ID   AL3A1_HUMAN             Reviewed;         453 AA.
AC   P30838; Q9BT37;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2004, sequence version 2.
DT   07-JUL-2009, entry version 97.
DE   RecName: Full=Aldehyde dehydrogenase, dimeric NADP-preferring;
DE            EC=1.2.1.5;
DE   AltName: Full=Aldehyde dehydrogenase family 3 member A1;
DE            Short=Aldehyde dehydrogenase 3;
DE   AltName: Full=ALDHIII;
GN   Name=ALDH3A1; Synonyms=ALDH3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Stomach;
RA   Schuuring E.M.D., Verhoeven E., Eckey R., Vos H.L., Michalides R.J.A.;
RT   "Cloning and complete nucleotide sequence of a cDNA encoding the full-
RT   length open reading frame of the human aldehyde dehydrogenase type III
RT   gene.";
RL   Submitted (AUG-1991) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-134.
RC   TISSUE=Stomach;
RX   MEDLINE=92147646; PubMed=1737758;
RA   Hsu L.C., Chang W.-C., Shibuya A., Yoshida A.;
RT   "Human stomach aldehyde dehydrogenase cDNA and genomic cloning,
RT   primary structure, and expression in Escherichia coli.";
RL   J. Biol. Chem. 267:3030-3037(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-134.
RC   TISSUE=Stomach;
RX   MEDLINE=93263008; PubMed=8493892;
RA   Hsu L.C., Yoshida A.;
RT   "Human stomach aldehyde dehydrogenase, ALDH3.";
RL   Adv. Exp. Med. Biol. 328:141-152(1993).
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
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-134.
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA   Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA   Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA   Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA   Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA   Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA   Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA   Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT   the human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   PARTIAL PROTEIN SEQUENCE OF 62-453.
RC   TISSUE=Stomach;
RX   MEDLINE=91243885; PubMed=2037078; DOI=10.1016/0014-5793(91)80559-L;
RA   Yin S.-J., Vagelopoulos N., Wang S.-L., Joernvall H.;
RT   "Structural features of stomach aldehyde dehydrogenase distinguish
RT   dimeric aldehyde dehydrogenase as a 'variable' enzyme. 'Variable' and
RT   'constant' enzymes within the alcohol and aldehyde dehydrogenase
RT   families.";
RL   FEBS Lett. 283:85-88(1991).
RN   [8]
RP   CHARACTERIZATION.
RX   PubMed=1905102;
RA   Eckey R., Timmann R., Hempel J., Agarwal D.P., Goedde H.W.;
RT   "Biochemical, immunological, and molecular characterization of a 'high
RT   Km' aldehyde dehydrogenase.";
RL   Adv. Exp. Med. Biol. 284:43-52(1991).
RN   [9]
RP   VARIANT ALA-329.
RX   MEDLINE=97393928; PubMed=9250352; DOI=10.1017/S0003480097006143;
RA   Tsukamoto N., Chang C., Yoshida A.;
RT   "Mutations associated with Sjogren-Larsson syndrome.";
RL   Ann. Hum. Genet. 61:235-242(1997).
CC   -!- FUNCTION: ALDHs play a major role in the detoxification of
CC       alcohol-derived acetaldehyde. They are involved in the metabolism
CC       of corticosteroids, biogenic amines, neurotransmitters, and lipid
CC       peroxidation. This protein preferentially oxidizes aromatic
CC       aldehyde substrates. It may play a role in the oxidation of toxic
CC       aldehydes.
CC   -!- CATALYTIC ACTIVITY: An aldehyde + NAD(P)(+) + H(2)O = an acid +
CC       NAD(P)H.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         Note=Has a high Km for acetaldehyde;
CC   -!- SUBUNIT: Homodimer.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- TISSUE SPECIFICITY: High levels in stomach, esophagus and lung;
CC       low level in the liver and kidney.
CC   -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
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DR   EMBL; M74542; AAA51696.1; -; mRNA.
DR   EMBL; M77477; AAB46377.1; -; mRNA.
DR   EMBL; S61044; AAB26658.1; -; mRNA.
DR   EMBL; BT007102; AAP35766.1; -; mRNA.
DR   EMBL; AC005722; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC004370; AAH04370.1; -; mRNA.
DR   EMBL; BC008892; AAH08892.1; -; mRNA.
DR   EMBL; BC021194; AAH21194.1; -; mRNA.
DR   IPI; IPI00296183; -.
DR   PIR; A42584; A42584.
DR   RefSeq; NP_001128639.1; -.
DR   UniGene; Hs.531682; -.
DR   HSSP; P11883; 1AD3.
DR   SMR; P30838; 4-448.
DR   PhosphoSite; P30838; -.
DR   Cornea-2DPAGE; P30838; -.
DR   PRIDE; P30838; -.
DR   Ensembl; ENSG00000108602; Homo sapiens.
DR   GeneID; 218; -.
DR   GeneCards; GC17M019581; -.
DR   H-InvDB; HIX0013622; -.
DR   HGNC; HGNC:405; ALDH3A1.
DR   MIM; 100660; gene.
DR   PharmGKB; PA24697; -.
DR   HOVERGEN; P30838; -.
DR   BRENDA; 1.2.1.5; 247.
DR   DrugBank; DB00157; NADH.
DR   NextBio; 882; -.
DR   ArrayExpress; P30838; -.
DR   Bgee; P30838; -.
DR   CleanEx; HS_ALDH3A1; -.
DR   GermOnline; ENSG00000108602; Homo sapiens.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR   GO; GO:0008106; F:alcohol dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR   GO; GO:0004029; F:aldehyde dehydrogenase (NAD) activity; IDA:UniProtKB.
DR   GO; GO:0004030; F:aldehyde dehydrogenase [NAD(P)+] activity; IEA:EC.
DR   GO; GO:0006081; P:cellular aldehyde metabolic process; IDA:UniProtKB.
DR   GO; GO:0055114; P:oxidation reduction; IDA:UniProtKB.
DR   InterPro; IPR016160; Ald_DH_CS.
DR   InterPro; IPR016162; Ald_DH_N.
DR   InterPro; IPR015590; Aldehyde_DH.
DR   InterPro; IPR012394; Aldehyde_DH_NAD(P).
DR   Gene3D; G3DSA:3.40.605.10; Aldehyde_dehydrogenase_N; 1.
DR   PANTHER; PTHR11699; Aldehyde_dehyd; 1.
DR   PANTHER; PTHR11699:SF15; ALDH; 1.
DR   Pfam; PF00171; Aldedh; 1.
DR   PIRSF; PIRSF036492; ALDH; 1.
DR   PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR   PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Cytoplasm; Direct protein sequencing; NADP;
KW   Oxidoreductase; Polymorphism.
FT   CHAIN         1    453       Aldehyde dehydrogenase, dimeric NADP-
FT                                preferring.
FT                                /FTId=PRO_0000056470.
FT   NP_BIND     188    193       NAD (By similarity).
FT   ACT_SITE    210    210       By similarity.
FT   ACT_SITE    244    244       By similarity.
FT   VARIANT     134    134       A -> S (in dbSNP:rs887241).
FT                                /FTId=VAR_018981.
FT   VARIANT     309    309       G -> E (in dbSNP:rs3744692).
FT                                /FTId=VAR_018982.
FT   VARIANT     329    329       P -> A (in allele ALDH3A1*2;
FT                                dbSNP:rs2228100).
FT                                /FTId=VAR_011303.
FT   CONFLICT     12     12       R -> P (in Ref. 2; AAB46377 and 3;
FT                                AAB26658).
FT   CONFLICT     27     27       I -> F (in Ref. 1; AAA51696).
FT   CONFLICT    170    170       V -> L (in Ref. 7; AA sequence).
FT   CONFLICT    436    436       D -> E (in Ref. 7; AA sequence).
SQ   SEQUENCE   453 AA;  50379 MW;  8F3DAEE33775A47A CRC64;
     MSKISEAVKR ARAAFSSGRT RPLQFRIQQL EALQRLIQEQ EQELVGALAA DLHKNEWNAY
     YEEVVYVLEE IEYMIQKLPE WAADEPVEKT PQTQQDELYI HSEPLGVVLV IGTWNYPFNL
     TIQPMVGAIA AGNAVVLKPS ELSENMASLL ATIIPQYLDK DLYPVINGGV PETTELLKER
     FDHILYTGST GVGKIIMTAA AKHLTPVTLE LGGKSPCYVD KNCDLDVACR RIAWGKFMNS
     GQTCVAPDYI LCDPSIQNQI VEKLKKSLKE FYGEDAKKSR DYGRIISARH FQRVMGLIEG
     QKVAYGGTGD AATRYIAPTI LTDVDPQSPV MQEEIFGPVL PIVCVRSLEE AIQFINQREK
     PLALYMFSSN DKVIKKMIAE TSSGGVAAND VIVHITLHSL PFGGVGNSGM GSYHGKKSFE
     TFSHRRSCLV RPLMNDEGLK VRYPPSPAKM TQH
//