ID AL1A1_HUMAN Reviewed; 501 AA. AC P00352; O00768; Q5SYR1; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 02-SEP-2026, entry version 234. DE RecName: Full=Aldehyde dehydrogenase 1A1 {ECO:0000305|PubMed:19296407}; DE EC=1.2.1.19 {ECO:0000250|UniProtKB:P24549}; DE EC=1.2.1.28 {ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407}; DE EC=1.2.1.3 {ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:15623782, ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407, ECO:0000269|PubMed:22339434, ECO:0000269|PubMed:23444097}; DE EC=1.2.1.36 {ECO:0000269|PubMed:25413692}; DE AltName: Full=3-deoxyglucosone dehydrogenase {ECO:0000305|PubMed:17175089}; DE AltName: Full=ALDH-E1; DE AltName: Full=ALHDII; DE AltName: Full=Aldehyde dehydrogenase family 1 member A1 {ECO:0000312|HGNC:HGNC:402}; DE AltName: Full=Aldehyde dehydrogenase, cytosolic {ECO:0000303|PubMed:2591967}; DE AltName: Full=Retinal dehydrogenase 1 {ECO:0000250|UniProtKB:P51647}; DE Short=RALDH 1 {ECO:0000250|UniProtKB:P51647}; DE Short=RalDH1 {ECO:0000250|UniProtKB:P51647}; GN Name=ALDH1A1 {ECO:0000312|HGNC:HGNC:402}; GN Synonyms=ALDC, ALDH1 {ECO:0000312|HGNC:HGNC:402}, PUMB1 GN {ECO:0000312|HGNC:HGNC:402}; 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 [GENOMIC DNA]. RX PubMed=2591967; DOI=10.1016/0888-7543(89)90127-4; RA Hsu L.C., Chang W.-C., Yoshida A.; RT "Genomic structure of the human cytosolic aldehyde dehydrogenase gene."; RL Genomics 5:857-865(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-121. RC TISSUE=Liver; RX PubMed=8214422; DOI=10.1111/j.1530-0277.1993.tb00849.x; RA Zheng C.F., Wang T.T., Weiner H.; RT "Cloning and expression of the full-length cDNAs encoding human liver class RT 1 and class 2 aldehyde dehydrogenase."; RL Alcohol. Clin. Exp. Res. 17:828-831(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION. RC TISSUE=Lens; RX PubMed=19296407; DOI=10.1080/15287390802706371; RA Xiao T., Shoeb M., Siddiqui M.S., Zhang M., Ramana K.V., Srivastava S.K., RA Vasiliou V., Ansari N.H.; RT "Molecular cloning and oxidative modification of human lens ALDH1A1: RT implication in impaired detoxification of lipid aldehydes."; RL J. Toxicol. Environ. Health Part A 72:577-584(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PHE-177. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [7] 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon; 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 [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6. RX PubMed=8493914; DOI=10.1007/978-1-4615-2904-0_5; RA Yoshida A., Hsu L.C., Yanagawa Y.; RT "Biological role of human cytosolic aldehyde dehydrogenase 1: hormonal RT response, retinal oxidation and implication in testicular feminization."; RL Adv. Exp. Med. Biol. 328:37-44(1993). RN [10] RP PROTEIN SEQUENCE OF 2-501, AND ACETYLATION AT SER-2. RC TISSUE=Liver; RX PubMed=6723659; DOI=10.1111/j.1432-1033.1984.tb08150.x; RA Hempel J., von Bahr-Lindstroem H., Joernvall H.; RT "Aldehyde dehydrogenase from human liver. Primary structure of the RT cytoplasmic isoenzyme."; RL Eur. J. Biochem. 141:21-35(1984). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 162-501. RX PubMed=4015823; DOI=10.1016/0741-8329(85)90024-2; RA Yoshida A., Ikawa M., Hsu L.C., Tani K.; RT "Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases."; RL Alcohol 2:103-106(1985). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 162-501. RC TISSUE=Liver; RX PubMed=2987944; DOI=10.1073/pnas.82.11.3771; RA Hsu L.C., Tani K., Fujiyoshi T., Kurachi K., Yoshida A.; RT "Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2."; RL Proc. Natl. Acad. Sci. U.S.A. 82:3771-3775(1985). RN [13] RP PROTEIN SEQUENCE OF 266-273, ACTIVE SITE, AND NAD-BINDING. RX PubMed=3676276; DOI=10.1021/bi00392a015; RA Abriola D.P., Fields R., Stein S., Mackerell A.D. Jr., Pietruszko R.; RT "Active site of human liver aldehyde dehydrogenase."; RL Biochemistry 26:5679-5684(1987). RN [14] RP PARTIAL PROTEIN SEQUENCE. RC TISSUE=Erythrocyte; RX PubMed=2776714; DOI=10.1159/000469006; RA Agarwal D.P., Cohn P., Goedde H.W., Hempel J.; RT "Aldehyde dehydrogenase from human erythrocytes: structural relationship to RT the liver cytosolic isozyme."; RL Enzyme 42:47-52(1989). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP SUBCELLULAR LOCATION. RX PubMed=12941160; DOI=10.1089/104454903322216671; RA Manzer R., Qamar L., Estey T., Pappa A., Petersen D.R., Vasiliou V.; RT "Molecular cloning and baculovirus expression of the rabbit corneal RT aldehyde dehydrogenase (ALDH1A1) cDNA."; RL DNA Cell Biol. 22:329-338(2003). RN [16] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=15623782; DOI=10.1167/iovs.04-0120; RA Choudhary S., Xiao T., Vergara L.A., Srivastava S., Nees D., RA Piatigorsky J., Ansari N.H.; RT "Role of aldehyde dehydrogenase isozymes in the defense of rat lens and RT human lens epithelial cells against oxidative stress."; RL Invest. Ophthalmol. Vis. Sci. 46:259-267(2005). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE RP SPECIFICITY. RX PubMed=17175089; DOI=10.1016/j.biochi.2006.11.005; RA Collard F., Vertommen D., Fortpied J., Duester G., Van Schaftingen E.; RT "Identification of 3-deoxyglucosone dehydrogenase as aldehyde dehydrogenase RT 1A1 (retinaldehyde dehydrogenase 1)."; RL Biochimie 89:369-373(2007). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-91; LYS-128; LYS-252; LYS-353; RP LYS-367; LYS-410; LYS-419; LYS-435 AND LYS-495, 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 [19] 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 [20] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=22339434; DOI=10.1021/tx2005184; RA Yoval-Sanchez B., Rodriguez-Zavala J.S.; RT "Differences in susceptibility to inactivation of human aldehyde RT dehydrogenases by lipid peroxidation byproducts."; RL Chem. Res. Toxicol. 25:722-729(2012). RN [21] 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 [22] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=23444097; DOI=10.1002/prot.24274; RA Yoval-Sanchez B., Pardo J.P., Rodriguez-Zavala J.S.; RT "New insights into the half-of-the-sites reactivity of human aldehyde RT dehydrogenase 1A1."; RL Proteins 81:1330-1339(2013). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-337 AND SER-413, AND 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 [24] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=25413692; DOI=10.1007/s11095-014-1564-3; RA Jackson B.C., Reigan P., Miller B., Thompson D.C., Vasiliou V.; RT "Human ALDH1B1 polymorphisms may affect the metabolism of acetaldehyde and RT all-trans retinaldehyde--in vitro studies and computational modeling."; RL Pharm. Res. 32:1648-1662(2015). RN [25] RP INTERACTION WITH PRMT3, AND REGION. RX PubMed=33495566; DOI=10.1038/s42003-020-01644-3; RA Verma M., Khan M.I.K., Kadumuri R.V., Chakrapani B., Awasthi S., Mahesh A., RA Govindaraju G., Chavali P.L., Rajavelu A., Chavali S., Dhayalan A.; RT "PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting RT retinoic acid signaling."; RL Commun. Biol. 4:109-109(2021). RN [26] {ECO:0007744|PDB:5AC2} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH DUOCARMYCIN ANALOG, RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF CYS-302. RX PubMed=26373694; DOI=10.1002/anie.201505749; RA Koch M.F., Harteis S., Blank I.D., Pestel G., Tietze L.F., Ochsenfeld C., RA Schneider S., Sieber S.A.; RT "Structural, biochemical, and computational studies reveal the mechanism of RT selective aldehyde dehydrogenase 1A1 inhibition by cytotoxic duocarmycin RT analogues."; RL Angew. Chem. Int. Ed. Engl. 54:13550-13554(2015). RN [27] {ECO:0007744|PDB:4WB9, ECO:0007744|PDB:4WJ9} RP X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF VARIANT SER-121 ALONE AND IN RP COMPLEX WITH NADH, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=25450233; DOI=10.1016/j.cbi.2014.10.028; RA Morgan C.A., Hurley T.D.; RT "Development of a high-throughput in vitro assay to identify selective RT inhibitors for human ALDH1A1."; RL Chem. Biol. Interact. 234:29-37(2015). RN [28] {ECO:0007744|PDB:4WP7, ECO:0007744|PDB:4WPN, ECO:0007744|PDB:4X4L} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH NAD AND INHIBITORS, RP AND MUTAGENESIS OF GLY-458. RX PubMed=25634381; DOI=10.1021/jm501900s; RA Morgan C.A., Hurley T.D.; RT "Characterization of two distinct structural classes of selective aldehyde RT dehydrogenase 1A1 inhibitors."; RL J. Med. Chem. 58:1964-1975(2015). CC -!- FUNCTION: Cytosolic dehydrogenase that catalyzes the NAD(+)-dependent CC irreversible oxidation of a wide range of aldehydes to their CC corresponding carboxylic acid (PubMed:25450233, PubMed:26373694, CC PubMed:22339434, PubMed:23444097). Functions downstream of retinol CC dehydrogenases and catalyzes the oxidation of retinaldehyde into CC retinoic acid, the second step in the oxidation of retinol/vitamin A CC into retinoic acid (PubMed:25413692). This pathway is crucial to CC control the levels of retinol and retinoic acid, two important CC molecules which excess can be teratogenic and cytotoxic CC (PubMed:25413692). Also oxidizes aldehydes resulting from lipid CC peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and CC hexanal that form protein adducts and are highly cytotoxic. By CC participating for instance to the clearance of (E)-4-hydroxynon-2- CC enal/HNE in the lens epithelium prevents the formation of HNE-protein CC adducts and lens opacification (PubMed:12941160, PubMed:15623782, CC PubMed:19296407). Also functions downstream of fructosamine-3-kinase in CC the fructosamine degradation pathway by catalyzing the oxidation of 3- CC deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate CC decomposition, which is itself a potent glycating agent that may react CC with lysine and arginine side-chains of proteins (PubMed:17175089). CC Also has an aminobutyraldehyde dehydrogenase activity and is probably CC part of an alternative pathway for the biosynthesis of GABA/4- CC aminobutanoate in midbrain, thereby playing a role in GABAergic CC synaptic transmission (By similarity). {ECO:0000250|UniProtKB:P24549, CC ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:15623782, CC ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407, CC ECO:0000269|PubMed:22339434, ECO:0000269|PubMed:23444097, CC ECO:0000269|PubMed:25413692, ECO:0000269|PubMed:25450233, CC ECO:0000269|PubMed:26373694}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an aldehyde + NAD(+) + H2O = a carboxylate + NADH + 2 H(+); 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:12941160, CC ECO:0000269|PubMed:15623782, ECO:0000269|PubMed:17175089, CC ECO:0000269|PubMed:19296407, ECO:0000269|PubMed:22339434, CC ECO:0000269|PubMed:23444097}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16186; CC Evidence={ECO:0000305|PubMed:19296407}; CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinal + NAD(+) + H2O = all-trans-retinoate + NADH CC + 2 H(+); Xref=Rhea:RHEA:42080, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17898, ChEBI:CHEBI:35291, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; EC=1.2.1.36; CC Evidence={ECO:0000269|PubMed:25413692}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42081; CC Evidence={ECO:0000305|PubMed:25413692}; CC -!- CATALYTIC ACTIVITY: CC Reaction=9-cis-retinal + NAD(+) + H2O = 9-cis-retinoate + NADH + 2 CC H(+); Xref=Rhea:RHEA:42084, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78273, CC ChEBI:CHEBI:78630; Evidence={ECO:0000250|UniProtKB:P51647}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42085; CC Evidence={ECO:0000250|UniProtKB:P51647}; CC -!- CATALYTIC ACTIVITY: CC Reaction=11-cis-retinal + NAD(+) + H2O = 11-cis-retinoate + NADH + 2 CC H(+); Xref=Rhea:RHEA:47132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16066, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:87435; Evidence={ECO:0000250|UniProtKB:P51647}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47133; CC Evidence={ECO:0000250|UniProtKB:P51647}; CC -!- CATALYTIC ACTIVITY: CC Reaction=13-cis-retinal + NAD(+) + H2O = 13-cis-retinoate + NADH + 2 CC H(+); Xref=Rhea:RHEA:67332, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:45487, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:169952; Evidence={ECO:0000250|UniProtKB:Q8HYE4}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67333; CC Evidence={ECO:0000250|UniProtKB:Q8HYE4}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3-deoxyglucosone + NAD(+) + H2O = 2-dehydro-3-deoxy-D- CC gluconate + NADH + 2 H(+); Xref=Rhea:RHEA:67244, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:57990, ChEBI:CHEBI:60777; CC Evidence={ECO:0000269|PubMed:17175089}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67245; CC Evidence={ECO:0000305|PubMed:17175089}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(E)-4-hydroxynon-2-enal + NAD(+) + H2O = (E)-4-hydroxynon-2- CC enoate + NADH + 2 H(+); Xref=Rhea:RHEA:67248, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:58968, ChEBI:CHEBI:142920; CC Evidence={ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:15623782, CC ECO:0000269|PubMed:19296407, ECO:0000269|PubMed:22339434}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67249; CC Evidence={ECO:0000269|PubMed:15623782}; CC -!- CATALYTIC ACTIVITY: CC Reaction=malonaldehyde + NAD(+) + H2O = 3-oxopropanoate + NADH + 2 CC H(+); Xref=Rhea:RHEA:67252, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:33190, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:566274; Evidence={ECO:0000269|PubMed:12941160, CC ECO:0000269|PubMed:19296407, ECO:0000269|PubMed:22339434}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67253; CC Evidence={ECO:0000305|PubMed:19296407}; CC -!- CATALYTIC ACTIVITY: CC Reaction=hexanal + NAD(+) + H2O = hexanoate + NADH + 2 H(+); 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:12941160}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67277; CC Evidence={ECO:0000305|PubMed:12941160}; CC -!- CATALYTIC ACTIVITY: CC Reaction=propanal + NAD(+) + H2O = propanoate + NADH + 2 H(+); 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:12941160, CC ECO:0000269|PubMed:19296407}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67257; CC Evidence={ECO:0000305|PubMed:19296407}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetaldehyde + NAD(+) + H2O = acetate + NADH + 2 H(+); 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:0000269|PubMed:19296407}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25295; CC Evidence={ECO:0000305|PubMed:19296407}; CC -!- CATALYTIC ACTIVITY: CC Reaction=benzaldehyde + NAD(+) + H2O = benzoate + NADH + 2 H(+); CC Xref=Rhea:RHEA:11840, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16150, ChEBI:CHEBI:17169, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; EC=1.2.1.28; CC Evidence={ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11841; CC Evidence={ECO:0000305|PubMed:19296407}; CC -!- CATALYTIC ACTIVITY: CC Reaction=4-aminobutanal + NAD(+) + H2O = 4-aminobutanoate + NADH + 2 CC H(+); 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:0000250|UniProtKB:P24549}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19106; CC Evidence={ECO:0000250|UniProtKB:P24549}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-glyceraldehyde + NAD(+) + H2O = (R)-glycerate + NADH + 2 CC H(+); Xref=Rhea:RHEA:30783, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16659, ChEBI:CHEBI:17378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:23444097}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30784; CC Evidence={ECO:0000305|PubMed:23444097}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acrolein + NAD(+) + H2O = acrylate + NADH + 2 H(+); 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:22339434}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69085; CC Evidence={ECO:0000305|PubMed:22339434}; CC -!- ACTIVITY REGULATION: Inhibited by citral, disulfiram, and cyanamide. CC Activated by diethylstilbestrol (PubMed:19296407). Inhibited by CC duocarmycin analogs (PubMed:26373694). {ECO:0000269|PubMed:19296407, CC ECO:0000269|PubMed:26373694}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=59.4 uM for NAD(+) (at pH 8.0) {ECO:0000269|PubMed:19296407}; CC KM=85 uM for NAD(+) (at pH 7.1 and 30 degrees Celsius) CC {ECO:0000269|PubMed:17175089}; CC KM=2 uM for benzaldehyde (at pH 7.1 and 30 degrees Celsius) CC {ECO:0000269|PubMed:17175089}; CC KM=4.8 uM for (E)-4-hydroxynon-2-enal (at pH 7.0) CC {ECO:0000269|PubMed:19296407}; CC KM=17.9 uM for (E)-4-hydroxynon-2-enal (at pH 8.0 and 25 degrees CC Celsius) {ECO:0000269|PubMed:12941160}; CC KM=1.7 uM for (E)-4-hydroxynon-2-enal (at pH 7.4) CC {ECO:0000269|PubMed:22339434}; CC KM=1.1 uM for (E)-4-hydroxynon-2-enal (at pH 9.5) CC {ECO:0000269|PubMed:22339434}; CC KM=114.4 uM for malonaldehyde (at pH 8.0 and 25 degrees Celsius) CC {ECO:0000269|PubMed:12941160}; CC KM=3.5 uM for malonaldehyde (at pH 8.0) CC {ECO:0000269|PubMed:19296407}; CC KM=30 uM for malonaldehyde (at pH 7.4) {ECO:0000269|PubMed:22339434}; CC KM=4.3 uM for malonaldehyde (at pH 9.5) CC {ECO:0000269|PubMed:22339434}; CC KM=95 uM for 3-deoxyglucosone (at pH 7.1 and 30 degrees Celsius) CC {ECO:0000269|PubMed:17175089}; CC KM=238.2 uM for acetaldehyde (at pH 8.0) CC {ECO:0000269|PubMed:19296407}; CC KM=121.4 uM for propanal (at pH 8.0) {ECO:0000269|PubMed:19296407}; CC KM=137.2 uM for propanal (at pH 8.0 and 25 degrees Celsius) CC {ECO:0000269|PubMed:12941160}; CC KM=15 uM for propanal (at pH 7.5) {ECO:0000269|PubMed:25450233}; CC KM=13.4 uM for hexanal (at pH 8.0 and 25 degrees Celsius) CC {ECO:0000269|PubMed:12941160}; CC KM=142.2 uM for benzaldehyde (at pH 8.0) CC {ECO:0000269|PubMed:19296407}; CC KM=177.1 uM for trans-2-heptenal (at pH 8.0) CC {ECO:0000269|PubMed:19296407}; CC KM=26.8 uM for all-trans-retinal {ECO:0000269|PubMed:25413692}; CC KM=595 uM for D-glyceraldehyde (at pH 9.5 and 25 degrees Celsius) CC {ECO:0000269|PubMed:23444097}; CC KM=5.4 uM for acrolein (at pH 7.4) {ECO:0000269|PubMed:22339434}; CC KM=9 uM for acrolein (at pH 9.5) {ECO:0000269|PubMed:22339434}; CC Vmax=254.6 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC (E)-4-hydroxynon-2-enal (at pH 8.0 and 25 degrees Celsius) CC {ECO:0000269|PubMed:12941160}; CC Vmax=135 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC (E)-4-hydroxynon-2-enal (at pH 7.0) {ECO:0000269|PubMed:19296407}; CC Vmax=120 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC (E)-4-hydroxynon-2-enal (at pH 7.4) {ECO:0000269|PubMed:22339434}; CC Vmax=441 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC (E)-4-hydroxynon-2-enal (at pH 9.5) {ECO:0000269|PubMed:22339434}; CC Vmax=564.9 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC malonaldehyde (at pH 8.0 and 25 degrees Celsius) CC {ECO:0000269|PubMed:12941160}; CC Vmax=381.6 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC malonaldehyde (at pH 8.0) {ECO:0000269|PubMed:19296407}; CC Vmax=142 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC malonaldehyde (at pH 7.4) {ECO:0000269|PubMed:22339434}; CC Vmax=230 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC malonaldehyde (at pH 9.5) {ECO:0000269|PubMed:22339434}; CC Vmax=45 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC 3-deoxyglucosone (at pH 7.1 and 30 degrees Celsius) CC {ECO:0000269|PubMed:17175089}; CC Vmax=631.4 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC acetaldehyde (at pH 8.0) {ECO:0000269|PubMed:19296407}; CC Vmax=747.3 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC propanal (at pH 8.0 and 25 degrees Celsius) CC {ECO:0000269|PubMed:12941160}; CC Vmax=445.3 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC propanal (at pH 8.0) {ECO:0000269|PubMed:19296407}; CC Vmax=707.1 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC hexanal (at pH 8.0 and 25 degrees Celsius) CC {ECO:0000269|PubMed:12941160}; CC Vmax=750.3 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC benzaldehyde (at pH 8.0) {ECO:0000269|PubMed:19296407}; CC Vmax=72 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC benzaldehyde (at pH 7.1 and 30 degrees Celsius) CC {ECO:0000269|PubMed:17175089}; CC Vmax=155.8 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC trans-2-heptenal (at pH 8.0) {ECO:0000269|PubMed:19296407}; CC Vmax=74.2 nmol/min/mg enzyme with all-trans-retinal CC {ECO:0000269|PubMed:25413692}; CC Vmax=414 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC D-glyceraldehyde (at pH 9.5 and 25 degrees Celsius) CC {ECO:0000269|PubMed:23444097}; CC Vmax=530 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC acrolein (at pH 7.4) {ECO:0000269|PubMed:22339434}; CC Vmax=866 nmol/min/mg enzyme for NAD(+)-dependent oxidation of CC acrolein (at pH 9.5) {ECO:0000269|PubMed:22339434}; CC pH dependence: CC Optimum pH is 7.1-9 for the 3-deoxyglucosone dehydrogenase activity. CC {ECO:0000269|PubMed:17175089}; CC -!- PATHWAY: Cofactor metabolism; retinol metabolism. CC {ECO:0000250|UniProtKB:P51647}. CC -!- SUBUNIT: Homotetramer (By similarity). Interacts with PRMT3; the CC interaction is direct, inhibits ALDH1A1 aldehyde dehydrogenase activity CC and is independent of the methyltransferase activity of PRMT3 CC (PubMed:33495566). {ECO:0000250|UniProtKB:P51977, CC ECO:0000269|PubMed:33495566}. CC -!- INTERACTION: CC P00352; P09172: DBH; NbExp=3; IntAct=EBI-752170, EBI-8589586; CC P00352; P14136: GFAP; NbExp=3; IntAct=EBI-752170, EBI-744302; CC P00352; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-752170, EBI-1055254; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12941160}. CC Cell projection, axon {ECO:0000250|UniProtKB:P24549}. CC -!- TISSUE SPECIFICITY: Expressed by erythrocytes (at protein level). CC {ECO:0000269|PubMed:17175089}. CC -!- PTM: The N-terminus is blocked most probably by acetylation. CC {ECO:0000250|UniProtKB:P15437}. 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; M31994; AAA51692.1; -; Genomic_DNA. DR EMBL; M31982; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31983; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31984; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31985; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31986; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31987; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31988; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31989; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31990; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31991; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; M31992; AAA51692.1; JOINED; Genomic_DNA. DR EMBL; AF003341; AAC51652.1; -; mRNA. DR EMBL; AY390731; AAR92229.1; -; mRNA. DR EMBL; BT006921; AAP35567.1; -; mRNA. DR EMBL; AY338497; AAP88039.1; -; Genomic_DNA. DR EMBL; AL591031; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471089; EAW62543.1; -; Genomic_DNA. DR EMBL; BC001505; AAH01505.1; -; mRNA. DR EMBL; S61235; AAD13925.1; -; Genomic_DNA. DR EMBL; M26761; AAA35518.1; -; mRNA. DR EMBL; K03000; AAA51695.1; -; mRNA. DR CCDS; CCDS6644.1; -. DR PIR; A33371; DEHUE1. DR RefSeq; NP_000680.2; NM_000689.5. DR PDB; 4WB9; X-ray; 2.07 A; A=1-501. DR PDB; 4WJ9; X-ray; 1.74 A; A=1-501. DR PDB; 4WP7; X-ray; 1.80 A; A=1-501. DR PDB; 4WPN; X-ray; 1.95 A; A=1-501. DR PDB; 4X4L; X-ray; 1.85 A; A=1-501. DR PDB; 5AC2; X-ray; 1.85 A; A=1-501. DR PDB; 5L2M; X-ray; 1.70 A; A=1-501. DR PDB; 5L2N; X-ray; 1.70 A; A=1-501. DR PDB; 5L2O; X-ray; 2.05 A; A/B/C/D/E/F/G/H=1-501. DR PDB; 5TEI; X-ray; 2.10 A; A=1-501. DR PDB; 6DUM; X-ray; 2.00 A; A=1-501. DR PDB; 7JWS; X-ray; 1.60 A; A=1-501. DR PDB; 7JWT; X-ray; 1.80 A; A=1-501. DR PDB; 7JWU; X-ray; 1.90 A; A=1-501. DR PDB; 7JWV; X-ray; 1.60 A; A=1-501. DR PDB; 7JWW; X-ray; 1.60 A; A=1-501. DR PDB; 7UM9; X-ray; 1.80 A; A=1-501. DR PDB; 8D46; EM; 2.84 A; A/B/C/D=1-501. DR PDB; 8DNO; EM; 3.40 A; A/B/C/D=1-501. DR PDB; 8ENE; EM; 2.64 A; A/B/C/D=1-501. DR PDB; 8PVH; EM; 2.90 A; A=2-501. DR PDB; 8T0N; X-ray; 1.86 A; A=1-501. DR PDB; 8T0T; X-ray; 1.75 A; A=1-501. DR PDB; 8WFQ; X-ray; 3.50 A; A/B/C/D/E/F/G/H=1-501. DR AlphaFoldDB; P00352; -. DR EMDB; EMD-17966; -. DR EMDB; EMD-27176; -. DR EMDB; EMD-28271; -. DR MDposit; P00352; -. DR MDRepo; P00352; -. DR SMR; P00352; -. DR BioGRID; 106718; 83. DR FunCoup; P00352; 255. DR IntAct; P00352; 45. DR NDEx; IQUERY-CP-ALDH1A1; 7 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000297785; -. DR BindingDB; P00352; -. DR ChEMBL; CHEMBL3577; -. DR DrugBank; DB04447; 1,4-Dithiothreitol. DR DrugBank; DB09116; Calcium carbimide. DR DrugBank; DB09462; Glycerin. DR DrugBank; DB00157; NADH. DR DrugBank; DB00755; Tretinoin. DR DrugBank; DB00162; Vitamin A. DR DrugCentral; P00352; -. DR GlyGen; P00352; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; P00352; -. DR MetOSite; P00352; -. DR PhosphoSitePlus; P00352; -. DR SwissPalm; P00352; -. DR BioMuta; ALDH1A1; -. DR DMDM; 118495; -. DR REPRODUCTION-2DPAGE; IPI00218914; -. DR REPRODUCTION-2DPAGE; P00352; -. DR jPOST; P00352; -. DR MassIVE; P00352; -. DR PaxDb; 9606-ENSP00000297785; -. DR PeptideAtlas; P00352; -. DR ProteomicsDB; 51235; -. DR Pumba; P00352; -. DR Antibodypedia; 1064; 1082 antibodies from 50 providers. DR DNASU; 216; -. DR Ensembl; ENST00000297785.8; ENSP00000297785.3; ENSG00000165092.14. DR Ensembl; ENST00000856200.1; ENSP00000526259.1; ENSG00000165092.14. DR Ensembl; ENST00000856201.1; ENSP00000526260.1; ENSG00000165092.14. DR Ensembl; ENST00000856202.1; ENSP00000526261.1; ENSG00000165092.14. DR Ensembl; ENST00000856203.1; ENSP00000526262.1; ENSG00000165092.14. DR GeneID; 216; -. DR KEGG; hsa:216; -. DR MANE-Select; ENST00000297785.8; ENSP00000297785.3; NM_000689.5; NP_000680.2. DR AGR; HGNC:402; -. DR ClinPGx; PA24692; -. DR CTD; 216; -. DR DisGeNET; 216; -. DR GeneCards; ALDH1A1; -. DR HGNC; HGNC:402; ALDH1A1. DR HPA; ENSG00000165092; Tissue enhanced (liver). DR MIM; 100640; gene. DR OpenTargets; ENSG00000165092; -. DR VEuPathDB; HostDB:ENSG00000165092; -. DR eggNOG; KOG2450; Eukaryota. DR GeneTree; ENSGT00940000154609; -. DR HOGENOM; CLU_005391_0_2_1; -. DR InParanoid; P00352; -. DR OMA; VRHVMIK; -. DR OrthoDB; 310895at2759; -. DR PAN-GO; P00352; 3 GO annotations based on evolutionary models. DR PhylomeDB; P00352; -. DR BioCyc; MetaCyc:HS09183-MONOMER; -. DR BRENDA; 1.2.1.36; 2681. DR PathwayCommons; P00352; -. DR Reactome; R-HSA-5365859; RA biosynthesis pathway. DR Reactome; R-HSA-70350; Fructose catabolism. DR Reactome; R-HSA-71384; Ethanol oxidation. DR Reactome; R-HSA-9927418; Developmental Lineage of Mammary Gland Luminal Epithelial Cells. DR Reactome; R-HSA-9927432; Developmental Lineage of Mammary Gland Myoepithelial Cells. DR Reactome; R-HSA-9938206; Developmental Lineage of Mammary Stem Cells. DR SABIO-RK; P00352; -. DR SignaLink; P00352; -. DR SIGNOR; P00352; -. DR UniPathway; UPA00912; -. DR Agora; ENSG00000165092; -. DR BioGRID-ORCS; 216; 10 hits in 1159 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; ALDH1A1; human. DR EvolutionaryTrace; P00352; -. DR GeneWiki; ALDH1A1; -. DR GenomeRNAi; 216; -. DR Pharos; P00352; Tchem. DR PRO; PR:P00352; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; P00352; protein. DR Bgee; ENSG00000165092; Expressed in bronchial epithelial cell and 201 other cell types or tissues. DR ExpressionAtlas; P00352; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:0106373; F:3-deoxyglucosone dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0140087; F:acetaldehyde dehydrogenase (NAD+) activity; EXP:UniProtKB. DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:UniProtKB. DR GO; GO:0019145; F:aminobutyraldehyde dehydrogenase (NAD+) activity; ISS:UniProtKB. DR GO; GO:0005497; F:androgen binding; TAS:ProtInc. DR GO; GO:0018479; F:benzaldehyde dehydrogenase (NAD+) activity; EXP:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; TAS:UniProtKB. DR GO; GO:0052814; F:medium-chain fatty aldehyde dehydrogenase (NAD+) activity; IEA:RHEA. DR GO; GO:0051287; F:NAD binding; ISS:CAFA. DR GO; GO:0070403; F:NAD+ binding; IDA:UniProtKB. DR GO; GO:0001758; F:retinal dehydrogenase (NAD+) activity; ISS:UniProtKB. DR GO; GO:0042904; P:9-cis-retinoic acid biosynthetic process; IBA:GO_Central. DR GO; GO:0006081; P:aldehyde metabolic process; IBA:GO_Central. DR GO; GO:0110095; P:cellular detoxification of aldehyde; IMP:UniProtKB. DR GO; GO:0030392; P:fructosamine catabolic process; IDA:UniProtKB. DR GO; GO:0006540; P:GABA shunt; ISS:UniProtKB. DR GO; GO:0036438; P:maintenance of lens transparency; ISS:UniProtKB. DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0001523; P:retinoid metabolic process; ISS:UniProtKB. DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway. DR CDD; cd07141; ALDH_F1AB_F2_RALDH1; 1. DR FunFam; 3.40.605.10:FF:000029; Aldehyde dehydrogenase, mitochondrial; 1. DR FunFam; 3.40.605.10:FF:000026; Aldehyde dehydrogenase, putative; 1. DR FunFam; 3.40.309.10:FF:000001; Mitochondrial aldehyde dehydrogenase 2; 1. DR Gene3D; 3.40.605.10; Aldehyde Dehydrogenase, Chain A, domain 1; 1. DR Gene3D; 3.40.309.10; Aldehyde Dehydrogenase, Chain A, domain 2; 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; 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 PDBsum; 4WB9; -. DR PDBsum; 4WJ9; -. DR PDBsum; 4WP7; -. DR PDBsum; 4WPN; -. DR PDBsum; 4X4L; -. DR PDBsum; 5AC2; -. DR PDBsum; 5L2M; -. DR PDBsum; 5L2N; -. DR PDBsum; 5L2O; -. DR PDBsum; 5TEI; -. DR PDBsum; 6DUM; -. DR PDBsum; 7JWS; -. DR PDBsum; 7JWT; -. DR PDBsum; 7JWU; -. DR PDBsum; 7JWV; -. DR PDBsum; 7JWW; -. DR PDBsum; 7UM9; -. DR PDBsum; 8D46; -. DR PDBsum; 8DNO; -. DR PDBsum; 8ENE; -. DR PDBsum; 8PVH; -. DR PDBsum; 8T0N; -. DR PDBsum; 8T0T; -. DR PDBsum; 8WFQ; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell projection; Cytoplasm; KW Direct protein sequencing; Lipid metabolism; NAD; Nucleotide-binding; KW Oxidoreductase; Phosphoprotein; Proteomics identification; KW Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:6723659, FT ECO:0007744|PubMed:22223895" FT CHAIN 2..501 FT /note="Aldehyde dehydrogenase 1A1" FT /id="PRO_0000056415" FT REGION 336..501 FT /note="Mediates interaction with PRMT3" FT /evidence="ECO:0000269|PubMed:33495566" FT ACT_SITE 269 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007, FT ECO:0000255|PROSITE-ProRule:PRU10008, FT ECO:0000269|PubMed:3676276" FT ACT_SITE 303 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007, FT ECO:0000255|PROSITE-ProRule:PRU10008, FT ECO:0000269|PubMed:3676276" FT BINDING 167..170 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25450233, FT ECO:0000269|PubMed:25634381, ECO:0007744|PDB:4WB9, FT ECO:0007744|PDB:4X4L" FT BINDING 193..196 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25450233, FT ECO:0000269|PubMed:25634381, ECO:0007744|PDB:4WB9, FT ECO:0007744|PDB:4X4L" FT BINDING 226..227 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25450233, FT ECO:0000269|PubMed:25634381, ECO:0007744|PDB:4WB9, FT ECO:0007744|PDB:4X4L" FT BINDING 246..247 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25450233, FT ECO:0000269|PubMed:25634381, ECO:0007744|PDB:4WB9, FT ECO:0007744|PDB:4X4L" FT BINDING 269..271 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25450233, FT ECO:0000269|PubMed:25634381, ECO:0007744|PDB:4WB9, FT ECO:0007744|PDB:4X4L" FT BINDING 349..353 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25450233, FT ECO:0000269|PubMed:25634381, ECO:0007744|PDB:4WB9, FT ECO:0007744|PDB:4X4L" FT BINDING 400..402 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:25450233, FT ECO:0000269|PubMed:25634381, ECO:0007744|PDB:4WB9, FT ECO:0007744|PDB:4X4L" FT SITE 170 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250|UniProtKB:P20000" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|PubMed:6723659, FT ECO:0007744|PubMed:22223895" FT MOD_RES 91 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 128 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 252 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 337 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 353 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 367 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 410 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 413 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 419 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 435 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 495 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VARIANT 121 FT /note="N -> S (in dbSNP:rs1049981)" FT /evidence="ECO:0000269|PubMed:8214422" FT /id="VAR_048901" FT VARIANT 125 FT /note="G -> R (in dbSNP:rs11554423)" FT /id="VAR_048902" FT VARIANT 177 FT /note="I -> F (in dbSNP:rs8187929)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_017778" FT MUTAGEN 302 FT /note="C->A,S: Does not prevent inhibition by duocarmycin FT analogs." FT /evidence="ECO:0000269|PubMed:26373694" FT MUTAGEN 458 FT /note="G->N: No significant effect on aldehyde FT dehydrogenase activity. Prevents the inhibition by FT ALDH1A1-specific inhibitors." FT /evidence="ECO:0000269|PubMed:25634381" FT CONFLICT 162 FT /note="V -> I (in Ref. 11; AAA35518 and 12; AAA51695)" FT /evidence="ECO:0000305" FT HELIX 10..13 FT /evidence="ECO:0007829|PDB:8ENE" FT HELIX 15..18 FT /evidence="ECO:0007829|PDB:6DUM" FT STRAND 22..25 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 28..30 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 37..42 FT /evidence="ECO:0007829|PDB:7JWS" FT TURN 43..46 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 47..53 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 57..70 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 76..79 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 82..98 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 100..111 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 115..117 FT /evidence="ECO:0007829|PDB:5L2M" FT HELIX 118..122 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 123..136 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 137..139 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 142..145 FT /evidence="ECO:0007829|PDB:5L2O" FT STRAND 148..159 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 161..166 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 169..171 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 172..185 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 189..193 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 196..198 FT /evidence="ECO:0007829|PDB:8ENE" FT HELIX 200..212 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 218..221 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 226..230 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 231..234 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 241..246 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 248..260 FT /evidence="ECO:0007829|PDB:7JWS" FT TURN 261..263 FT /evidence="ECO:0007829|PDB:8ENE" FT STRAND 265..269 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 275..278 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 280..282 FT /evidence="ECO:0007829|PDB:8WFQ" FT HELIX 284..296 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 297..300 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 308..312 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 313..327 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 348..363 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 367..370 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 373..379 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 385..389 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 392..394 FT /evidence="ECO:0007829|PDB:8D46" FT HELIX 395..398 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 403..412 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 414..422 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 423..425 FT /evidence="ECO:0007829|PDB:8ENE" FT STRAND 428..433 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 437..446 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 450..455 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 462..464 FT /evidence="ECO:0007829|PDB:8D46" FT HELIX 470..472 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 473..475 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 479..483 FT /evidence="ECO:0007829|PDB:7JWS" FT HELIX 484..486 FT /evidence="ECO:0007829|PDB:7JWS" FT STRAND 487..495 FT /evidence="ECO:0007829|PDB:7JWS" SQ SEQUENCE 501 AA; 54862 MW; B26464DC7168348E CRC64; MSSSGTPDLP VLLTDLKIQY TKIFINNEWH DSVSGKKFPV FNPATEEELC QVEEGDKEDV DKAVKAARQA FQIGSPWRTM DASERGRLLY KLADLIERDR LLLATMESMN GGKLYSNAYL NDLAGCIKTL RYCAGWADKI QGRTIPIDGN FFTYTRHEPI GVCGQIIPWN FPLVMLIWKI GPALSCGNTV VVKPAEQTPL TALHVASLIK EAGFPPGVVN IVPGYGPTAG AAISSHMDID KVAFTGSTEV GKLIKEAAGK SNLKRVTLEL GGKSPCIVLA DADLDNAVEF AHHGVFYHQG QCCIAASRIF VEESIYDEFV RRSVERAKKY ILGNPLTPGV TQGPQIDKEQ YDKILDLIES GKKEGAKLEC GGGPWGNKGY FVQPTVFSNV TDEMRIAKEE IFGPVQQIMK FKSLDDVIKR ANNTFYGLSA GVFTKDIDKA ITISSALQAG TVWVNCYGVV SAQCPFGGFK MSGNGRELGE YGFHEYTEVK TVTVKISQKN S //