AL9A1_MOUSE
ID AL9A1_MOUSE Reviewed; 494 AA.
AC Q9JLJ2; Q3U367;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=4-trimethylaminobutyraldehyde dehydrogenase;
DE Short=TMABA-DH;
DE Short=TMABADH;
DE EC=1.2.1.47 {ECO:0000250|UniProtKB:P49189};
DE AltName: Full=Aldehyde dehydrogenase family 9 member A1;
DE EC=1.2.1.3 {ECO:0000250|UniProtKB:P49189};
GN Name=Aldh9a1 {ECO:0000312|MGI:MGI:1861622};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 involvement
RT of human aldehyde dehydrogenase 9 in carnitine biosynthesis.";
RL J. Biol. Chem. 275:7390-7394(2000).
RN [2] {ECO:0000312|EMBL:BAE32922.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE28979.1}, and
RC NOD {ECO:0000312|EMBL:BAE32922.1};
RC TISSUE=Epididymis {ECO:0000312|EMBL:BAE36870.1}, and
RC Liver {ECO:0000312|EMBL:BAE28979.1};
RX PubMed=12466851; DOI=10.1038/nature01266;
RA Okazaki Y., Furuno M., Kasukawa T., Adachi J., Bono H., Kondo S.,
RA Nikaido I., Osato N., Saito R., Suzuki H., Yamanaka I., Kiyosawa H.,
RA Yagi K., Tomaru Y., Hasegawa Y., Nogami A., Schonbach C., Gojobori T.,
RA Baldarelli R., Hill D.P., Bult C., Hume D.A., Quackenbush J., Schriml L.M.,
RA Kanapin A., Matsuda H., Batalov S., Beisel K.W., Blake J.A., Bradt D.,
RA Brusic V., Chothia C., Corbani L.E., Cousins S., Dalla E., Dragani T.A.,
RA Fletcher C.F., Forrest A., Frazer K.S., Gaasterland T., Gariboldi M.,
RA Gissi C., Godzik A., Gough J., Grimmond S., Gustincich S., Hirokawa N.,
RA Jackson I.J., Jarvis E.D., Kanai A., Kawaji H., Kawasawa Y.,
RA Kedzierski R.M., King B.L., Konagaya A., Kurochkin I.V., Lee Y.,
RA Lenhard B., Lyons P.A., Maglott D.R., Maltais L., Marchionni L.,
RA McKenzie L., Miki H., Nagashima T., Numata K., Okido T., Pavan W.J.,
RA Pertea G., Pesole G., Petrovsky N., Pillai R., Pontius J.U., Qi D.,
RA Ramachandran S., Ravasi T., Reed J.C., Reed D.J., Reid J., Ring B.Z.,
RA Ringwald M., Sandelin A., Schneider C., Semple C.A., Setou M., Shimada K.,
RA Sultana R., Takenaka Y., Taylor M.S., Teasdale R.D., Tomita M., Verardo R.,
RA Wagner L., Wahlestedt C., Wang Y., Watanabe Y., Wells C., Wilming L.G.,
RA Wynshaw-Boris A., Yanagisawa M., Yang I., Yang L., Yuan Z., Zavolan M.,
RA Zhu Y., Zimmer A., Carninci P., Hayatsu N., Hirozane-Kishikawa T.,
RA Konno H., Nakamura M., Sakazume N., Sato K., Shiraki T., Waki K., Kawai J.,
RA Aizawa K., Arakawa T., Fukuda S., Hara A., Hashizume W., Imotani K.,
RA Ishii Y., Itoh M., Kagawa I., Miyazaki A., Sakai K., Sasaki D., Shibata K.,
RA Shinagawa A., Yasunishi A., Yoshino M., Waterston R., Lander E.S.,
RA Rogers J., Birney E., Hayashizaki Y.;
RT "Analysis of the mouse transcriptome based on functional annotation of
RT 60,770 full-length cDNAs.";
RL Nature 420:563-573(2002).
RN [3] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 39-59; 74-82; 88-101; 228-239; 247-274; 317-338;
RP 348-366; 412-426 AND 472-494, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-30; LYS-59 AND LYS-303, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-30; LYS-298; LYS-303 AND LYS-344,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Converts gamma-trimethylaminobutyraldehyde into gamma-
CC butyrobetaine with high efficiency (in vitro). Can catalyze the
CC irreversible oxidation of a broad range of aldehydes to the
CC corresponding acids in an NAD-dependent reaction, but with low
CC efficiency. {ECO:0000250|UniProtKB:P49189}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-(trimethylamino)butanal + H2O + NAD(+) = 4-
CC (trimethylamino)butanoate + 2 H(+) + NADH; Xref=Rhea:RHEA:17985,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16244,
CC ChEBI:CHEBI:18020, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.47;
CC Evidence={ECO:0000250|UniProtKB:P49189};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH;
CC Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.3;
CC Evidence={ECO:0000250|UniProtKB:P49189};
CC -!- PATHWAY: Amine and polyamine biosynthesis; carnitine biosynthesis.
CC {ECO:0000250|UniProtKB:P49189}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P49189}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9JLJ3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JLJ2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JLJ2-2; Sequence=VSP_061582;
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative initiation.
CC Contains a predicted signal peptide at positions 1-21. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AF170919; AAF43599.1; -; mRNA.
DR EMBL; BC003297; AAH03297.1; -; mRNA.
DR EMBL; AK149589; BAE28979.1; -; mRNA.
DR EMBL; AK162354; BAE36870.1; -; mRNA.
DR EMBL; AK154914; BAE32922.1; -; mRNA.
DR RefSeq; NP_064377.2; NM_019993.3.
DR AlphaFoldDB; Q9JLJ2; -.
DR SMR; Q9JLJ2; -.
DR BioGRID; 208163; 15.
DR IntAct; Q9JLJ2; 1.
DR MINT; Q9JLJ2; -.
DR STRING; 10090.ENSMUSP00000028004; -.
DR iPTMnet; Q9JLJ2; -.
DR PhosphoSitePlus; Q9JLJ2; -.
DR SwissPalm; Q9JLJ2; -.
DR REPRODUCTION-2DPAGE; Q9JLJ2; -.
DR EPD; Q9JLJ2; -.
DR jPOST; Q9JLJ2; -.
DR MaxQB; Q9JLJ2; -.
DR PaxDb; Q9JLJ2; -.
DR PRIDE; Q9JLJ2; -.
DR ProteomicsDB; 282071; -.
DR DNASU; 56752; -.
DR Ensembl; ENSMUST00000028004.11; ENSMUSP00000028004.10; ENSMUSG00000026687.15.
DR GeneID; 56752; -.
DR KEGG; mmu:56752; -.
DR UCSC; uc007dkx.1; mouse.
DR CTD; 223; -.
DR MGI; MGI:1861622; Aldh9a1.
DR VEuPathDB; HostDB:ENSMUSG00000026687; -.
DR eggNOG; KOG2450; Eukaryota.
DR GeneTree; ENSGT00940000162687; -.
DR InParanoid; Q9JLJ2; -.
DR OrthoDB; 538179at2759; -.
DR PhylomeDB; Q9JLJ2; -.
DR BRENDA; 1.2.1.47; 3474.
DR Reactome; R-MMU-71262; Carnitine synthesis.
DR UniPathway; UPA00118; -.
DR BioGRID-ORCS; 56752; 0 hits in 60 CRISPR screens.
DR ChiTaRS; Aldh9a1; mouse.
DR PRO; PR:Q9JLJ2; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9JLJ2; protein.
DR Bgee; ENSMUSG00000026687; Expressed in left lobe of liver and 276 other tissues.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0047105; F:4-trimethylammoniobutyraldehyde dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; ISO:MGI.
DR GO; GO:0043176; F:amine binding; ISO:MGI.
DR GO; GO:0019145; F:aminobutyraldehyde dehydrogenase activity; ISO:MGI.
DR GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051287; F:NAD binding; ISO:MGI.
DR GO; GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; IDA:MGI.
DR GO; GO:0045329; P:carnitine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009437; P:carnitine metabolic process; IDA:MGI.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; ISS:UniProtKB.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; ISO:MGI.
DR GO; GO:0051289; P:protein homotetramerization; ISS: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_CYS.
DR InterPro; IPR029510; Ald_DH_CS_GLU.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative initiation; Cytoplasm; Direct protein sequencing;
KW NAD; Oxidoreductase; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P49189"
FT CHAIN 2..494
FT /note="4-trimethylaminobutyraldehyde dehydrogenase"
FT /id="PRO_0000056486"
FT ACT_SITE 254
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT ACT_SITE 288
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 180
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P56533"
FT BINDING 232..236
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P56533"
FT BINDING 391
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P56533"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P49189"
FT MOD_RES 30
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 30
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 59
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 298
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 303
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 303
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 344
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT VAR_SEQ 1
FT /note="M -> MILGAVGSVLTSLLRIHRAAAVAAM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_061582"
SQ SEQUENCE 494 AA; 53515 MW; CBB27755330E0A23 CRC64;
MSTGTFVVSQ PLNYRGGARV EPVDASGTEK AFEPATGRVI ATFACSGEKE VNLAVENAKA
AFKLWSKKSG LERCQVLLEA ARIIKERKDE IATVETINNG KSIFEARLDV DTCWQCLEYY
AGLAASMAGE HIQLPGGSFG YTRREPLGVC VGIGAWNYPF QIACWKSAPA LACGNAMIFK
PSPFTPVSAL LLAEIYTKAG APPGLFNVVQ GGAATGQFLC HHREVAKISF TGSVPTGVKI
MEMSAKGVKP ITLELGGKSP LIIFSDCNME NAVKGALMAN FLTQGQVCCN GTRVFVQKEI
ADKFINEVVK QTQKIKLGDP LLEDTRMGPL INAPHLERVL GFVKLAKEQG ATVLCGGEVY
VPEDPKLKHG YYMTPCILTN CRDDMTCVKE EIFGPVMSIL TFGTEAEVLE RANDTTFGLA
AGVFTRDIQR AHRVAAELQA GTCYINNYNV SPVELPFGGY KKSGFGRENG RVTIEYYSQL
KTVCVEMGDV ESAF
