Full text data of ALDH9A1
ALDH9A1
(ALDH4, ALDH7, ALDH9)
[Confidence: low (only semi-automatic identification from reviews)]
4-trimethylaminobutyraldehyde dehydrogenase; TMABADH; 1.2.1.47 (Aldehyde dehydrogenase E3 isozyme; Aldehyde dehydrogenase family 9 member A1; 1.2.1.3; Gamma-aminobutyraldehyde dehydrogenase; 1.2.1.19; R-aminobutyraldehyde dehydrogenase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
4-trimethylaminobutyraldehyde dehydrogenase; TMABADH; 1.2.1.47 (Aldehyde dehydrogenase E3 isozyme; Aldehyde dehydrogenase family 9 member A1; 1.2.1.3; Gamma-aminobutyraldehyde dehydrogenase; 1.2.1.19; R-aminobutyraldehyde dehydrogenase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P49189
ID AL9A1_HUMAN Reviewed; 494 AA.
AC P49189; B2R6X1; Q5VV90; Q6LCL1; Q9NZT7;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-2005, sequence version 3.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=4-trimethylaminobutyraldehyde dehydrogenase;
DE Short=TMABADH;
DE EC=1.2.1.47;
DE AltName: Full=Aldehyde dehydrogenase E3 isozyme;
DE AltName: Full=Aldehyde dehydrogenase family 9 member A1;
DE EC=1.2.1.3;
DE AltName: Full=Gamma-aminobutyraldehyde dehydrogenase;
DE EC=1.2.1.19;
DE AltName: Full=R-aminobutyraldehyde dehydrogenase;
GN Name=ALDH9A1; Synonyms=ALDH4, ALDH7, ALDH9;
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 SER-116.
RC TISSUE=Liver;
RX PubMed=8786138; DOI=10.1006/geno.1996.0300;
RA Lin S.W., Chen J.C., Hsu L.C., Hsieh C.-L., Yoshida A.;
RT "Human gamma-aminobutyraldehyde dehydrogenase (ALDH9): cDNA sequence,
RT genomic organization, polymorphism, chromosomal localization, and
RT tissue expression.";
RL Genomics 34:376-380(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=10702312; DOI=10.1074/jbc.275.10.7390;
RA Vaz F.M., Fouchier S.W., Ofman R., Sommer M., Wanders R.J.A.;
RT "Molecular and biochemical characterization of rat gamma-
RT trimethylaminobutyraldehyde dehydrogenase and evidence for the
RT involvement of human aldehyde dehydrogenase 9 in carnitine
RT biosynthesis.";
RL J. Biol. Chem. 275:7390-7394(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP PROTEIN SEQUENCE OF 2-15; 247-258; 299-310; 315-326 AND 472-481,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Gottlieb E.;
RL Submitted (MAR-2008) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 259-274; 353-366; 412-426 AND 434-453, NUCLEOTIDE
RP SEQUENCE [MRNA] OF 29-494, CHARACTERIZATION, TISSUE SPECIFICITY, AND
RP VARIANT SER-116.
RC TISSUE=Brain;
RX PubMed=8645224;
RA Kikonyogo A., Pietruszko R.;
RT "Aldehyde dehydrogenase from adult human brain that dehydrogenates
RT gamma-aminobutyraldehyde: purification, characterization, cloning and
RT distribution.";
RL Biochem. J. 316:317-324(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 33-494, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8269919; DOI=10.1111/j.1432-1033.1993.tb18379.x;
RA Kurys G., Shah P.C., Kikonyogo A., Reed D., Ambroziak W.,
RA Pietruszko R.;
RT "Human aldehyde dehydrogenase. cDNA cloning and primary structure of
RT the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde.";
RL Eur. J. Biochem. 218:311-320(1993).
RN [8]
RP CHARACTERIZATION.
RC TISSUE=Liver;
RX PubMed=2925663;
RA Kurys G., Ambroziak W., Pietruszko R.;
RT "Human aldehyde dehydrogenase. Purification and characterization of a
RT third isozyme with low Km for gamma-aminobutyraldehyde.";
RL J. Biol. Chem. 264:4715-4721(1989).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-298, AND MASS 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 [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
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).
CC -!- FUNCTION: Converts gamma-trimethylaminobutyraldehyde into gamma-
CC butyrobetaine. Catalyzes the irreversible oxidation of a broad
CC range of aldehydes to the corresponding acids in an NAD-dependent
CC reaction.
CC -!- CATALYTIC ACTIVITY: 4-trimethylammoniobutanal + NAD(+) + H(2)O =
CC 4-trimethylammoniobutanoate + NADH.
CC -!- CATALYTIC ACTIVITY: An aldehyde + NAD(+) + H(2)O = a carboxylate +
CC NADH.
CC -!- CATALYTIC ACTIVITY: 4-aminobutanal + NAD(+) + H(2)O = 4-
CC aminobutanoate + NADH.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11 uM for 4-aminobutyraldehyde;
CC pH dependence:
CC Optimum pH is about 9.4 with propionaldehyde as substrate, and
CC 7.5 with 4-aminobutyraldehyde as substrate;
CC -!- PATHWAY: Amine and polyamine biosynthesis; carnitine biosynthesis.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- TISSUE SPECIFICITY: High expression in adult liver, skeletal
CC muscle, and kidney. Low levels in heart, pancreas, lung and brain.
CC Expressed in all regions of the brain. Expression levels are
CC variable in the different brain areas, with the highest levels in
CC the spinal cord and the lowest in the occipital pole.
CC -!- DEVELOPMENTAL STAGE: Strongly expressed in human embryonic brain
CC (gestational age 12 weeks).
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH74061.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; U34252; AAB18827.1; -; mRNA.
DR EMBL; AF172093; AAF43600.1; -; mRNA.
DR EMBL; AK312751; BAG35618.1; -; mRNA.
DR EMBL; AL451074; CAH74061.1; ALT_INIT; Genomic_DNA.
DR EMBL; U50203; AAB06721.1; -; mRNA.
DR EMBL; X75425; CAA53176.1; -; mRNA.
DR PIR; G02054; S39532.
DR RefSeq; NP_000687.3; NM_000696.3.
DR UniGene; Hs.2533; -.
DR ProteinModelPortal; P49189; -.
DR SMR; P49189; 2-494.
DR IntAct; P49189; 5.
DR MINT; MINT-5006004; -.
DR STRING; 9606.ENSP00000346827; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P49189; -.
DR DMDM; 62511242; -.
DR REPRODUCTION-2DPAGE; IPI00479877; -.
DR PaxDb; P49189; -.
DR PRIDE; P49189; -.
DR DNASU; 223; -.
DR Ensembl; ENST00000354775; ENSP00000346827; ENSG00000143149.
DR GeneID; 223; -.
DR KEGG; hsa:223; -.
DR UCSC; uc010pky.1; human.
DR CTD; 223; -.
DR GeneCards; GC01M165632; -.
DR H-InvDB; HIX0199965; -.
DR HGNC; HGNC:412; ALDH9A1.
DR HPA; HPA010873; -.
DR MIM; 602733; gene.
DR neXtProt; NX_P49189; -.
DR PharmGKB; PA24706; -.
DR eggNOG; COG1012; -.
DR HOVERGEN; HBG000097; -.
DR InParanoid; P49189; -.
DR KO; K00149; -.
DR OrthoDB; EOG7327P4; -.
DR PhylomeDB; P49189; -.
DR BioCyc; MetaCyc:HS06992-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P49189; -.
DR UniPathway; UPA00118; -.
DR ChiTaRS; ALDH9A1; human.
DR GeneWiki; Aldehyde_dehydrogenase_9_family,_member_A1; -.
DR GenomeRNAi; 223; -.
DR NextBio; 906; -.
DR PRO; PR:P49189; -.
DR ArrayExpress; P49189; -.
DR Bgee; P49189; -.
DR CleanEx; HS_ALDH9A1; -.
DR Genevestigator; P49189; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0033737; F:1-pyrroline dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; TAS:Reactome.
DR GO; GO:0047105; F:4-trimethylammoniobutyraldehyde dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0019145; F:aminobutyraldehyde dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0045329; P:carnitine biosynthetic process; TAS:Reactome.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; IDA:UniProtKB.
DR GO; GO:0042445; P:hormone metabolic process; TAS:UniProtKB.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; IDA:UniProtKB.
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 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; Complete proteome; Cytoplasm; Direct protein sequencing;
KW NAD; Oxidoreductase; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 494 4-trimethylaminobutyraldehyde
FT dehydrogenase.
FT /FTId=PRO_0000056485.
FT NP_BIND 232 237 NAD (By similarity).
FT ACT_SITE 254 254 Proton acceptor (By similarity).
FT ACT_SITE 288 288 Nucleophile (By similarity).
FT SITE 157 157 Transition state stabilizer (By
FT similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 30 30 N6-acetyllysine (By similarity).
FT MOD_RES 298 298 N6-acetyllysine.
FT MOD_RES 303 303 N6-acetyllysine (By similarity).
FT MOD_RES 344 344 N6-acetyllysine (By similarity).
FT VARIANT 116 116 C -> S (in allele ALDH9A1*2).
FT /FTId=VAR_011304.
FT CONFLICT 19 25 RVEPADA -> AGAGGR (in Ref. 1; AAB18827).
FT CONFLICT 150 150 C -> Q (in Ref. 7; AA sequence).
FT CONFLICT 159 159 P -> W (in Ref. 7; AA sequence).
FT CONFLICT 172 172 A -> R (in Ref. 7; AA sequence).
SQ SEQUENCE 494 AA; 53802 MW; 1E1CDF910D763BA1 CRC64;
MSTGTFVVSQ PLNYRGGARV EPADASGTEK AFEPATGRVI ATFTCSGEKE VNLAVQNAKA
AFKIWSQKSG MERCRILLEA ARIIREREDE IATMECINNG KSIFEARLDI DISWQCLEYY
AGLAASMAGE HIQLPGGSFG YTRREPLGVC VGIGAWNYPF QIASWKSAPA LACGNAMVFK
PSPFTPVSAL LLAEIYSEAG VPPGLFNVVQ GGAATGQFLC QHPDVAKVSF TGSVPTGMKI
MEMSAKGIKP VTLELGGKSP LIIFSDCDMN NAVKGALMAN FLTQGQVCCN GTRVFVQKEI
LDKFTEEVVK QTQRIKIGDP LLEDTRMGPL INRPHLERVL GFVKVAKEQG AKVLCGGDIY
VPEDPKLKDG YYMRPCVLTN CRDDMTCVKE EIFGPVMSIL SFDTEAEVLE RANDTTFGLA
AGVFTRDIQR AHRVVAELQA GTCFINNYNV SPVELPFGGY KKSGFGRENG RVTIEYYSQL
KTVCVEMGDV ESAF
//
ID AL9A1_HUMAN Reviewed; 494 AA.
AC P49189; B2R6X1; Q5VV90; Q6LCL1; Q9NZT7;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-2005, sequence version 3.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=4-trimethylaminobutyraldehyde dehydrogenase;
DE Short=TMABADH;
DE EC=1.2.1.47;
DE AltName: Full=Aldehyde dehydrogenase E3 isozyme;
DE AltName: Full=Aldehyde dehydrogenase family 9 member A1;
DE EC=1.2.1.3;
DE AltName: Full=Gamma-aminobutyraldehyde dehydrogenase;
DE EC=1.2.1.19;
DE AltName: Full=R-aminobutyraldehyde dehydrogenase;
GN Name=ALDH9A1; Synonyms=ALDH4, ALDH7, ALDH9;
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 SER-116.
RC TISSUE=Liver;
RX PubMed=8786138; DOI=10.1006/geno.1996.0300;
RA Lin S.W., Chen J.C., Hsu L.C., Hsieh C.-L., Yoshida A.;
RT "Human gamma-aminobutyraldehyde dehydrogenase (ALDH9): cDNA sequence,
RT genomic organization, polymorphism, chromosomal localization, and
RT tissue expression.";
RL Genomics 34:376-380(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=10702312; DOI=10.1074/jbc.275.10.7390;
RA Vaz F.M., Fouchier S.W., Ofman R., Sommer M., Wanders R.J.A.;
RT "Molecular and biochemical characterization of rat gamma-
RT trimethylaminobutyraldehyde dehydrogenase and evidence for the
RT involvement of human aldehyde dehydrogenase 9 in carnitine
RT biosynthesis.";
RL J. Biol. Chem. 275:7390-7394(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP PROTEIN SEQUENCE OF 2-15; 247-258; 299-310; 315-326 AND 472-481,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Heiserich L., Gottlieb E.;
RL Submitted (MAR-2008) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 259-274; 353-366; 412-426 AND 434-453, NUCLEOTIDE
RP SEQUENCE [MRNA] OF 29-494, CHARACTERIZATION, TISSUE SPECIFICITY, AND
RP VARIANT SER-116.
RC TISSUE=Brain;
RX PubMed=8645224;
RA Kikonyogo A., Pietruszko R.;
RT "Aldehyde dehydrogenase from adult human brain that dehydrogenates
RT gamma-aminobutyraldehyde: purification, characterization, cloning and
RT distribution.";
RL Biochem. J. 316:317-324(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 33-494, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8269919; DOI=10.1111/j.1432-1033.1993.tb18379.x;
RA Kurys G., Shah P.C., Kikonyogo A., Reed D., Ambroziak W.,
RA Pietruszko R.;
RT "Human aldehyde dehydrogenase. cDNA cloning and primary structure of
RT the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde.";
RL Eur. J. Biochem. 218:311-320(1993).
RN [8]
RP CHARACTERIZATION.
RC TISSUE=Liver;
RX PubMed=2925663;
RA Kurys G., Ambroziak W., Pietruszko R.;
RT "Human aldehyde dehydrogenase. Purification and characterization of a
RT third isozyme with low Km for gamma-aminobutyraldehyde.";
RL J. Biol. Chem. 264:4715-4721(1989).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-298, AND MASS 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 [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
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).
CC -!- FUNCTION: Converts gamma-trimethylaminobutyraldehyde into gamma-
CC butyrobetaine. Catalyzes the irreversible oxidation of a broad
CC range of aldehydes to the corresponding acids in an NAD-dependent
CC reaction.
CC -!- CATALYTIC ACTIVITY: 4-trimethylammoniobutanal + NAD(+) + H(2)O =
CC 4-trimethylammoniobutanoate + NADH.
CC -!- CATALYTIC ACTIVITY: An aldehyde + NAD(+) + H(2)O = a carboxylate +
CC NADH.
CC -!- CATALYTIC ACTIVITY: 4-aminobutanal + NAD(+) + H(2)O = 4-
CC aminobutanoate + NADH.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11 uM for 4-aminobutyraldehyde;
CC pH dependence:
CC Optimum pH is about 9.4 with propionaldehyde as substrate, and
CC 7.5 with 4-aminobutyraldehyde as substrate;
CC -!- PATHWAY: Amine and polyamine biosynthesis; carnitine biosynthesis.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- TISSUE SPECIFICITY: High expression in adult liver, skeletal
CC muscle, and kidney. Low levels in heart, pancreas, lung and brain.
CC Expressed in all regions of the brain. Expression levels are
CC variable in the different brain areas, with the highest levels in
CC the spinal cord and the lowest in the occipital pole.
CC -!- DEVELOPMENTAL STAGE: Strongly expressed in human embryonic brain
CC (gestational age 12 weeks).
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAH74061.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U34252; AAB18827.1; -; mRNA.
DR EMBL; AF172093; AAF43600.1; -; mRNA.
DR EMBL; AK312751; BAG35618.1; -; mRNA.
DR EMBL; AL451074; CAH74061.1; ALT_INIT; Genomic_DNA.
DR EMBL; U50203; AAB06721.1; -; mRNA.
DR EMBL; X75425; CAA53176.1; -; mRNA.
DR PIR; G02054; S39532.
DR RefSeq; NP_000687.3; NM_000696.3.
DR UniGene; Hs.2533; -.
DR ProteinModelPortal; P49189; -.
DR SMR; P49189; 2-494.
DR IntAct; P49189; 5.
DR MINT; MINT-5006004; -.
DR STRING; 9606.ENSP00000346827; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P49189; -.
DR DMDM; 62511242; -.
DR REPRODUCTION-2DPAGE; IPI00479877; -.
DR PaxDb; P49189; -.
DR PRIDE; P49189; -.
DR DNASU; 223; -.
DR Ensembl; ENST00000354775; ENSP00000346827; ENSG00000143149.
DR GeneID; 223; -.
DR KEGG; hsa:223; -.
DR UCSC; uc010pky.1; human.
DR CTD; 223; -.
DR GeneCards; GC01M165632; -.
DR H-InvDB; HIX0199965; -.
DR HGNC; HGNC:412; ALDH9A1.
DR HPA; HPA010873; -.
DR MIM; 602733; gene.
DR neXtProt; NX_P49189; -.
DR PharmGKB; PA24706; -.
DR eggNOG; COG1012; -.
DR HOVERGEN; HBG000097; -.
DR InParanoid; P49189; -.
DR KO; K00149; -.
DR OrthoDB; EOG7327P4; -.
DR PhylomeDB; P49189; -.
DR BioCyc; MetaCyc:HS06992-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P49189; -.
DR UniPathway; UPA00118; -.
DR ChiTaRS; ALDH9A1; human.
DR GeneWiki; Aldehyde_dehydrogenase_9_family,_member_A1; -.
DR GenomeRNAi; 223; -.
DR NextBio; 906; -.
DR PRO; PR:P49189; -.
DR ArrayExpress; P49189; -.
DR Bgee; P49189; -.
DR CleanEx; HS_ALDH9A1; -.
DR Genevestigator; P49189; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0033737; F:1-pyrroline dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; TAS:Reactome.
DR GO; GO:0047105; F:4-trimethylammoniobutyraldehyde dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0019145; F:aminobutyraldehyde dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0045329; P:carnitine biosynthetic process; TAS:Reactome.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; IDA:UniProtKB.
DR GO; GO:0042445; P:hormone metabolic process; TAS:UniProtKB.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; IDA:UniProtKB.
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 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; Complete proteome; Cytoplasm; Direct protein sequencing;
KW NAD; Oxidoreductase; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 494 4-trimethylaminobutyraldehyde
FT dehydrogenase.
FT /FTId=PRO_0000056485.
FT NP_BIND 232 237 NAD (By similarity).
FT ACT_SITE 254 254 Proton acceptor (By similarity).
FT ACT_SITE 288 288 Nucleophile (By similarity).
FT SITE 157 157 Transition state stabilizer (By
FT similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 30 30 N6-acetyllysine (By similarity).
FT MOD_RES 298 298 N6-acetyllysine.
FT MOD_RES 303 303 N6-acetyllysine (By similarity).
FT MOD_RES 344 344 N6-acetyllysine (By similarity).
FT VARIANT 116 116 C -> S (in allele ALDH9A1*2).
FT /FTId=VAR_011304.
FT CONFLICT 19 25 RVEPADA -> AGAGGR (in Ref. 1; AAB18827).
FT CONFLICT 150 150 C -> Q (in Ref. 7; AA sequence).
FT CONFLICT 159 159 P -> W (in Ref. 7; AA sequence).
FT CONFLICT 172 172 A -> R (in Ref. 7; AA sequence).
SQ SEQUENCE 494 AA; 53802 MW; 1E1CDF910D763BA1 CRC64;
MSTGTFVVSQ PLNYRGGARV EPADASGTEK AFEPATGRVI ATFTCSGEKE VNLAVQNAKA
AFKIWSQKSG MERCRILLEA ARIIREREDE IATMECINNG KSIFEARLDI DISWQCLEYY
AGLAASMAGE HIQLPGGSFG YTRREPLGVC VGIGAWNYPF QIASWKSAPA LACGNAMVFK
PSPFTPVSAL LLAEIYSEAG VPPGLFNVVQ GGAATGQFLC QHPDVAKVSF TGSVPTGMKI
MEMSAKGIKP VTLELGGKSP LIIFSDCDMN NAVKGALMAN FLTQGQVCCN GTRVFVQKEI
LDKFTEEVVK QTQRIKIGDP LLEDTRMGPL INRPHLERVL GFVKVAKEQG AKVLCGGDIY
VPEDPKLKDG YYMRPCVLTN CRDDMTCVKE EIFGPVMSIL SFDTEAEVLE RANDTTFGLA
AGVFTRDIQR AHRVVAELQA GTCFINNYNV SPVELPFGGY KKSGFGRENG RVTIEYYSQL
KTVCVEMGDV ESAF
//
MIM
602733
*RECORD*
*FIELD* NO
602733
*FIELD* TI
*602733 ALDEHYDE DEHYDROGENASE, FAMILY 9, SUBFAMILY A, MEMBER 1; ALDH9A1
;;ALDEHYDE DEHYDROGENASE 9; ALDH9;;
read moreE3
*FIELD* TX
DESCRIPTION
The aldehyde dehydrogenases (EC 1.2.1.3) are a family of isozymes that
catalyze the oxidation of a broad range of aldehydes and the
dehydrogenation of aldehyde metabolites of compounds such as
corticosteroids and biogenic amines. The aldehyde dehydrogenase E3
catalyzes the dehydrogenation of gamma-aminobutyraldehyde to
gamma-aminobutyric acid (GABA) (summary by Kurys et al., 1989).
CLONING
Kurys et al. (1989) identified a liver aldehyde dehydrogenase isozyme,
which they called E3, that catalyzes the dehydrogenation of
gamma-aminobutyraldehyde to gamma-aminobutyric acid. By SDS-PAGE and
gradient gel electrophoresis, they found that E3 is a tetramer of
identical 54-kD subunits. Using antibodies against E3 to screen a liver
cDNA library, Kurys et al. (1993) isolated partial E3 cDNAs.
Lin et al. (1996) isolated cDNAs containing the complete ALDH9 coding
region, and found that the gene encodes a predicted 493-amino acid
protein. These authors stated that their nucleotide sequence differs
from that of Kurys et al. (1993) in 3 positions. By sequence analysis of
the ALDH9 locus in several unrelated individuals, Lin et al. (1996)
determined that 2 of the differences were due to polymorphism. They
attributed the third difference to a misprint in Kurys et al. (1993).
Northern blot analysis revealed that ALDH9 is expressed as a 2.4-kb mRNA
in a variety of tissues, with the highest levels of expression in liver,
skeletal muscle, and kidney.
To study the role of E3 in the synthesis of the central nervous system
inhibitory neurotransmitter GABA, Kikonyogo and Pietruszko (1996)
characterized the E3 expression pattern in brain. By Northern blot
analysis, they found that E3 is expressed as a 2.9-kb mRNA in all
regions of the brain, with the highest levels in the spinal cord.
GENE STRUCTURE
Lin et al. (1996) reported that the ALDH9 gene contains 10 exons and
spans approximately 45 kb.
MAPPING
By analysis of a somatic cell hybrid panel, McPherson et al. (1994)
localized the E3 gene to chromosome 1. Using fluorescence in situ
hybridization, Lin et al. (1996) mapped the ALDH9 gene to 1q22-q23.
NOMENCLATURE
Vasiliou et al. (1999) discussed the eukaryotic aldehyde dehydrogenases,
tabulated all known human polymorphisms, and recommended nomenclature
based on divergent evolution and chromosomal mapping. They suggested
that the symbol ALDH9 (the 'trivial' designation) be changed to ALDH9A1.
*FIELD* AV
.0001
ALDH9A1*2 POLYMORPHISM
ALDH9A1, CYS115SER
Lin et al. (1996) observed a polymorphism in exon 2 of the ALDH9 gene
leading to a cys115-to-ser amino acid substitution. The wildtype allele
was designated ALDH9A1*1 and the 115-ser allele was designated
ALDH9A1*2.
*FIELD* RF
1. Kikonyogo, A.; Pietruszko, R.: Aldehyde dehydrogenase from adult
human brain that dehydrogenates gamma-aminobutyraldehyde: purification,
characterization, cloning and distribution. Biochem. J. 316: 317-324,
1996.
2. Kurys, G.; Ambroziak, W.; Pietruszko, R.: Human aldehyde dehydrogenase:
purification and characterization of a third isozyme with low Km for
gamma-aminobutyraldehyde. J. Biol. Chem. 264: 4715-4721, 1989.
3. Kurys, G.; Shah, P. C.; Kikonyogo, A.; Reed, D.; Ambroziak, W.;
Pietruszko, R.: Human aldehyde dehydrogenase: cDNA cloning and primary
structure of the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde. Europ.
J. Biochem. 218: 311-320, 1993.
4. Lin, S. W.; Chen, J. C.; Hsu, L. C.; Hsieh, C.-L.; Yoshida, A.
: Human gamma-aminobutyraldehyde dehydrogenase (ALDH9): cDNA sequence,
genomic organization, polymorphism, chromosomal localization, and
tissue expression. Genomics 34: 376-380, 1996.
5. McPherson, J. D.; Wasmuth, J. J.; Kurys, G.; Pietruszko, R.: Human
aldehyde dehydrogenase: chromosomal assignment of the gene for the
isozyme that metabolizes gamma-aminobutyraldehyde. Hum. Genet. 93:
211-212, 1994.
6. 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: 11/4/1999
*FIELD* CD
Rebekah S. Rasooly: 6/19/1998
*FIELD* ED
carol: 06/18/2012
carol: 6/12/2012
carol: 4/3/2001
carol: 11/9/1999
terry: 11/4/1999
alopez: 6/19/1998
*RECORD*
*FIELD* NO
602733
*FIELD* TI
*602733 ALDEHYDE DEHYDROGENASE, FAMILY 9, SUBFAMILY A, MEMBER 1; ALDH9A1
;;ALDEHYDE DEHYDROGENASE 9; ALDH9;;
read moreE3
*FIELD* TX
DESCRIPTION
The aldehyde dehydrogenases (EC 1.2.1.3) are a family of isozymes that
catalyze the oxidation of a broad range of aldehydes and the
dehydrogenation of aldehyde metabolites of compounds such as
corticosteroids and biogenic amines. The aldehyde dehydrogenase E3
catalyzes the dehydrogenation of gamma-aminobutyraldehyde to
gamma-aminobutyric acid (GABA) (summary by Kurys et al., 1989).
CLONING
Kurys et al. (1989) identified a liver aldehyde dehydrogenase isozyme,
which they called E3, that catalyzes the dehydrogenation of
gamma-aminobutyraldehyde to gamma-aminobutyric acid. By SDS-PAGE and
gradient gel electrophoresis, they found that E3 is a tetramer of
identical 54-kD subunits. Using antibodies against E3 to screen a liver
cDNA library, Kurys et al. (1993) isolated partial E3 cDNAs.
Lin et al. (1996) isolated cDNAs containing the complete ALDH9 coding
region, and found that the gene encodes a predicted 493-amino acid
protein. These authors stated that their nucleotide sequence differs
from that of Kurys et al. (1993) in 3 positions. By sequence analysis of
the ALDH9 locus in several unrelated individuals, Lin et al. (1996)
determined that 2 of the differences were due to polymorphism. They
attributed the third difference to a misprint in Kurys et al. (1993).
Northern blot analysis revealed that ALDH9 is expressed as a 2.4-kb mRNA
in a variety of tissues, with the highest levels of expression in liver,
skeletal muscle, and kidney.
To study the role of E3 in the synthesis of the central nervous system
inhibitory neurotransmitter GABA, Kikonyogo and Pietruszko (1996)
characterized the E3 expression pattern in brain. By Northern blot
analysis, they found that E3 is expressed as a 2.9-kb mRNA in all
regions of the brain, with the highest levels in the spinal cord.
GENE STRUCTURE
Lin et al. (1996) reported that the ALDH9 gene contains 10 exons and
spans approximately 45 kb.
MAPPING
By analysis of a somatic cell hybrid panel, McPherson et al. (1994)
localized the E3 gene to chromosome 1. Using fluorescence in situ
hybridization, Lin et al. (1996) mapped the ALDH9 gene to 1q22-q23.
NOMENCLATURE
Vasiliou et al. (1999) discussed the eukaryotic aldehyde dehydrogenases,
tabulated all known human polymorphisms, and recommended nomenclature
based on divergent evolution and chromosomal mapping. They suggested
that the symbol ALDH9 (the 'trivial' designation) be changed to ALDH9A1.
*FIELD* AV
.0001
ALDH9A1*2 POLYMORPHISM
ALDH9A1, CYS115SER
Lin et al. (1996) observed a polymorphism in exon 2 of the ALDH9 gene
leading to a cys115-to-ser amino acid substitution. The wildtype allele
was designated ALDH9A1*1 and the 115-ser allele was designated
ALDH9A1*2.
*FIELD* RF
1. Kikonyogo, A.; Pietruszko, R.: Aldehyde dehydrogenase from adult
human brain that dehydrogenates gamma-aminobutyraldehyde: purification,
characterization, cloning and distribution. Biochem. J. 316: 317-324,
1996.
2. Kurys, G.; Ambroziak, W.; Pietruszko, R.: Human aldehyde dehydrogenase:
purification and characterization of a third isozyme with low Km for
gamma-aminobutyraldehyde. J. Biol. Chem. 264: 4715-4721, 1989.
3. Kurys, G.; Shah, P. C.; Kikonyogo, A.; Reed, D.; Ambroziak, W.;
Pietruszko, R.: Human aldehyde dehydrogenase: cDNA cloning and primary
structure of the enzyme that catalyzes dehydrogenation of 4-aminobutyraldehyde. Europ.
J. Biochem. 218: 311-320, 1993.
4. Lin, S. W.; Chen, J. C.; Hsu, L. C.; Hsieh, C.-L.; Yoshida, A.
: Human gamma-aminobutyraldehyde dehydrogenase (ALDH9): cDNA sequence,
genomic organization, polymorphism, chromosomal localization, and
tissue expression. Genomics 34: 376-380, 1996.
5. McPherson, J. D.; Wasmuth, J. J.; Kurys, G.; Pietruszko, R.: Human
aldehyde dehydrogenase: chromosomal assignment of the gene for the
isozyme that metabolizes gamma-aminobutyraldehyde. Hum. Genet. 93:
211-212, 1994.
6. 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: 11/4/1999
*FIELD* CD
Rebekah S. Rasooly: 6/19/1998
*FIELD* ED
carol: 06/18/2012
carol: 6/12/2012
carol: 4/3/2001
carol: 11/9/1999
terry: 11/4/1999
alopez: 6/19/1998