AL3A1_MOUSE
ID AL3A1_MOUSE Reviewed; 453 AA.
AC P47739; B1ATI7; Q9R203;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Aldehyde dehydrogenase, dimeric NADP-preferring;
DE EC=1.2.1.5 {ECO:0000269|PubMed:25286108};
DE AltName: Full=Aldehyde dehydrogenase 4;
DE AltName: Full=Aldehyde dehydrogenase family 3 member A1;
DE AltName: Full=Dioxin-inducible aldehyde dehydrogenase 3;
GN Name=Aldh3a1; Synonyms=Ahd-4, Ahd4, Aldh3, Aldh4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HeJ;
RX PubMed=8148869; DOI=10.1097/00008571-199312000-00002;
RA Vasiliou V., Reuter S.F., Kozak C.A., Nebert D.W.;
RT "Mouse dioxin-inducible cytosolic aldehyde dehydrogenase-3: AHD4 cDNA
RT sequence, genetic mapping, and differences in mRNA levels.";
RL Pharmacogenetics 3:281-290(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Vasiliou V., Reuter S.F., Nebert D.W.;
RT "Organization and characterization of the murine cytosolic TCDD-inducible
RT aldehyde dehydrogenase gene (ahd4).";
RL Toxicologist 14:410-410(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND VARIANTS
RP ALD3A1C ASN-154; ARG-305 AND VAL-352.
RC STRAIN=DBA/2J, and SWR/J;
RX PubMed=10376761;
RA Shiao T., Tran P., Siegel D., Lee J., Vasiliou V.;
RT "Four amino acid changes are associated with the Aldh3a1 locus polymorphism
RT in mice which may be responsible for corneal sensitivity to ultraviolet
RT light.";
RL Pharmacogenetics 9:145-153(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP FUNCTION.
RC STRAIN=CD-1;
RX PubMed=11784860; DOI=10.1128/mcb.22.3.849-855.2002;
RA Nees D.W., Wawrousek E.F., Robison W.G. Jr., Piatigorsky J.;
RT "Structurally normal corneas in aldehyde dehydrogenase 3a1-deficient
RT mice.";
RL Mol. Cell. Biol. 22:849-855(2002).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=25286108; DOI=10.1042/bj20140624;
RA Kitamura T., Takagi S., Naganuma T., Kihara A.;
RT "Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via
RT two C-terminal tryptophan residues and lipid modification.";
RL Biochem. J. 465:79-87(2015).
CC -!- FUNCTION: ALDHs play a major role in the detoxification of alcohol-
CC derived acetaldehyde (Probable). They are involved in the metabolism of
CC corticosteroids, biogenic amines, neurotransmitters, and lipid
CC peroxidation (Probable). Oxidizes medium and long chain aldehydes into
CC non-toxic fatty acids (PubMed:25286108). Preferentially oxidizes
CC aromatic aldehyde substrates (PubMed:11784860). Comprises about 50
CC percent of corneal epithelial soluble proteins (PubMed:11784860). May
CC play a role in preventing corneal damage caused by ultraviolet light
CC (PubMed:10376761). {ECO:0000250|UniProtKB:P30838,
CC ECO:0000269|PubMed:10376761, ECO:0000269|PubMed:11784860,
CC ECO:0000269|PubMed:25286108, ECO:0000305}.
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=1.2.1.5;
CC Evidence={ECO:0000269|PubMed:25286108};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) + octanal = 2 H(+) + NADH + octanoate;
CC Xref=Rhea:RHEA:44100, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17935, ChEBI:CHEBI:25646, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:25286108};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P30838}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25286108}.
CC -!- TISSUE SPECIFICITY: Constitutively expressed in cornea, stomach, skin,
CC bladder and lungs. Lowest expression levels in lungs and bladder.
CC {ECO:0000269|PubMed:10376761}.
CC -!- POLYMORPHISM: There are two alleles, Ald3a1a and Ald3a1c. Ald3a1c codes
CC for a low activity enzyme and is associated with extensive corneal
CC clouding after exposure to ultraviolet light. Ald3a1a encodes the high
CC activity enzyme. {ECO:0000269|PubMed:10376761}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; U12785; AAA20670.1; -; mRNA.
DR EMBL; AF072815; AAD15964.1; -; mRNA.
DR EMBL; AL646093; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS24808.1; -.
DR RefSeq; NP_001106196.1; NM_001112725.1.
DR RefSeq; NP_031462.2; NM_007436.2.
DR RefSeq; XP_006532089.1; XM_006532026.1.
DR RefSeq; XP_006532090.1; XM_006532027.3.
DR AlphaFoldDB; P47739; -.
DR SMR; P47739; -.
DR BioGRID; 198065; 1.
DR STRING; 10090.ENSMUSP00000019246; -.
DR SwissLipids; SLP:000001745; -.
DR PhosphoSitePlus; P47739; -.
DR jPOST; P47739; -.
DR MaxQB; P47739; -.
DR PaxDb; P47739; -.
DR PeptideAtlas; P47739; -.
DR PRIDE; P47739; -.
DR ProteomicsDB; 296165; -.
DR Antibodypedia; 26030; 484 antibodies from 40 providers.
DR DNASU; 11670; -.
DR Ensembl; ENSMUST00000019246; ENSMUSP00000019246; ENSMUSG00000019102.
DR Ensembl; ENSMUST00000108716; ENSMUSP00000104356; ENSMUSG00000019102.
DR GeneID; 11670; -.
DR KEGG; mmu:11670; -.
DR UCSC; uc007jhd.2; mouse.
DR CTD; 218; -.
DR MGI; MGI:1353451; Aldh3a1.
DR VEuPathDB; HostDB:ENSMUSG00000019102; -.
DR eggNOG; KOG2456; Eukaryota.
DR GeneTree; ENSGT00940000162101; -.
DR HOGENOM; CLU_005391_3_0_1; -.
DR InParanoid; P47739; -.
DR OMA; RHGKRWM; -.
DR OrthoDB; 646662at2759; -.
DR PhylomeDB; P47739; -.
DR TreeFam; TF314264; -.
DR BRENDA; 1.2.1.5; 3474.
DR Reactome; R-MMU-211945; Phase I - Functionalization of compounds.
DR BioGRID-ORCS; 11670; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Aldh3a2; mouse.
DR PRO; PR:P47739; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P47739; protein.
DR Bgee; ENSMUSG00000019102; Expressed in substantia propria of cornea and 82 other tissues.
DR ExpressionAtlas; P47739; baseline and differential.
DR Genevisible; P47739; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; IDA:MGI.
DR GO; GO:0008106; F:alcohol dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:MGI.
DR GO; GO:0018479; F:benzaldehyde dehydrogenase (NAD+) activity; ISO:MGI.
DR GO; GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; IDA:UniProtKB.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051591; P:response to cAMP; ISO:MGI.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
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 InterPro; IPR012394; Aldehyde_DH_NAD(P).
DR PANTHER; PTHR43570; PTHR43570; 1.
DR Pfam; PF00171; Aldedh; 1.
DR PIRSF; PIRSF036492; ALDH; 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 Acetylation; Cytoplasm; Lipid metabolism; NAD; NADP; Oxidoreductase;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P30838"
FT CHAIN 2..453
FT /note="Aldehyde dehydrogenase, dimeric NADP-preferring"
FT /id="PRO_0000056471"
FT ACT_SITE 210
FT /evidence="ECO:0000250"
FT ACT_SITE 244
FT /evidence="ECO:0000250"
FT BINDING 188..193
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P30838"
FT MOD_RES 178
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P30838"
FT MOD_RES 194
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P30838"
FT VARIANT 154
FT /note="I -> N (in allele Ald3a1c)"
FT /evidence="ECO:0000269|PubMed:10376761"
FT VARIANT 305
FT /note="H -> R (in allele Ald3a1c)"
FT /evidence="ECO:0000269|PubMed:10376761"
FT VARIANT 352
FT /note="I -> V (in allele Ald3a1c)"
FT /evidence="ECO:0000269|PubMed:10376761"
FT CONFLICT 88
FT /note="A -> G (in Ref. 1; AAA20670)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="A -> R (in Ref. 3; AAD15964)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 453 AA; 50481 MW; 7B4EA1CC56B5FAA1 CRC64;
MSNISSIVNR ARDAFNSGKT RPLQFRVEQL EALQRMINEN LKGISKALAS NLRKNEWTSY
YEEVAHVLDE IDFTIKGLSD WAEDEPVAKT RQTQEDDLYI HSEPLGVVLV IGAWNYPFNL
TIQPMVGAIA AGNAVVLKPS EVSDHMADLL STLIPQYMDK DLYPVIKGGV PETTELLKEK
FDHIMYTGST AVGKIVMAAA AKHLTPVTLE LGGKSPCYVD KDCDLDVACR RIAWGKFMNS
GQTCVAPDYI LCDPSIQNEI VEKLKKSLKD FYGEDAKQSH DYGRIINDRH FQRVINLIDS
KKVAHGGTWD QPSRYIAPTI LVDVDPQSPV MQEEIFGPVM PIVCVRSLDE AIKFINQREK
PLALYVFSNN DKVIKKMIAE TSSGGVTAND VIVHITVPTL PFGGVGNSGM GAYHGKKSFE
TFSHRRSCLV RSLRNEEANK ARYPPSPAKM PRH
