AL1A1_RABIT
ID AL1A1_RABIT Reviewed; 496 AA.
AC Q8MI17;
DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Aldehyde dehydrogenase 1A1 {ECO:0000305|PubMed:12941160};
DE EC=1.2.1.19 {ECO:0000250|UniProtKB:P24549};
DE EC=1.2.1.28 {ECO:0000250|UniProtKB:P00352};
DE EC=1.2.1.3 {ECO:0000269|PubMed:12941160};
DE EC=1.2.1.36 {ECO:0000250|UniProtKB:P51647};
DE AltName: Full=3-deoxyglucosone dehydrogenase {ECO:0000250|UniProtKB:P00352};
DE AltName: Full=ALDH-E1;
DE AltName: Full=ALHDII;
DE AltName: Full=Aldehyde dehydrogenase family 1 member A1 {ECO:0000303|PubMed:12941160};
DE AltName: Full=Aldehyde dehydrogenase, cytosolic {ECO:0000305};
DE AltName: Full=Retinal dehydrogenase 1 {ECO:0000305};
DE Short=RALDH 1 {ECO:0000305};
DE Short=RalDH1 {ECO:0000305};
GN Name=ALDH1A1 {ECO:0000303|PubMed:12941160};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RC TISSUE=Cornea;
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).
CC -!- FUNCTION: Cytosolic dehydrogenase that catalyzes the irreversible
CC oxidation of a wide range of aldehydes to their corresponding
CC carboxylic acid (PubMed:12941160). 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. This pathway is crucial to control the levels of
CC retinol and retinoic acid, two important molecules which excess can be
CC teratogenic and cytotoxic (By similarity). Also oxidizes aldehydes
CC resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE,
CC malonaldehyde and hexanal that form protein adducts and are highly
CC cytotoxic. By participating for instance to the clearance of (E)-4-
CC hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of
CC HNE-protein adducts and lens opacification (PubMed:12941160). Functions
CC also downstream of fructosamine-3-kinase in the fructosamine
CC degradation pathway by catalyzing the oxidation of 3-deoxyglucosone,
CC the carbohydrate product of fructosamine 3-phosphate decomposition,
CC which is itself a potent glycating agent that may react with lysine and
CC arginine side-chains of proteins (By similarity). Has also an
CC aminobutyraldehyde dehydrogenase activity and is probably part of an
CC alternative pathway for the biosynthesis of GABA/4-aminobutanoate in
CC midbrain, thereby playing a role in GABAergic synaptic transmission (By
CC similarity). {ECO:0000250|UniProtKB:P00352,
CC ECO:0000250|UniProtKB:P24549, ECO:0000269|PubMed:12941160}.
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;
CC Evidence={ECO:0000269|PubMed:12941160};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16186;
CC Evidence={ECO:0000305|PubMed:12941160};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinal + H2O + NAD(+) = all-trans-retinoate + 2
CC H(+) + NADH; Xref=Rhea:RHEA:42080, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17898, ChEBI:CHEBI:35291,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.36;
CC Evidence={ECO:0000250|UniProtKB:P51647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42081;
CC Evidence={ECO:0000250|UniProtKB:P51647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-cis-retinal + H2O + NAD(+) = 9-cis-retinoate + 2 H(+) +
CC NADH; 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 + H2O + NAD(+) = 11-cis-retinoate + 2 H(+) +
CC NADH; 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 + H2O + NAD(+) = 13-cis-retinoate + 2 H(+) +
CC NADH; 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=(E)-4-hydroxynon-2-enal + H2O + NAD(+) = (E)-4-hydroxynon-2-
CC enoate + 2 H(+) + NADH; 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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67249;
CC Evidence={ECO:0000305|PubMed:12941160};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + malonaldehyde + NAD(+) = 3-oxopropanoate + 2 H(+) +
CC NADH; 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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67253;
CC Evidence={ECO:0000305|PubMed:12941160};
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:12941160};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67277;
CC Evidence={ECO:0000305|PubMed:12941160};
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:12941160};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67257;
CC Evidence={ECO:0000305|PubMed:12941160};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-deoxyglucosone + H2O + NAD(+) = 2-dehydro-3-deoxy-D-
CC gluconate + 2 H(+) + NADH; 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:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67245;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetaldehyde + H2O + NAD(+) = acetate + 2 H(+) + NADH;
CC Xref=Rhea:RHEA:25294, ChEBI:CHEBI:15343, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.3;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25295;
CC Evidence={ECO:0000250|UniProtKB:P00352};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=benzaldehyde + H2O + NAD(+) = benzoate + 2 H(+) + NADH;
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:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11841;
CC Evidence={ECO:0000250|UniProtKB:P00352};
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:0000250|UniProtKB:P24549};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19106;
CC Evidence={ECO:0000250|UniProtKB:P24549};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.1 uM for (E)-4-hydroxynon-2-enal {ECO:0000269|PubMed:12941160};
CC KM=14 uM for malonaldehyde {ECO:0000269|PubMed:12941160};
CC KM=3.5 uM for hexanal {ECO:0000269|PubMed:12941160};
CC KM=66.2 uM for propanal {ECO:0000269|PubMed:12941160};
CC Vmax=112.9 nmol/min/mg enzyme with (E)-4-hydroxynon-2-enal
CC {ECO:0000269|PubMed:12941160};
CC Vmax=303.9 nmol/min/mg enzyme with malonaldehyde
CC {ECO:0000269|PubMed:12941160};
CC Vmax=146.9 nmol/min/mg enzyme with hexanal
CC {ECO:0000269|PubMed:12941160};
CC Vmax=523 nmol/min/mg enzyme with propanal
CC {ECO:0000269|PubMed:12941160};
CC Note=Has a lower activity toward propanal.
CC {ECO:0000269|PubMed:12941160};
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 (By
CC similarity). {ECO:0000250|UniProtKB:P00352,
CC ECO:0000250|UniProtKB:P51977}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12941160}.
CC Cell projection, axon {ECO:0000250|UniProtKB:P24549}.
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; AY038801; AAK72097.1; -; mRNA.
DR AlphaFoldDB; Q8MI17; -.
DR SMR; Q8MI17; -.
DR STRING; 9986.ENSOCUP00000018475; -.
DR eggNOG; KOG2450; Eukaryota.
DR InParanoid; Q8MI17; -.
DR SABIO-RK; Q8MI17; -.
DR UniPathway; UPA00912; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0106373; F:3-deoxyglucosone dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0019145; F:aminobutyraldehyde dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0018479; F:benzaldehyde dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:RHEA.
DR GO; GO:0001758; F:retinal dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0110095; P:cellular detoxification of aldehyde; IC:UniProtKB.
DR GO; GO:0030392; P:fructosamine catabolic process; ISS:UniProtKB.
DR GO; GO:0009449; P:gamma-aminobutyric acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0036438; P:maintenance of lens transparency; ISS:UniProtKB.
DR GO; GO:0001523; P:retinoid metabolic process; ISS:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
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 Acetylation; Cell projection; Cytoplasm; Lipid metabolism; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..496
FT /note="Aldehyde dehydrogenase 1A1"
FT /id="PRO_0000056418"
FT REGION 331..496
FT /note="Mediates interaction with PRMT3"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT ACT_SITE 264
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 298
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 162..165
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 188..191
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 221..222
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 241..242
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 264..266
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 344..348
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 395..397
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT SITE 165
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT MOD_RES 86
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 123
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 247
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 348
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 362
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 405
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 414
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 430
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 490
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
SQ SEQUENCE 496 AA; 54341 MW; 4BD963CF015FD164 CRC64;
MADLPTPLTN LKIQYTKIFI NNEWHDSVSG KKFPVLNPAT EEQICLIEEG DKADVDKAVK
AARQAFQIGS PWRTMDASER GRLLYKLADL IERDRLLLAT MESLNAGKLF PNAYLMDLGG
CIKTLRYCAG WADKIQGRTM PMDGDFFCYT RHEPVGVCGQ IIPWNFPLVM LIWKIGPALS
CGNTVIVKPA EQTPLTALHV ASLIKEAGFP PGVVNIVPGY GPTAGAAISS HMDIDKVAFT
GSTEVGKLIK EAAGKSNLKR VTLELGGKSP CIVFADADLD NAVEFAHQGV FYHQGQCCIA
ASRLFVEESI YDEFVRRSVE RAKKYVLGNP LAPEVNQGPQ IDKEQYNKIL DLIESGKKEG
AKLECGGGPW GNKGYFIQPT VFSNVTDEMR IAKEEIFGPV QQIMKFKSLD DVIKRANNTT
YGLSAGIFTK DLDKAVTVSS ALQAGTVWVN CYSVVSAQVP FGGFKMSGNG RELGEYGLQQ
YTEVKTVTVK ISQKNS
