3; -. DR UniPathway; UPA00118; -. DR PRO; PR:Q9JLJ3; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0033737; F:1-pyrroline dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0047105; F:4-trimethylammoniobutyraldehyde dehydrogenase activity; IDA:RGD. DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:UniProtKB. DR GO; GO:0043176; F:amine binding; IDA:RGD. DR GO; GO:0019145; F:aminobutyraldehyde dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0018467; F:formaldehyde dehydrogenase activity; ISS:UniProtKB. DR GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC. DR GO; GO:0042802; F:identical protein binding; IPI:RGD. DR GO; GO:0051287; F:NAD binding; IDA:RGD. DR GO; GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; ISO:RGD. DR GO; GO:0036094; F:small molecule binding; ISO:RGD. DR GO; GO:0045329; P:carnitine biosynthetic process; ISO:RGD. DR GO; GO:0009437; P:carnitine metabolic process; ISO:RGD. DR GO; GO:0006081; P:cellular aldehyde metabolic process; ISS:UniProtKB. DR GO; GO:0001822; P:kidney development; IEP:RGD. DR GO; GO:0001889; P:liver development; IEP:RGD. DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB. DR CDD; cd07090; ALDH_F9_TMBADH; 1. DR InterPro; IPR016161; Ald_DH/histidinol_DH. DR InterPro; IPR016163; Ald_DH_C. DR InterPro; IPR016160; Ald_DH_CS_CYS. DR InterPro; IPR029510; Ald_DH_CS_GLU. DR InterPro; IPR016162; Ald_DH_N. DR InterPro; IPR015590; Aldehyde_DH_dom. DR PANTHER; PTHR11699:SF228; 4-TRIMETHYLAMINOBUTYRALDEHYDE DEHYDROGENASE; 1. DR PANTHER; PTHR11699; ALDEHYDE DEHYDROGENASE-RELATED; 1. DR Pfam; PF00171; Aldedh; 1. DR SUPFAM; SSF53720; ALDH-like; 1. DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1. DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1. PE 1: Evidence at protein level; KW Acetylation; Cytoplasm; Direct protein sequencing; NAD; Oxidoreductase; KW Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P49189" FT CHAIN 2..494 FT /note="4-trimethylaminobutyraldehyde dehydrogenase" FT /id="PRO_0000056489" FT ACT_SITE 254 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007" FT ACT_SITE 288 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10008" FT BINDING 180 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P56533" FT BINDING 232..236 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P56533" FT BINDING 391 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P56533" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:P49189" FT MOD_RES 30 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9JLJ2" FT MOD_RES 30 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9JLJ2" FT MOD_RES 59 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9JLJ2" FT MOD_RES 298 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P49189" FT CONFLICT 493..494 FT /note="AF -> PFENQ (in Ref. 2; AAH74019)" FT /evidence="ECO:0000305" SQ SEQUENCE 494 AA; 53653 MW; E417BD52D7DF567C CRC64; MSTGTFVVSQ PLNYRGGARV EPVDASGTEK AFEPATGREI ATFKCSGEKE VNLAVENAKA AFKIWSKKSG LERCQVLLEA ARIIKERRDE IAIMETINNG KSIFEARLDV DTSWQCLEYY AGLAASMAGE HIQLPGGSFG YTRREPLGVC LGIGAWNYPF QIACWKSAPA LACGNAMIFK PSPFTPVSAL LLAEIYTKAG APNGLFNVVQ GGAATGQFLC QHRDVAKVSF TGSVPTGMKI MEMAAKGIKP ITLELGGKSP LIIFSDCNMK NAVKGALLAN FLTQGQVCCN GTRVFVQKEI ADAFTKEVVR QTQRIKIGDP LLEDTRMGPL INAPHLERVL GFVRSAKEQG ATVLCGGEPY APEDPKLKHG YYMTPCILTN CTDDMTCVKE EIFGPVMSIL TFETEAEVLE RANDTTFGLA AGVFTRDIQR AHRVAAELQA GTCYINNYNV SPVELPFGGY KKSGFGRENG RVTIEYYSQL KTVCVEMGDV ESAF //