AL3A1_RAT
ID AL3A1_RAT Reviewed; 453 AA.
AC P11883;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Aldehyde dehydrogenase, dimeric NADP-preferring;
DE EC=1.2.1.5 {ECO:0000269|PubMed:2831537};
DE AltName: Full=Aldehyde dehydrogenase family 3 member A1;
DE AltName: Full=HTC-ALDH;
DE AltName: Full=Tumor-associated aldehyde dehydrogenase;
GN Name=Aldh3a1; Synonyms=Aldd, Aldh3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=2831537; DOI=10.1073/pnas.85.6.1782;
RA Jones D.E., Brennan M.D., Hempel J., Lindahl R.;
RT "Cloning and complete nucleotide sequence of a full-length cDNA encoding a
RT catalytically functional tumor-associated aldehyde dehydrogenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:1782-1786(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [3]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=2713359; DOI=10.1021/bi00429a034;
RA Hempel J., Harper K., Lindahl R.;
RT "Inducible (class 3) aldehyde dehydrogenase from rat hepatocellular
RT carcinoma and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated liver: distant
RT relationship to the class 1 and 2 enzymes from mammalian liver
RT cytosol/mitochondria.";
RL Biochemistry 28:1160-1167(1989).
RN [4]
RP GENE STRUCTURE.
RX PubMed=8509394; DOI=10.1016/s0021-9258(18)31421-2;
RA Asman D.C., Takimoto K., Pitot H.C., Dunn T.J., Lindahl R.;
RT "Organization and characterization of the rat class 3 aldehyde
RT dehydrogenase gene.";
RL J. Biol. Chem. 268:12530-12536(1993).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=2091023; DOI=10.1002/prot.340080404;
RA Rose J.P., Hempel J., Kuo I., Lindahl R., Wang B.-C.;
RT "Preliminary crystallographic analysis of class 3 rat liver aldehyde
RT dehydrogenase.";
RL Proteins 8:305-308(1990).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
RX PubMed=9095201; DOI=10.1038/nsb0497-317;
RA Liu Z.-J., Sun Y.J., Rose J.P., Chung Y.-J., Hsiao C.D., Chang W.-R.,
RA Kuo I., Perozich J., Lindahl R., Hempel J., Wang B.-C.;
RT "The first structure of an aldehyde dehydrogenase reveals novel
RT interactions between NAD and the Rossmann fold.";
RL Nat. Struct. Biol. 4:317-326(1997).
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:2831537). Preferentially oxidizes
CC aromatic aldehyde substrates (PubMed:2831537). Comprises about 50
CC percent of corneal epithelial soluble proteins (By similarity). May
CC play a role in preventing corneal damage caused by ultraviolet light
CC (By similarity). {ECO:0000250|UniProtKB:P47739,
CC ECO:0000269|PubMed:2831537, 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; Evidence={ECO:0000269|PubMed:2831537};
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:0000250|UniProtKB:P47739};
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P47739}.
CC -!- INDUCTION: This protein can be induced by a number of chemical
CC carcinogens during rat hepatocarcinogenesis.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; J03637; AAA40713.1; -; mRNA.
DR EMBL; BC070924; AAH70924.1; -; mRNA.
DR PIR; A30149; A30149.
DR RefSeq; NP_114178.1; NM_031972.1.
DR PDB; 1AD3; X-ray; 2.60 A; A/B=3-453.
DR PDBsum; 1AD3; -.
DR AlphaFoldDB; P11883; -.
DR SMR; P11883; -.
DR IntAct; P11883; 1.
DR STRING; 10116.ENSRNOP00000003182; -.
DR jPOST; P11883; -.
DR PaxDb; P11883; -.
DR PRIDE; P11883; -.
DR GeneID; 25375; -.
DR KEGG; rno:25375; -.
DR UCSC; RGD:2088; rat.
DR CTD; 218; -.
DR RGD; 2088; Aldh3a1.
DR VEuPathDB; HostDB:ENSRNOG00000002331; -.
DR eggNOG; KOG2456; Eukaryota.
DR HOGENOM; CLU_005391_3_0_1; -.
DR InParanoid; P11883; -.
DR OMA; RHGKRWM; -.
DR OrthoDB; 646662at2759; -.
DR PhylomeDB; P11883; -.
DR TreeFam; TF314264; -.
DR Reactome; R-RNO-211945; Phase I - Functionalization of compounds.
DR SABIO-RK; P11883; -.
DR EvolutionaryTrace; P11883; -.
DR PRO; PR:P11883; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000002331; Expressed in esophagus and 14 other tissues.
DR Genevisible; P11883; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; IDA:RGD.
DR GO; GO:0008106; F:alcohol dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; ISS:UniProtKB.
DR GO; GO:0018479; F:benzaldehyde dehydrogenase (NAD+) activity; ISO:RGD.
DR GO; GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
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; IMP:RGD.
DR GO; GO:0051591; P:response to cAMP; IDA:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; IDA:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
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 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW Lipid metabolism; NAD; NADP; Oxidoreductase; 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_0000056472"
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 HELIX 4..16
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 23..52
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 56..62
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 64..82
FT /evidence="ECO:0007829|PDB:1AD3"
FT TURN 92..95
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 96..104
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 134..138
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 144..157
FT /evidence="ECO:0007829|PDB:1AD3"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 170..176
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 182..188
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 190..201
FT /evidence="ECO:0007829|PDB:1AD3"
FT TURN 202..204
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 216..219
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 225..237
FT /evidence="ECO:0007829|PDB:1AD3"
FT TURN 238..241
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 257..272
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 288..296
FT /evidence="ECO:0007829|PDB:1AD3"
FT TURN 297..300
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 303..305
FT /evidence="ECO:0007829|PDB:1AD3"
FT TURN 311..314
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 329..331
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 337..340
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 348..356
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 362..367
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 371..378
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 384..392
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 393..396
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 416..421
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 423..430
FT /evidence="ECO:0007829|PDB:1AD3"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:1AD3"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:1AD3"
SQ SEQUENCE 453 AA; 50339 MW; 15C501BAB4F9845A CRC64;
MSSISDTVKR AREAFNSGKT RSLQFRIQQL EALQRMINEN LKSISGALAS DLGKNEWTSY
YEEVAHVLEE LDTTIKELPD WAEDEPVAKT RQTQQDDLYI HSEPLGVVLV IGAWNYPFNL
TIQPMVGAVA AGNAVILKPS EVSGHMADLL ATLIPQYMDQ NLYLVVKGGV PETTELLKER
FDHIMYTGST AVGKIVMAAA AKHLTPVTLE LGGKSPCYVD KDCDLDVACR RIAWGKFMNS
GQTCVAPDYI LCDPSIQNQI VEKLKKSLKD FYGEDAKQSR DYGRIINDRH FQRVKGLIDN
QKVAHGGTWD QSSRYIAPTI LVDVDPQSPV MQEEIFGPVM PIVCVRSLEE AIQFINQREK
PLALYVFSNN EKVIKKMIAE TSSGGVTAND VIVHITVPTL PFGGVGNSGM GAYHGKKSFE
TFSHRRSCLV KSLLNEEAHK ARYPPSPAKM PRH
