AL7A1_RAT
ID AL7A1_RAT Reviewed; 539 AA.
AC Q64057;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Alpha-aminoadipic semialdehyde dehydrogenase;
DE Short=Alpha-AASA dehydrogenase;
DE EC=1.2.1.31 {ECO:0000250|UniProtKB:P49419};
DE AltName: Full=Aldehyde dehydrogenase family 7 member A1;
DE EC=1.2.1.3 {ECO:0000250|UniProtKB:P49419};
DE AltName: Full=Antiquitin-1;
DE AltName: Full=Betaine aldehyde dehydrogenase;
DE EC=1.2.1.8 {ECO:0000250|UniProtKB:P49419};
DE AltName: Full=Delta1-piperideine-6-carboxylate dehydrogenase;
DE Short=P6c dehydrogenase;
DE Flags: Precursor;
GN Name=Aldh7a1 {ECO:0000312|RGD:1308614}; Synonyms=Ald7a1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000305};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP PROTEIN SEQUENCE OF 53-66 AND 144-154, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 312-539, AND TISSUE SPECIFICITY.
RC TISSUE=Intestinal mucosa;
RX PubMed=8088832; DOI=10.1006/geno.1994.1279;
RA Lee P., Kuhl W., Gelbart T., Kamimura T., West C., Beutler E.;
RT "Homology between a human protein and a protein of the green garden pea.";
RL Genomics 21:371-378(1994).
RN [4] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=9417906; DOI=10.1006/geno.1997.5026;
RA Skvorak A.B., Robertson N.G., Yin Y., Weremowicz S., Her H., Bieber F.R.,
RA Beisel K.W., Lynch E.D., Beier D.R., Morton C.C.;
RT "An ancient conserved gene expressed in the human inner ear:
RT identification, expression analysis, and chromosomal mapping of human and
RT mouse antiquitin (ATQ1).";
RL Genomics 46:191-199(1997).
CC -!- FUNCTION: Multifunctional enzyme mediating important protective
CC effects. Metabolizes betaine aldehyde to betaine, an important cellular
CC osmolyte and methyl donor. Protects cells from oxidative stress by
CC metabolizing a number of lipid peroxidation-derived aldehydes. Involved
CC in lysine catabolism. {ECO:0000250|UniProtKB:P49419}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) + nonanal = 2 H(+) + NADH + nonanoate;
CC Xref=Rhea:RHEA:69759, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32361, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:84268; Evidence={ECO:0000250|UniProtKB:P49419};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69760;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2-amino-6-oxohexanoate + H2O + NAD(+) = 2 H(+) + L-2-
CC aminoadipate + NADH; Xref=Rhea:RHEA:12308, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58321, ChEBI:CHEBI:58672; EC=1.2.1.31;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12309;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=betaine aldehyde + H2O + NAD(+) = glycine betaine + 2 H(+) +
CC NADH; Xref=Rhea:RHEA:15305, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15710, ChEBI:CHEBI:17750, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.8;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15306;
CC Evidence={ECO:0000250|UniProtKB:P49419};
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:P49419};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16186;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexanal + NAD(+) = 2 H(+) + hexanoate + NADH;
CC Xref=Rhea:RHEA:67276, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17120, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:88528; Evidence={ECO:0000250|UniProtKB:P49419};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67277;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) + octanal = 2 H(+) + NADH + octanoate;
CC Xref=Rhea:RHEA:44100, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17935, ChEBI:CHEBI:25646, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P49419};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44101;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-non-2-enal + H2O + NAD(+) = (E)-non-2-enoate + 2 H(+) +
CC NADH; Xref=Rhea:RHEA:69767, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:142592,
CC ChEBI:CHEBI:143908; Evidence={ECO:0000250|UniProtKB:P49419};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69768;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-4-hydroxynon-2-enal + H2O + NAD(+) = (E)-4-hydroxynon-2-
CC enoate + 2 H(+) + NADH; Xref=Rhea:RHEA:67248, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58968, ChEBI:CHEBI:142920;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67249;
CC Evidence={ECO:0000250|UniProtKB:P49419};
CC -!- PATHWAY: Amine and polyamine biosynthesis; betaine biosynthesis via
CC choline pathway; betaine from betaine aldehyde: step 1/1.
CC {ECO:0000250|UniProtKB:P49419}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P49419}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P49419}. Nucleus {ECO:0000250|UniProtKB:P49419}.
CC Mitochondrion {ECO:0000250|UniProtKB:P49419}.
CC -!- TISSUE SPECIFICITY: Abundant in kidney, liver, cochlea and outer hair
CC cells but not inner hair cells or vestibular type I hair cells. Very
CC low levels in lung, brain, intestine and pancreas.
CC {ECO:0000269|PubMed:8088832, ECO:0000269|PubMed:9417906}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AABR03109709; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; S75019; AAB31967.2; -; mRNA.
DR PIR; B54676; B54676.
DR RefSeq; NP_001258034.1; NM_001271105.1.
DR AlphaFoldDB; Q64057; -.
DR SMR; Q64057; -.
DR BioGRID; 253522; 1.
DR STRING; 10116.ENSRNOP00000020325; -.
DR iPTMnet; Q64057; -.
DR PhosphoSitePlus; Q64057; -.
DR jPOST; Q64057; -.
DR PaxDb; Q64057; -.
DR PRIDE; Q64057; -.
DR Ensembl; ENSRNOT00000020325; ENSRNOP00000020325; ENSRNOG00000014645.
DR GeneID; 291450; -.
DR KEGG; rno:291450; -.
DR UCSC; RGD:1308614; rat.
DR CTD; 501; -.
DR RGD; 1308614; Aldh7a1.
DR eggNOG; KOG2453; Eukaryota.
DR GeneTree; ENSGT00940000154938; -.
DR HOGENOM; CLU_005391_1_2_1; -.
DR InParanoid; Q64057; -.
DR OMA; DAWKVYM; -.
DR OrthoDB; 692580at2759; -.
DR PhylomeDB; Q64057; -.
DR TreeFam; TF300388; -.
DR Reactome; R-RNO-6798163; Choline catabolism.
DR Reactome; R-RNO-71064; Lysine catabolism.
DR UniPathway; UPA00529; UER00386.
DR PRO; PR:Q64057; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000014645; Expressed in adult mammalian kidney and 19 other tissues.
DR Genevisible; Q64057; RN.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; ISS:UniProtKB.
DR GO; GO:0008802; F:betaine-aldehyde dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0004043; F:L-aminoadipate-semialdehyde dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0019285; P:glycine betaine biosynthetic process from choline; IEA:UniProtKB-UniPathway.
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; IPR029510; Ald_DH_CS_GLU.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR InterPro; IPR044638; ALDH7A1-like.
DR PANTHER; PTHR43521; PTHR43521; 1.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Mitochondrion; NAD;
KW Nucleus; Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 27..539
FT /note="Alpha-aminoadipic semialdehyde dehydrogenase"
FT /id="PRO_0000056492"
FT ACT_SITE 296
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT ACT_SITE 330
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT BINDING 192..194
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49419"
FT BINDING 218
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49419"
FT BINDING 258..259
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49419"
FT BINDING 274..279
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 274..275
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49419"
FT BINDING 296..297
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49419"
FT BINDING 331
FT /ligand="(S)-2-amino-6-oxohexanoate"
FT /ligand_id="ChEBI:CHEBI:58321"
FT /evidence="ECO:0000250|UniProtKB:P49419"
FT BINDING 427
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49419"
FT BINDING 489
FT /ligand="(S)-2-amino-6-oxohexanoate"
FT /ligand_id="ChEBI:CHEBI:58321"
FT /evidence="ECO:0000250|UniProtKB:P49419"
FT BINDING 490
FT /ligand="(S)-2-amino-6-oxohexanoate"
FT /ligand_id="ChEBI:CHEBI:58321"
FT /evidence="ECO:0000250|UniProtKB:P49419"
FT SITE 195
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 86
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBF1"
FT MOD_RES 86
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBF1"
FT MOD_RES 94
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBF1"
FT MOD_RES 94
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBF1"
FT MOD_RES 97
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBF1"
FT MOD_RES 97
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBF1"
FT MOD_RES 462
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBF1"
FT MOD_RES 500
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBF1"
FT MOD_RES 537
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBF1"
SQ SEQUENCE 539 AA; 58749 MW; 90F355B926582E77 CRC64;
MLRLARPLCV QTVKASKLSR LWSRPAALMS TLLIHHPQYA WLQDLGLRED NEGVFNGSWG
GRGEVITTYC PANNEPIARV RQASMKDYEE TIGKAKKAWN IWADIPAPKR GEIVRKIGDA
LREKIQLLGR LVSLEMGKIL VEGIGEVQEY VDVCDYAAGL SRMIGGPTLP SERPGHALME
QWNPLGLVGI ITAFNFPVAV FGWNNAIALI TGNVCLWKGA PTTSLVSIAV TKIIAKVLED
NLLPGAICSL TCGGADMGTA MARDERVNLL SFTGSTQVGK QVALMVQERF GKSLLELGGN
NAIIAFEDAD LSLVLPSALF AAVGTAGQRC TTVRRLFLHE SIHDEVVDRL KNAYSQIRVG
NPWDPNILYG PLHTKQAVSM FVQAVEEAKK EGGTVVYGGK VMDHPGNYVE PTIVTGLVHD
APIVHKETFA PILYVFKFKN EEEVFEWNNE VKQGLSSSIF TKDLGRIFRW LGPKGSDCGI
VNVNIPTSGA EIGGAFGGEK HTGGGRESGS DAWKQYMRRS TCTINYSTAL PLAQGIKFQ
