Full text data of ALDH3A1
ALDH3A1
(ALDH3)
[Confidence: low (only semi-automatic identification from reviews)]
Aldehyde dehydrogenase, dimeric NADP-preferring; 1.2.1.5 (ALDHIII; Aldehyde dehydrogenase 3; Aldehyde dehydrogenase family 3 member A1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Aldehyde dehydrogenase, dimeric NADP-preferring; 1.2.1.5 (ALDHIII; Aldehyde dehydrogenase 3; Aldehyde dehydrogenase family 3 member A1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P30838
ID AL3A1_HUMAN Reviewed; 453 AA.
AC P30838; A8K828; Q9BT37;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-NOV-2010, sequence version 3.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Aldehyde dehydrogenase, dimeric NADP-preferring;
DE EC=1.2.1.5;
DE AltName: Full=ALDHIII;
DE AltName: Full=Aldehyde dehydrogenase 3;
DE AltName: Full=Aldehyde dehydrogenase family 3 member A1;
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], AND VARIANT ALA-134.
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].
RC TISSUE=Stomach;
RX 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].
RC TISSUE=Stomach;
RX 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], AND VARIANT ALA-134.
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 MRNA], AND VARIANT ALA-134.
RC TISSUE=Cervix, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-134.
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-134.
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 [9]
RP PROTEIN SEQUENCE OF 62-453.
RC TISSUE=Stomach;
RX 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 [10]
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-178 AND LYS-194, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEX WITH INHIBITOR,
RP MUTAGENESIS OF CYS-244, AND ACTIVE SITE.
RX PubMed=22021038; DOI=10.1074/jbc.M111.293597;
RA Khanna M., Chen C.H., Kimble-Hill A., Parajuli B., Perez-Miller S.,
RA Baskaran S., Kim J., Dria K., Vasiliou V., Mochly-Rosen D.,
RA Hurley T.D.;
RT "Discovery of a novel class of covalent inhibitor for aldehyde
RT dehydrogenases.";
RL J. Biol. Chem. 286:43486-43494(2011).
RN [15]
RP VARIANT ALA-329.
RX 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 = a
CC carboxylate + 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; AK292193; BAF84882.1; -; mRNA.
DR EMBL; AK314584; BAG37160.1; -; mRNA.
DR EMBL; AC005722; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471212; EAW50909.1; -; Genomic_DNA.
DR EMBL; BC004370; AAH04370.1; -; mRNA.
DR EMBL; BC008892; AAH08892.1; -; mRNA.
DR EMBL; BC021194; AAH21194.1; -; mRNA.
DR PIR; A42584; A42584.
DR RefSeq; NP_000682.3; NM_000691.4.
DR RefSeq; NP_001128639.1; NM_001135167.1.
DR RefSeq; NP_001128640.1; NM_001135168.1.
DR UniGene; Hs.531682; -.
DR PDB; 3SZA; X-ray; 1.48 A; A/B=1-453.
DR PDB; 3SZB; X-ray; 1.51 A; A/B=1-453.
DR PDBsum; 3SZA; -.
DR PDBsum; 3SZB; -.
DR ProteinModelPortal; P30838; -.
DR SMR; P30838; 2-453.
DR IntAct; P30838; 2.
DR STRING; 9606.ENSP00000225740; -.
DR ChEMBL; CHEMBL3578; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P30838; -.
DR DMDM; 311033473; -.
DR PaxDb; P30838; -.
DR PRIDE; P30838; -.
DR DNASU; 218; -.
DR Ensembl; ENST00000225740; ENSP00000225740; ENSG00000108602.
DR Ensembl; ENST00000444455; ENSP00000388469; ENSG00000108602.
DR Ensembl; ENST00000457500; ENSP00000411821; ENSG00000108602.
DR GeneID; 218; -.
DR KEGG; hsa:218; -.
DR UCSC; uc002gwj.3; human.
DR CTD; 218; -.
DR GeneCards; GC17M019641; -.
DR H-InvDB; HIX0013622; -.
DR HGNC; HGNC:405; ALDH3A1.
DR HPA; CAB045957; -.
DR HPA; HPA051150; -.
DR MIM; 100660; gene.
DR neXtProt; NX_P30838; -.
DR PharmGKB; PA24697; -.
DR eggNOG; COG1012; -.
DR HOGENOM; HOG000271515; -.
DR HOVERGEN; HBG050483; -.
DR KO; K00129; -.
DR OMA; QKLPEWA; -.
DR SABIO-RK; P30838; -.
DR ChiTaRS; ALDH3A1; human.
DR EvolutionaryTrace; P30838; -.
DR GeneWiki; Aldehyde_dehydrogenase_3_family,_member_A1; -.
DR GenomeRNAi; 218; -.
DR NextBio; 882; -.
DR PRO; PR:P30838; -.
DR ArrayExpress; P30838; -.
DR Bgee; P30838; -.
DR CleanEx; HS_ALDH3A1; -.
DR Genevestigator; P30838; -.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; IEA:Ensembl.
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:UniProtKB-EC.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
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.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR InterPro; IPR012394; Aldehyde_DH_NAD(P).
DR PANTHER; PTHR11699:SF15; PTHR11699:SF15; 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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; NAD; NADP; Oxidoreductase; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 453 Aldehyde dehydrogenase, dimeric NADP-
FT preferring.
FT /FTId=PRO_0000056470.
FT NP_BIND 188 193 NAD or NADP (By similarity).
FT ACT_SITE 210 210
FT ACT_SITE 244 244
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 178 178 N6-acetyllysine.
FT MOD_RES 194 194 N6-acetyllysine.
FT VARIANT 134 134 S -> A (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 MUTAGEN 244 244 C->S: Abolishes activity.
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. 9; AA sequence).
FT CONFLICT 436 436 D -> E (in Ref. 9; AA sequence).
FT HELIX 3 16
FT TURN 17 20
FT HELIX 23 39
FT HELIX 41 52
FT HELIX 56 61
FT HELIX 64 82
FT HELIX 91 93
FT STRAND 96 104
FT STRAND 106 111
FT STRAND 114 116
FT HELIX 119 130
FT STRAND 134 138
FT HELIX 144 157
FT TURN 160 162
FT HELIX 170 176
FT STRAND 182 188
FT HELIX 190 201
FT TURN 202 204
FT STRAND 207 210
FT STRAND 216 219
FT HELIX 225 237
FT HELIX 238 241
FT STRAND 249 252
FT HELIX 254 256
FT HELIX 257 272
FT HELIX 276 278
FT HELIX 288 298
FT STRAND 301 305
FT TURN 311 314
FT STRAND 319 323
FT HELIX 329 331
FT STRAND 337 344
FT HELIX 348 357
FT STRAND 362 367
FT HELIX 371 380
FT STRAND 384 389
FT HELIX 393 395
FT HELIX 406 408
FT HELIX 416 421
FT STRAND 423 430
FT HELIX 437 442
FT STRAND 443 445
SQ SEQUENCE 453 AA; 50395 MW; D35C488A022FAACA CRC64;
MSKISEAVKR ARAAFSSGRT RPLQFRIQQL EALQRLIQEQ EQELVGALAA DLHKNEWNAY
YEEVVYVLEE IEYMIQKLPE WAADEPVEKT PQTQQDELYI HSEPLGVVLV IGTWNYPFNL
TIQPMVGAIA AGNSVVLKPS 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
//
ID AL3A1_HUMAN Reviewed; 453 AA.
AC P30838; A8K828; Q9BT37;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-NOV-2010, sequence version 3.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Aldehyde dehydrogenase, dimeric NADP-preferring;
DE EC=1.2.1.5;
DE AltName: Full=ALDHIII;
DE AltName: Full=Aldehyde dehydrogenase 3;
DE AltName: Full=Aldehyde dehydrogenase family 3 member A1;
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], AND VARIANT ALA-134.
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].
RC TISSUE=Stomach;
RX 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].
RC TISSUE=Stomach;
RX 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], AND VARIANT ALA-134.
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 MRNA], AND VARIANT ALA-134.
RC TISSUE=Cervix, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-134.
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-134.
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 [9]
RP PROTEIN SEQUENCE OF 62-453.
RC TISSUE=Stomach;
RX 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 [10]
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-178 AND LYS-194, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEX WITH INHIBITOR,
RP MUTAGENESIS OF CYS-244, AND ACTIVE SITE.
RX PubMed=22021038; DOI=10.1074/jbc.M111.293597;
RA Khanna M., Chen C.H., Kimble-Hill A., Parajuli B., Perez-Miller S.,
RA Baskaran S., Kim J., Dria K., Vasiliou V., Mochly-Rosen D.,
RA Hurley T.D.;
RT "Discovery of a novel class of covalent inhibitor for aldehyde
RT dehydrogenases.";
RL J. Biol. Chem. 286:43486-43494(2011).
RN [15]
RP VARIANT ALA-329.
RX 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 = a
CC carboxylate + 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.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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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; AK292193; BAF84882.1; -; mRNA.
DR EMBL; AK314584; BAG37160.1; -; mRNA.
DR EMBL; AC005722; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471212; EAW50909.1; -; Genomic_DNA.
DR EMBL; BC004370; AAH04370.1; -; mRNA.
DR EMBL; BC008892; AAH08892.1; -; mRNA.
DR EMBL; BC021194; AAH21194.1; -; mRNA.
DR PIR; A42584; A42584.
DR RefSeq; NP_000682.3; NM_000691.4.
DR RefSeq; NP_001128639.1; NM_001135167.1.
DR RefSeq; NP_001128640.1; NM_001135168.1.
DR UniGene; Hs.531682; -.
DR PDB; 3SZA; X-ray; 1.48 A; A/B=1-453.
DR PDB; 3SZB; X-ray; 1.51 A; A/B=1-453.
DR PDBsum; 3SZA; -.
DR PDBsum; 3SZB; -.
DR ProteinModelPortal; P30838; -.
DR SMR; P30838; 2-453.
DR IntAct; P30838; 2.
DR STRING; 9606.ENSP00000225740; -.
DR ChEMBL; CHEMBL3578; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P30838; -.
DR DMDM; 311033473; -.
DR PaxDb; P30838; -.
DR PRIDE; P30838; -.
DR DNASU; 218; -.
DR Ensembl; ENST00000225740; ENSP00000225740; ENSG00000108602.
DR Ensembl; ENST00000444455; ENSP00000388469; ENSG00000108602.
DR Ensembl; ENST00000457500; ENSP00000411821; ENSG00000108602.
DR GeneID; 218; -.
DR KEGG; hsa:218; -.
DR UCSC; uc002gwj.3; human.
DR CTD; 218; -.
DR GeneCards; GC17M019641; -.
DR H-InvDB; HIX0013622; -.
DR HGNC; HGNC:405; ALDH3A1.
DR HPA; CAB045957; -.
DR HPA; HPA051150; -.
DR MIM; 100660; gene.
DR neXtProt; NX_P30838; -.
DR PharmGKB; PA24697; -.
DR eggNOG; COG1012; -.
DR HOGENOM; HOG000271515; -.
DR HOVERGEN; HBG050483; -.
DR KO; K00129; -.
DR OMA; QKLPEWA; -.
DR SABIO-RK; P30838; -.
DR ChiTaRS; ALDH3A1; human.
DR EvolutionaryTrace; P30838; -.
DR GeneWiki; Aldehyde_dehydrogenase_3_family,_member_A1; -.
DR GenomeRNAi; 218; -.
DR NextBio; 882; -.
DR PRO; PR:P30838; -.
DR ArrayExpress; P30838; -.
DR Bgee; P30838; -.
DR CleanEx; HS_ALDH3A1; -.
DR Genevestigator; P30838; -.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; IEA:Ensembl.
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:UniProtKB-EC.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
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.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR InterPro; IPR012394; Aldehyde_DH_NAD(P).
DR PANTHER; PTHR11699:SF15; PTHR11699:SF15; 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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; NAD; NADP; Oxidoreductase; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 453 Aldehyde dehydrogenase, dimeric NADP-
FT preferring.
FT /FTId=PRO_0000056470.
FT NP_BIND 188 193 NAD or NADP (By similarity).
FT ACT_SITE 210 210
FT ACT_SITE 244 244
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 178 178 N6-acetyllysine.
FT MOD_RES 194 194 N6-acetyllysine.
FT VARIANT 134 134 S -> A (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 MUTAGEN 244 244 C->S: Abolishes activity.
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. 9; AA sequence).
FT CONFLICT 436 436 D -> E (in Ref. 9; AA sequence).
FT HELIX 3 16
FT TURN 17 20
FT HELIX 23 39
FT HELIX 41 52
FT HELIX 56 61
FT HELIX 64 82
FT HELIX 91 93
FT STRAND 96 104
FT STRAND 106 111
FT STRAND 114 116
FT HELIX 119 130
FT STRAND 134 138
FT HELIX 144 157
FT TURN 160 162
FT HELIX 170 176
FT STRAND 182 188
FT HELIX 190 201
FT TURN 202 204
FT STRAND 207 210
FT STRAND 216 219
FT HELIX 225 237
FT HELIX 238 241
FT STRAND 249 252
FT HELIX 254 256
FT HELIX 257 272
FT HELIX 276 278
FT HELIX 288 298
FT STRAND 301 305
FT TURN 311 314
FT STRAND 319 323
FT HELIX 329 331
FT STRAND 337 344
FT HELIX 348 357
FT STRAND 362 367
FT HELIX 371 380
FT STRAND 384 389
FT HELIX 393 395
FT HELIX 406 408
FT HELIX 416 421
FT STRAND 423 430
FT HELIX 437 442
FT STRAND 443 445
SQ SEQUENCE 453 AA; 50395 MW; D35C488A022FAACA CRC64;
MSKISEAVKR ARAAFSSGRT RPLQFRIQQL EALQRLIQEQ EQELVGALAA DLHKNEWNAY
YEEVVYVLEE IEYMIQKLPE WAADEPVEKT PQTQQDELYI HSEPLGVVLV IGTWNYPFNL
TIQPMVGAIA AGNSVVLKPS 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
//
MIM
100660
*RECORD*
*FIELD* NO
100660
*FIELD* TI
*100660 ALDEHYDE DEHYDROGENASE, FAMILY 3, SUBFAMILY A, MEMBER 1; ALDH3A1
;;ALDEHYDE DEHYDROGENASE 3; ALDH3;;
read moreACETALDEHYDE DEHYDROGENASE 3;;
ALDH, STOMACH TYPE
*FIELD* TX
See 100640. In stomach tissue, Teng (1981) described an isozymic form of
aldehyde dehydrogenase (ALDH). It did not use formaldehyde,
acetaldehyde, or pyruvic aldehyde. Furfuraldehyde and, to a lesser
extent, propionaldehyde were readily oxidized. Teng (1981) found 1
genetic variant among 71 Chinese stomach specimens and a second
different variant among 33 Asiatic Indian specimens. Unlike liver ALDH,
which appears to be a tetramer, the electrophoretic pattern in the
heterozygotes suggested that stomach ALDH is a monomer. ALDH3 is also
present in lung. By study of somatic cell hybrids, Santisteban et al.
(1985) assigned the ALDH3 gene to chromosome 17.
Using PCR with primers based on conserved regions of aldehyde
dehydrogenases, Hsu et al. (1992) isolated ALDH3 clones from a human
stomach cDNA library. The ALDH3 open reading frame encodes a protein of
453 amino acids. The ALDH3 gene consists of 10 exons spanning
approximately 8 kb. Human ALDH3 protein is 81% identical to that of
ALDH3 from rat hepatocarcinoma cells. By analysis of Northern blots and
PCR products, Hsu et al. (1992) found that ALDH3 is transcribed at high
levels in human stomach and in hepatoma cells, but at very low levels in
normal liver. ALDH3 protein expressed in E. coli exhibited kinetic
properties similar to that of ALDH3 purified from human stomach and
liver.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
By in situ hybridization, Hiraoka et al. (1995) mapped the ALDH3 gene to
17p11.2. Rogers et al. (1997) found that ALDH3 is 50 to 85 kb from a
closely related gene, ALDH10 (270200), and stated that the close
linkage, sequence similarity (66% identity between the coding sequences,
excluding the final 35 codons unique to ALDH10), and structural
conservation indicate that the 2 genes share a common origin.
Vasiliou et al. (1999) reviewed eukaryotic aldehyde dehydrogenase genes,
tabulated allelic variants in the human, and recommended nomenclature
based on divergent evolution and chromosomal mapping. They considered
ALDH3 a 'trivial' designation and suggested ALDH3A1 as the official
symbol.
ALDH3 constitutes 20 to 40% of the total water-soluble proteins in
mammalian cornea. Kays and Piatigorsky (1997) showed by Northern blot
analysis that ALDH3 expression in the mouse is at least 500-fold higher
in the cornea than in any other tissue examined, with very low levels of
expression detected in stomach, urinary bladder, ocular lens, and lung.
Histochemical localization showed that this exceptional level of
expression in the mouse cornea occurs in the anterior epithelial cells,
and that little ALDH3 is present in the keratocytes or corneal
endothelial cells. As the anterior-most layer of the cornea, the
epithelium is faced with continual impingement by environmental
stressors, such as UV radiation, that can have deleterious effects on
cellular function. The abundant expression of ALDH3 in the corneal
epithelium is believed to play a role in protecting this vital tissue,
as well as the rest of the eye, from damage generated by UV exposure.
With a demonstrated substrate preference for the medium-length aliphatic
aldehyde products of UV-induced lipid peroxidation, ALDH3 is thought to
be responsible for preventing the accumulation of these toxic products
in the cornea. In addition to its detoxification function, ALDH3 may
protect the eye by the direct absorption of UV radiation. The high
UV-absorbing capacity of ALDH3, which is attributed both to its high
tryptophan content and to its ability to bind NAD, led some
investigators to term this major corneal protein 'absorbin.'
Kays and Piatigorsky (1997) showed that a promoter fragment derived from
the mouse ALDH3 gene is capable of targeting expression of the
chloramphenicol acetyltransferease (cat) reporter gene specifically to
the epithelial layer of the cornea in transgenic mice, mimicking the
expression pattern of the endogenous ALDH3 gene. Together with other
results, the experiments indicated that tissue-specific expression of
ALDH3 is determined by positive and negative elements in the 5-prime
flanking region of the gene and suggested putative silencers located in
intron 1.
*FIELD* RF
1. Hiraoka, L. R.; Hsu, L.; Hsieh, C.-L.: Assignment of ALDH3 to
human chromosome 17p11.2 and ALDH5 to human chromosome 9p13. Genomics 25:
323-325, 1995.
2. Hsu, L. C.; Chang, W.-C.; Shibuya, A.; Yoshida, A.: Human stomach
aldehyde dehydrogenase cDNA and genomic cloning, primary structure,
and expression in Escherichia coli. J. Biol. Chem. 267: 3030-3037,
1992.
3. Kays, W. T.; Piatigorsky, J.: Aldehyde dehydrogenase class 3 expression:
identification of a cornea-preferred gene promoter in transgenic mice. Proc.
Nat. Acad. Sci. 94: 13594-13599, 1997.
4. Rogers, G. R.; Markova, N. G.; De Laurenzi, V.; Rizzo, W. B.; Compton,
J. G.: Genomic organization and expression of the human fatty aldehyde
dehydrogenase gene (FALDH). Genomics 39: 127-135, 1997.
5. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World Distribution.
New York: Oxford Univ. Press (pub.) 1988.
6. Santisteban, I.; Povey, S.; West, L. F.; Parrington, J. M.; Hopkinson,
D. A.: Chromosome assignment, biochemical and immunological studies
on a human aldehyde dehydrogenase, ALDH3. Ann. Hum. Genet. 49: 87-100,
1985.
7. Teng, Y.-S.: Stomach aldehyde dehydrogenase: report of a new locus. Hum.
Hered. 31: 74-77, 1981.
8. Vasiliou, V.; Bairoch, A.; Tipton, K. F.; Nebert, D. W.: Eukaryotic
aldehyde dehydrogenase (ALDH) genes: human polymorphisms, and recommended
nomenclature based on divergent evolution and chromosomal mapping. Pharmacogenetics 9:
421-434, 1999.
*FIELD* CN
Victor A. McKusick - updated: 6/12/2000
Victor A. McKusick - updated: 11/4/1999
Rebekah S. Rasooly - updated: 2/10/1998
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 04/03/2001
terry: 6/12/2000
carol: 11/9/1999
terry: 11/4/1999
dkim: 7/17/1998
dkim: 6/30/1998
carol: 6/16/1998
alopez: 2/10/1998
mimman: 9/24/1997
jenny: 7/2/1997
jenny: 7/1/1997
alopez: 6/3/1997
terry: 2/7/1995
mimadm: 2/11/1994
supermim: 3/16/1992
carol: 12/6/1990
supermim: 3/20/1990
ddp: 10/26/1989
*RECORD*
*FIELD* NO
100660
*FIELD* TI
*100660 ALDEHYDE DEHYDROGENASE, FAMILY 3, SUBFAMILY A, MEMBER 1; ALDH3A1
;;ALDEHYDE DEHYDROGENASE 3; ALDH3;;
read moreACETALDEHYDE DEHYDROGENASE 3;;
ALDH, STOMACH TYPE
*FIELD* TX
See 100640. In stomach tissue, Teng (1981) described an isozymic form of
aldehyde dehydrogenase (ALDH). It did not use formaldehyde,
acetaldehyde, or pyruvic aldehyde. Furfuraldehyde and, to a lesser
extent, propionaldehyde were readily oxidized. Teng (1981) found 1
genetic variant among 71 Chinese stomach specimens and a second
different variant among 33 Asiatic Indian specimens. Unlike liver ALDH,
which appears to be a tetramer, the electrophoretic pattern in the
heterozygotes suggested that stomach ALDH is a monomer. ALDH3 is also
present in lung. By study of somatic cell hybrids, Santisteban et al.
(1985) assigned the ALDH3 gene to chromosome 17.
Using PCR with primers based on conserved regions of aldehyde
dehydrogenases, Hsu et al. (1992) isolated ALDH3 clones from a human
stomach cDNA library. The ALDH3 open reading frame encodes a protein of
453 amino acids. The ALDH3 gene consists of 10 exons spanning
approximately 8 kb. Human ALDH3 protein is 81% identical to that of
ALDH3 from rat hepatocarcinoma cells. By analysis of Northern blots and
PCR products, Hsu et al. (1992) found that ALDH3 is transcribed at high
levels in human stomach and in hepatoma cells, but at very low levels in
normal liver. ALDH3 protein expressed in E. coli exhibited kinetic
properties similar to that of ALDH3 purified from human stomach and
liver.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
By in situ hybridization, Hiraoka et al. (1995) mapped the ALDH3 gene to
17p11.2. Rogers et al. (1997) found that ALDH3 is 50 to 85 kb from a
closely related gene, ALDH10 (270200), and stated that the close
linkage, sequence similarity (66% identity between the coding sequences,
excluding the final 35 codons unique to ALDH10), and structural
conservation indicate that the 2 genes share a common origin.
Vasiliou et al. (1999) reviewed eukaryotic aldehyde dehydrogenase genes,
tabulated allelic variants in the human, and recommended nomenclature
based on divergent evolution and chromosomal mapping. They considered
ALDH3 a 'trivial' designation and suggested ALDH3A1 as the official
symbol.
ALDH3 constitutes 20 to 40% of the total water-soluble proteins in
mammalian cornea. Kays and Piatigorsky (1997) showed by Northern blot
analysis that ALDH3 expression in the mouse is at least 500-fold higher
in the cornea than in any other tissue examined, with very low levels of
expression detected in stomach, urinary bladder, ocular lens, and lung.
Histochemical localization showed that this exceptional level of
expression in the mouse cornea occurs in the anterior epithelial cells,
and that little ALDH3 is present in the keratocytes or corneal
endothelial cells. As the anterior-most layer of the cornea, the
epithelium is faced with continual impingement by environmental
stressors, such as UV radiation, that can have deleterious effects on
cellular function. The abundant expression of ALDH3 in the corneal
epithelium is believed to play a role in protecting this vital tissue,
as well as the rest of the eye, from damage generated by UV exposure.
With a demonstrated substrate preference for the medium-length aliphatic
aldehyde products of UV-induced lipid peroxidation, ALDH3 is thought to
be responsible for preventing the accumulation of these toxic products
in the cornea. In addition to its detoxification function, ALDH3 may
protect the eye by the direct absorption of UV radiation. The high
UV-absorbing capacity of ALDH3, which is attributed both to its high
tryptophan content and to its ability to bind NAD, led some
investigators to term this major corneal protein 'absorbin.'
Kays and Piatigorsky (1997) showed that a promoter fragment derived from
the mouse ALDH3 gene is capable of targeting expression of the
chloramphenicol acetyltransferease (cat) reporter gene specifically to
the epithelial layer of the cornea in transgenic mice, mimicking the
expression pattern of the endogenous ALDH3 gene. Together with other
results, the experiments indicated that tissue-specific expression of
ALDH3 is determined by positive and negative elements in the 5-prime
flanking region of the gene and suggested putative silencers located in
intron 1.
*FIELD* RF
1. Hiraoka, L. R.; Hsu, L.; Hsieh, C.-L.: Assignment of ALDH3 to
human chromosome 17p11.2 and ALDH5 to human chromosome 9p13. Genomics 25:
323-325, 1995.
2. Hsu, L. C.; Chang, W.-C.; Shibuya, A.; Yoshida, A.: Human stomach
aldehyde dehydrogenase cDNA and genomic cloning, primary structure,
and expression in Escherichia coli. J. Biol. Chem. 267: 3030-3037,
1992.
3. Kays, W. T.; Piatigorsky, J.: Aldehyde dehydrogenase class 3 expression:
identification of a cornea-preferred gene promoter in transgenic mice. Proc.
Nat. Acad. Sci. 94: 13594-13599, 1997.
4. Rogers, G. R.; Markova, N. G.; De Laurenzi, V.; Rizzo, W. B.; Compton,
J. G.: Genomic organization and expression of the human fatty aldehyde
dehydrogenase gene (FALDH). Genomics 39: 127-135, 1997.
5. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World Distribution.
New York: Oxford Univ. Press (pub.) 1988.
6. Santisteban, I.; Povey, S.; West, L. F.; Parrington, J. M.; Hopkinson,
D. A.: Chromosome assignment, biochemical and immunological studies
on a human aldehyde dehydrogenase, ALDH3. Ann. Hum. Genet. 49: 87-100,
1985.
7. Teng, Y.-S.: Stomach aldehyde dehydrogenase: report of a new locus. Hum.
Hered. 31: 74-77, 1981.
8. Vasiliou, V.; Bairoch, A.; Tipton, K. F.; Nebert, D. W.: Eukaryotic
aldehyde dehydrogenase (ALDH) genes: human polymorphisms, and recommended
nomenclature based on divergent evolution and chromosomal mapping. Pharmacogenetics 9:
421-434, 1999.
*FIELD* CN
Victor A. McKusick - updated: 6/12/2000
Victor A. McKusick - updated: 11/4/1999
Rebekah S. Rasooly - updated: 2/10/1998
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 04/03/2001
terry: 6/12/2000
carol: 11/9/1999
terry: 11/4/1999
dkim: 7/17/1998
dkim: 6/30/1998
carol: 6/16/1998
alopez: 2/10/1998
mimman: 9/24/1997
jenny: 7/2/1997
jenny: 7/1/1997
alopez: 6/3/1997
terry: 2/7/1995
mimadm: 2/11/1994
supermim: 3/16/1992
carol: 12/6/1990
supermim: 3/20/1990
ddp: 10/26/1989