AL1A1_HORSE
ID AL1A1_HORSE Reviewed; 501 AA.
AC P15437;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2016, sequence version 2.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Aldehyde dehydrogenase 1A1 {ECO:0000250|UniProtKB:P00352};
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:0000250|UniProtKB:P00352};
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;
DE AltName: Full=Aldehyde dehydrogenase, cytosolic {ECO:0000305|PubMed:6723662};
DE AltName: Full=Retinal dehydrogenase 1 {ECO:0000305};
DE Short=RALDH 1 {ECO:0000305};
DE Short=RalDH1 {ECO:0000305};
GN Name=ALDH1A1 {ECO:0000250|UniProtKB:P00352};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP PROTEIN SEQUENCE OF 2-501, AND ACETYLATION AT SER-2.
RX PubMed=6723662; DOI=10.1111/j.1432-1033.1984.tb08152.x;
RA von Bahr-Lindstroem H., Hempel J., Joernvall H.;
RT "The cytoplasmic isoenzyme of horse liver aldehyde dehydrogenase.
RT Relationship to the corresponding human isoenzyme.";
RL Eur. J. Biochem. 141:37-42(1984).
CC -!- FUNCTION: Cytosolic dehydrogenase that catalyzes the irreversible
CC oxidation of a wide range of aldehydes to their corresponding
CC carboxylic acid (By similarity). 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. Functions also downstream
CC of fructosamine-3-kinase in the fructosamine degradation pathway by
CC catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product
CC of fructosamine 3-phosphate decomposition, which is itself a potent
CC glycating agent that may react with lysine and arginine side-chains of
CC proteins (By similarity). Has also an aminobutyraldehyde dehydrogenase
CC activity and is probably part of an alternative pathway for the
CC biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a
CC role in GABAergic synaptic transmission (By similarity).
CC {ECO:0000250|UniProtKB:P00352, ECO:0000250|UniProtKB:P24549}.
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:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16186;
CC Evidence={ECO:0000250|UniProtKB:P00352};
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=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=(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:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67249;
CC Evidence={ECO:0000250|UniProtKB:P00352};
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:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67253;
CC Evidence={ECO:0000250|UniProtKB:P00352};
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:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67277;
CC Evidence={ECO:0000250|UniProtKB:P00352};
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:0000250|UniProtKB:P00352};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67257;
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 -!- 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
CC {ECO:0000250|UniProtKB:P00352}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P24549}.
CC -!- PTM: The N-terminus is blocked most probably by acetylation.
CC {ECO:0000269|PubMed:6723662}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR PIR; S02302; S02302.
DR AlphaFoldDB; P15437; -.
DR SMR; P15437; -.
DR STRING; 9796.ENSECAP00000030248; -.
DR iPTMnet; P15437; -.
DR PaxDb; P15437; -.
DR PeptideAtlas; P15437; -.
DR PRIDE; P15437; -.
DR InParanoid; P15437; -.
DR UniPathway; UPA00912; -.
DR Proteomes; UP000002281; Unplaced.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS: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; ISS:UniProtKB.
DR GO; GO:0019145; F:aminobutyraldehyde dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0018479; F:benzaldehyde dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:RHEA.
DR GO; GO:0051287; F:NAD binding; ISS:CAFA.
DR GO; GO:0001758; F:retinal dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0110095; P:cellular detoxification of aldehyde; ISS: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; Direct protein sequencing;
KW Lipid metabolism; NAD; Oxidoreductase; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT CHAIN 2..501
FT /note="Aldehyde dehydrogenase 1A1"
FT /id="PRO_0000056414"
FT REGION 336..501
FT /note="Mediates interaction with PRMT3"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT ACT_SITE 269
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 303
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 167..170
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 193..196
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 226..227
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 246..247
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 269..271
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 349..353
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT BINDING 400..402
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00352"
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:6723662"
FT MOD_RES 91
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 252
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 337
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 353
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 367
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 410
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 419
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 435
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
FT MOD_RES 495
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00352"
SQ SEQUENCE 501 AA; 54875 MW; 9438E4205E43D109 CRC64;
MSSSGTPDLP VLLTDLKFQY TKIFINNEWH DSVSGKKFPV FNPATEEKLC EVEEGDKEDV
NKAVAAARQA FQIGSPWRTM DASERGRLLY KLADLVERDR LILATMESMN GGKLFSNAYL
MDLGGCLKTL RYCAGWADKI QGRTIPSDGN FFTYTRHEPV GVCGQILPWN FPLLMFLWKI
APALSCGNTV VVKPAEQTPL SALHVATLIK EAGFPPGVVN IVPGYGPTAG AAISSHMDID
KVAFTGSTEV GKLIKEAAGK SNLKRVTLEL GGKSPFIVFA DADLETALEV THQALFYHQG
QCCVAASRLF VEESIYDEFV RRSVERAKKY VLGNPLTPGV SQGPQIDKEQ YDKILDLIES
GKKEGAKLEC GGGPWGNKGY FIQPTVFSNV SDEMRIAKEE IFGPVQQIMK FKSLDDVIKR
ANNTTYGLFA GSFTKDLDKA ITVSAALQAG TVWVNCYGVV SAQCPFGGFK MSGNGREMGE
YGFHEYTEVK TVTVKISQKN S
