AL9A1_HUMAN
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 03-AUG-2022, entry version 194.
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:30914451, ECO:0000269|PubMed:8645224};
DE AltName: Full=Gamma-aminobutyraldehyde dehydrogenase {ECO:0000303|PubMed:10702312};
DE EC=1.2.1.19 {ECO:0000269|PubMed:10702312, 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; 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 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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18] {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. {ECO:0000269|PubMed:10702312, 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:30914451, 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:30914451,
CC ECO:0000269|PubMed:8645224};
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 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}.
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}.
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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; 52.
DR IntAct; P49189; 10.
DR MINT; P49189; -.
DR STRING; 9606.ENSP00000346827; -.
DR ChEMBL; CHEMBL3542434; -.
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; P49189; -.
DR PeptideAtlas; P49189; -.
DR PRIDE; P49189; -.
DR ProteomicsDB; 5480; -.
DR ProteomicsDB; 55968; -. [P49189-1]
DR Antibodypedia; 1661; 262 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 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; GMKYVTM; -.
DR OrthoDB; 538179at2759; -.
DR PhylomeDB; P49189; -.
DR TreeFam; TF314257; -.
DR BioCyc; MetaCyc:HS06992-MON; -.
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 UniPathway; UPA00118; -.
DR BioGRID-ORCS; 223; 46 hits in 1081 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 99 other tissues.
DR Genevisible; P49189; HS.
DR GO; GO:0005737; C:cytoplasm; TAS: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:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC.
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:0042445; P:hormone metabolic process; TAS:UniProtKB.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR DisProt; DP02783; -.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 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 Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
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
