ID AL9A1_HUMAN Reviewed; 494 AA. AC P49189; B2R6X1; B4DXY7; B9EKV4; Q5VV90; Q6LCL1; Q9NZT7; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-2005, sequence version 3. DT 27-MAR-2024, entry version 203. DE RecName: Full=4-trimethylaminobutyraldehyde dehydrogenase; DE Short=TMABA-DH {ECO:0000303|PubMed:10702312}; DE Short=TMABALDH {ECO:0000303|PubMed:30914451}; DE EC=1.2.1.47 {ECO:0000269|PubMed:10702312, ECO:0000269|PubMed:30914451, ECO:0000269|PubMed:8645224}; DE AltName: Full=Aldehyde dehydrogenase E3 isozyme {ECO:0000303|PubMed:8645224}; DE AltName: Full=Aldehyde dehydrogenase family 9 member A1; DE EC=1.2.1.3 {ECO:0000269|PubMed:10702312, ECO:0000269|PubMed:1799975, ECO:0000269|PubMed:30914451, ECO:0000269|PubMed:8645224}; DE AltName: Full=Formaldehyde dehydrogenase; DE EC=1.2.1.46 {ECO:0000269|PubMed:1799975}; DE AltName: Full=Gamma-aminobutyraldehyde dehydrogenase {ECO:0000303|PubMed:10702312}; DE EC=1.2.1.19 {ECO:0000269|PubMed:10702312, ECO:0000269|PubMed:1799975, ECO:0000269|PubMed:30914451, ECO:0000269|PubMed:8645224}; DE AltName: Full=R-aminobutyraldehyde dehydrogenase; DE Contains: DE RecName: Full=4-trimethylaminobutyraldehyde dehydrogenase, N-terminally processed; GN Name=ALDH9A1; GN Synonyms=ALDH4, ALDH7, ALDH9 {ECO:0000303|PubMed:8786138}; 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] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT RP SER-116. RC TISSUE=Liver; RX PubMed=8786138; DOI=10.1006/geno.1996.0300; RA Lin S.W., Chen J.C., Hsu L.C., Hsieh C.-L., Yoshida A.; RT "Human gamma-aminobutyraldehyde dehydrogenase (ALDH9): cDNA sequence, RT genomic organization, polymorphism, chromosomal localization, and tissue RT expression."; RL Genomics 34:376-380(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY. RC 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Spleen, and Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). 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 [7] RP PROTEIN SEQUENCE OF 2-15; 247-258; 299-310; 315-326 AND 472-481, CLEAVAGE RP OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Heiserich L., Gottlieb E.; RL Submitted (MAR-2008) to UniProtKB. RN [8] RP PROTEIN SEQUENCE OF 259-274; 353-366; 412-426 AND 434-453, NUCLEOTIDE RP SEQUENCE [MRNA] OF 29-494, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL RP PROPERTIES, TISSUE SPECIFICITY, AND VARIANT SER-116. RC TISSUE=Brain; RX PubMed=8645224; DOI=10.1042/bj3160317; RA Kikonyogo A., Pietruszko R.; RT "Aldehyde dehydrogenase from adult human brain that dehydrogenates gamma- RT aminobutyraldehyde: purification, characterization, cloning and RT distribution."; RL Biochem. J. 316:317-324(1996). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 33-494 (ISOFORM 1), AND PARTIAL PROTEIN RP SEQUENCE. RX PubMed=8269919; DOI=10.1111/j.1432-1033.1993.tb18379.x; RA Kurys G., Shah P.C., Kikonyogo A., Reed D., Ambroziak W., Pietruszko R.; RT "Human aldehyde dehydrogenase. cDNA cloning and primary structure of the RT enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde."; RL Eur. J. Biochem. 218:311-320(1993). RN [10] RP CHARACTERIZATION. RC TISSUE=Liver; RX PubMed=2925663; DOI=10.1016/s0021-9258(18)83802-9; RA Kurys G., Ambroziak W., Pietruszko R.; RT "Human aldehyde dehydrogenase. Purification and characterization of a third RT isozyme with low Km for gamma-aminobutyraldehyde."; RL J. Biol. Chem. 264:4715-4721(1989). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. 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). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=2071588; DOI=10.1016/s0021-9258(18)98796-x; RA Ambroziak W., Pietruszko R.; RT "Human aldehyde dehydrogenase. Activity with aldehyde metabolites of RT monoamines, diamines, and polyamines."; RL J. Biol. Chem. 266:13011-13018(1991). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-298, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [18] 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 [19] 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). RN [20] {ECO:0007744|PDB:6QAK, ECO:0007744|PDB:6QAO, ECO:0007744|PDB:6QAP} RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND PATHWAY. RX PubMed=30914451; DOI=10.1042/bsr20190558; RA Koncitikova R., Vigouroux A., Kopecna M., Sebela M., Morera S., Kopecny D.; RT "Kinetic and structural analysis of human ALDH9A1."; RL Biosci. Rep. 0:0-0(2019). 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, ECO:0000269|PubMed:30914451, CC ECO:0000269|PubMed:8645224}. 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, ECO:0000269|PubMed:30914451, CC ECO:0000269|PubMed:8645224}; 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, ECO:0000269|PubMed:30914451, CC ECO:0000269|PubMed:8645224}; 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 ECO:0000269|PubMed:30914451, ECO:0000269|PubMed:8645224}; 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:0000269|PubMed:1799975}; 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; Evidence={ECO:0000269|PubMed:1799975}; 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:0000269|PubMed:1799975}; 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:0000269|PubMed:1799975}; 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:0000269|PubMed:1799975}; 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:0000269|PubMed:1799975}; 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:0000269|PubMed:1799975}; 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:0000269|PubMed:1799975}; 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:0000269|PubMed:1799975}; 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:0000269|PubMed:1799975}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=68 uM for NAD {ECO:0000269|PubMed:10702312}; CC KM=32 uM for NAD {ECO:0000269|PubMed:30914451}; CC KM=4695 uM for NADP {ECO:0000269|PubMed:10702312}; CC KM=4.8 uM for gamma-trimethylaminobutyraldehyde CC {ECO:0000269|PubMed:10702312}; CC KM=7 uM for gamma-trimethylaminobutyraldehyde CC {ECO:0000269|PubMed:8645224}; CC KM=6 uM for gamma-trimethylaminobutyraldehyde CC {ECO:0000269|PubMed:30914451}; CC KM=53 uM for 3-trimethylaminopropanal {ECO:0000269|PubMed:30914451}; CC KM=28 uM for 4-aminobutyraldehyde {ECO:0000269|PubMed:10702312}; CC KM=67 uM for 4-aminobutyraldehyde {ECO:0000269|PubMed:30914451}; CC KM=70 uM for 4-aminobutyraldehyde {ECO:0000269|PubMed:8645224}; CC KM=7 uM for heptanal {ECO:0000269|PubMed:10702312}; CC KM=7 uM for octanal {ECO:0000269|PubMed:10702312}; CC KM=11 uM for 4-aminobutyraldehyde; CC KM=59 uM for 5-hydroxyindole-3-acetaldehyde CC {ECO:0000269|PubMed:1799975}; CC KM=4.9 uM for acrolein {ECO:0000269|PubMed:1799975}; CC KM=2.6 uM for 3,4-dihydroxyphenylacetaldehyde CC {ECO:0000269|PubMed:1799975}; CC KM=4.6 uM for 4-aminobutyraldehyde {ECO:0000269|PubMed:1799975}; CC KM=410 uM for formaldehyde {ECO:0000269|PubMed:1799975}; CC KM=57 uM for acetaldehyde {ECO:0000269|PubMed:1799975}; CC KM=9.5 uM for propionaldehyde {ECO:0000269|PubMed:1799975}; CC KM=2.8 uM for butyraldehyde {ECO:0000269|PubMed:1799975}; CC KM=1.4 uM for pentaldehyde {ECO:0000269|PubMed:1799975}; CC KM=0.6 uM for hexanaldehyde {ECO:0000269|PubMed:1799975}; CC pH dependence: CC Optimum pH is about 9.4 with propionaldehyde as substrate, and 7.5 CC with 4-aminobutyraldehyde as substrate.; CC -!- PATHWAY: Amine and polyamine biosynthesis; carnitine biosynthesis. CC {ECO:0000305|PubMed:10702312, ECO:0000305|PubMed:30914451}. CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:30914451}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q9JLJ3}. Cytoplasm {ECO:0000269|PubMed:1799975}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=3; CC Name=1; CC IsoId=P49189-1; Sequence=Displayed; CC Name=2; CC IsoId=P49189-2; Sequence=VSP_056305; CC Name=3; CC IsoId=P49189-3; Sequence=VSP_060045; CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level) CC (PubMed:8645224). High expression in adult liver, skeletal muscle, and CC kidney. Low levels in heart, pancreas, lung and brain (PubMed:8786138). CC Expressed in all regions of the brain. Expression levels are variable CC in the different brain areas, with the highest levels in the spinal CC cord and the lowest in the occipital pole. {ECO:0000269|PubMed:8645224, CC ECO:0000269|PubMed:8786138}. CC -!- DEVELOPMENTAL STAGE: Strongly expressed in human embryonic brain CC (gestational age 12 weeks). CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative initiation. CC Contains a predicted signal peptide at positions 1-24. {ECO:0000305}. 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; U34252; AAB18827.1; -; mRNA. DR EMBL; AF172093; AAF43600.1; -; mRNA. DR EMBL; AK302183; BAG63549.1; -; mRNA. DR EMBL; AK302191; BAG63554.1; -; mRNA. DR EMBL; AK312751; BAG35618.1; -; mRNA. DR EMBL; AL451074; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW90758.1; -; Genomic_DNA. DR EMBL; BC151140; AAI51141.1; -; mRNA. DR EMBL; BC151141; AAI51142.1; -; mRNA. DR EMBL; U50203; AAB06721.1; -; mRNA. DR EMBL; X75425; CAA53176.1; -; mRNA. DR CCDS; CCDS1250.2; -. [P49189-3] DR PIR; G02054; S39532. DR RefSeq; NP_000687.3; NM_000696.3. [P49189-3] DR RefSeq; XP_011507596.1; XM_011509294.2. DR PDB; 6QAK; X-ray; 2.50 A; A/B/C/D/E/F/G/H=1-494. DR PDB; 6QAO; X-ray; 2.89 A; A/B/C/D/E/F/G/H=1-494. DR PDB; 6QAP; X-ray; 2.30 A; A/B/C/D=1-494. DR PDB; 6VR6; X-ray; 2.50 A; A/B/C/D/E/F/G/H=2-494. DR PDB; 6VWF; X-ray; 2.64 A; A/B=1-494. DR PDBsum; 6QAK; -. DR PDBsum; 6QAO; -. DR PDBsum; 6QAP; -. DR PDBsum; 6VR6; -. DR PDBsum; 6VWF; -. DR AlphaFoldDB; P49189; -. DR SASBDB; P49189; -. DR SMR; P49189; -. DR BioGRID; 106725; 80. DR IntAct; P49189; 11. DR MINT; P49189; -. DR STRING; 9606.ENSP00000346827; -. DR ChEMBL; CHEMBL2542; -. DR DrugBank; DB00157; NADH. DR GlyGen; P49189; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P49189; -. DR MetOSite; P49189; -. DR PhosphoSitePlus; P49189; -. DR SwissPalm; P49189; -. DR BioMuta; ALDH9A1; -. DR DMDM; 62511242; -. DR REPRODUCTION-2DPAGE; IPI00479877; -. DR CPTAC; CPTAC-309; -. DR CPTAC; CPTAC-310; -. DR EPD; P49189; -. DR jPOST; P49189; -. DR MassIVE; P49189; -. DR MaxQB; P49189; -. DR PaxDb; 9606-ENSP00000346827; -. DR PeptideAtlas; P49189; -. DR ProteomicsDB; 5480; -. DR ProteomicsDB; 55968; -. [P49189-1] DR Pumba; P49189; -. DR Antibodypedia; 1661; 284 antibodies from 32 providers. DR DNASU; 223; -. DR Ensembl; ENST00000354775.5; ENSP00000346827.4; ENSG00000143149.13. [P49189-3] DR GeneID; 223; -. DR KEGG; hsa:223; -. DR MANE-Select; ENST00000354775.5; ENSP00000346827.4; NM_000696.4; NP_000687.3. [P49189-3] DR UCSC; uc001gdh.2; human. [P49189-1] DR AGR; HGNC:412; -. DR CTD; 223; -. DR DisGeNET; 223; -. DR GeneCards; ALDH9A1; -. DR HGNC; HGNC:412; ALDH9A1. DR HPA; ENSG00000143149; Low tissue specificity. DR MIM; 602733; gene. DR neXtProt; NX_P49189; -. DR OpenTargets; ENSG00000143149; -. DR PharmGKB; PA24706; -. DR VEuPathDB; HostDB:ENSG00000143149; -. DR eggNOG; KOG2450; Eukaryota. DR GeneTree; ENSGT00940000163309; -. DR HOGENOM; CLU_005391_0_0_1; -. DR InParanoid; P49189; -. DR OMA; CREGIRM; -. DR OrthoDB; 2291791at2759; -. DR PhylomeDB; P49189; -. DR TreeFam; TF314257; -. DR BioCyc; MetaCyc:HS06992-MONOMER; -. DR BRENDA; 1.2.1.47; 2681. DR PathwayCommons; P49189; -. DR Reactome; R-HSA-71262; Carnitine synthesis. DR SABIO-RK; P49189; -. DR SignaLink; P49189; -. DR SIGNOR; P49189; -. DR UniPathway; UPA00118; -. DR BioGRID-ORCS; 223; 46 hits in 1160 CRISPR screens. DR ChiTaRS; ALDH9A1; human. DR GeneWiki; Aldehyde_dehydrogenase_9_family,_member_A1; -. DR GenomeRNAi; 223; -. DR Pharos; P49189; Tbio. DR PRO; PR:P49189; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P49189; Protein. DR Bgee; ENSG00000143149; Expressed in right adrenal gland cortex and 101 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0033737; F:1-pyrroline dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0047105; F:4-trimethylammoniobutyraldehyde dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:UniProtKB. DR GO; GO:0019145; F:aminobutyraldehyde dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0018467; F:formaldehyde dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC. DR GO; GO:0036094; F:small molecule binding; EXP:DisProt. DR GO; GO:0045329; P:carnitine biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0006081; P:cellular aldehyde metabolic process; IDA:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR CDD; cd07090; ALDH_F9_TMBADH; 1. DR DisProt; DP02783; -. 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. DR Genevisible; P49189; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative initiation; Alternative splicing; KW Cytoplasm; Direct protein sequencing; NAD; Oxidoreductase; KW Reference proteome. FT CHAIN 1..494 FT /note="4-trimethylaminobutyraldehyde dehydrogenase" FT /id="PRO_0000434351" FT INIT_MET 1 FT /note="Removed; alternate" FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..494 FT /note="4-trimethylaminobutyraldehyde dehydrogenase, N- FT terminally processed" FT /id="PRO_0000056485" FT ACT_SITE 254 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007, FT ECO:0000255|PROSITE-ProRule:PRU10008" FT ACT_SITE 288 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007, FT 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 SITE 157 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylserine; in 4-trimethylaminobutyraldehyde FT dehydrogenase, N-terminally processed" FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" 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:0007744|PubMed:19608861" FT MOD_RES 303 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9JLJ2" FT MOD_RES 303 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9JLJ2" FT MOD_RES 344 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9JLJ2" FT VAR_SEQ 1..70 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056305" FT VAR_SEQ 1 FT /note="M -> MFLRAGLAALSPLLRSLRPSPVAAM (in isoform 3)" FT /id="VSP_060045" FT VARIANT 116 FT /note="C -> S (in allele ALDH9A1*2)" FT /evidence="ECO:0000269|PubMed:8645224, FT ECO:0000269|PubMed:8786138" FT /id="VAR_011304" FT CONFLICT 19..25 FT /note="RVEPADA -> AGAGGR (in Ref. 1; AAB18827)" FT /evidence="ECO:0000305" FT CONFLICT 150 FT /note="C -> Q (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 159 FT /note="P -> W (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 172 FT /note="A -> R (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT TURN 3..5 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 12..15 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 18..20 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 23..32 FT /evidence="ECO:0007829|PDB:6QAP" FT TURN 34..36 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 39..46 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 48..65 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 70..86 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 88..99 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 103..126 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 129..133 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 135..137 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 139..146 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 148..153 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 156..158 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 159..172 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 176..180 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 188..199 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 205..208 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 213..221 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 225..229 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 234..247 FT /evidence="ECO:0007829|PDB:6VR6" FT STRAND 251..254 FT /evidence="ECO:0007829|PDB:6VR6" FT STRAND 260..263 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 265..267 FT /evidence="ECO:0007829|PDB:6QAO" FT HELIX 269..281 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 282..285 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 287..290 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 293..297 FT /evidence="ECO:0007829|PDB:6QAP" FT TURN 298..300 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 301..312 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 333..348 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 352..355 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 365..367 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 376..380 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 386..389 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 394..402 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 405..412 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 419..424 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 428..437 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 441..446 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 457..459 FT /evidence="ECO:0007829|PDB:6QAP" FT HELIX 461..463 FT /evidence="ECO:0007829|PDB:6VR6" FT HELIX 468..476 FT /evidence="ECO:0007829|PDB:6QAP" FT STRAND 478..485 FT /evidence="ECO:0007829|PDB:6QAP" SQ SEQUENCE 494 AA; 53802 MW; 1E1CDF910D763BA1 CRC64; MSTGTFVVSQ PLNYRGGARV EPADASGTEK AFEPATGRVI ATFTCSGEKE VNLAVQNAKA AFKIWSQKSG MERCRILLEA ARIIREREDE IATMECINNG KSIFEARLDI DISWQCLEYY AGLAASMAGE HIQLPGGSFG YTRREPLGVC VGIGAWNYPF QIASWKSAPA LACGNAMVFK PSPFTPVSAL LLAEIYSEAG VPPGLFNVVQ GGAATGQFLC QHPDVAKVSF TGSVPTGMKI MEMSAKGIKP VTLELGGKSP LIIFSDCDMN NAVKGALMAN FLTQGQVCCN GTRVFVQKEI LDKFTEEVVK QTQRIKIGDP LLEDTRMGPL INRPHLERVL GFVKVAKEQG AKVLCGGDIY VPEDPKLKDG YYMRPCVLTN CRDDMTCVKE EIFGPVMSIL SFDTEAEVLE RANDTTFGLA AGVFTRDIQR AHRVVAELQA GTCFINNYNV SPVELPFGGY KKSGFGRENG RVTIEYYSQL KTVCVEMGDV ESAF //