AL8A1_HUMAN
ID AL8A1_HUMAN Reviewed; 487 AA.
AC Q9H2A2; B7Z521; O60793; Q24JS9; Q53GT3; Q5TI80;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=2-aminomuconic semialdehyde dehydrogenase {ECO:0000305|PubMed:29703752};
DE EC=1.2.1.32 {ECO:0000269|PubMed:29703752};
DE AltName: Full=Aldehyde dehydrogenase 12;
DE AltName: Full=Aldehyde dehydrogenase family 8 member A1 {ECO:0000312|HGNC:HGNC:15471};
GN Name=ALDH8A1 {ECO:0000312|HGNC:HGNC:15471}; Synonyms=ALDH12;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=11007799; DOI=10.1074/jbc.m008027200;
RA Lin M., Napoli J.L.;
RT "cDNA cloning and expression of a human aldehyde dehydrogenase (ALDH)
RT active with 9-cis-retinal and identification of a rat ortholog, ALDH12.";
RL J. Biol. Chem. 275:40106-40112(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Kidney, and Liver;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-362, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-109; ASN-155 AND ARG-451,
RP AND PATHWAY.
RX PubMed=29703752; DOI=10.1074/jbc.ra118.003320;
RA Davis I., Yang Y., Wherritt D., Liu A.;
RT "Reassignment of the human aldehyde dehydrogenase ALDH8A1 (ALDH12) to the
RT kynurenine pathway in tryptophan catabolism.";
RL J. Biol. Chem. 293:9594-9603(2018).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidation of 2-aminomuconic
CC semialdehyde of the kynurenine metabolic pathway in L-tryptophan
CC degradation. {ECO:0000269|PubMed:29703752}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-aminomuconate 6-semialdehyde + H2O + NAD(+) = (2Z,4E)-2-
CC aminomuconate + 2 H(+) + NADH; Xref=Rhea:RHEA:14469,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:77634, ChEBI:CHEBI:77859; EC=1.2.1.32;
CC Evidence={ECO:0000269|PubMed:29703752};
CC -!- PATHWAY: Amino-acid degradation; L-kynurenine degradation.
CC {ECO:0000305|PubMed:29703752}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9H2A2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H2A2-2; Sequence=VSP_029972;
CC Name=3;
CC IsoId=Q9H2A2-3; Sequence=VSP_039759, VSP_039760;
CC Name=4;
CC IsoId=Q9H2A2-4; Sequence=VSP_043279;
CC -!- TISSUE SPECIFICITY: Highly expressed in adult kidney and liver.
CC Detected at lower levels in fetal liver and kidney.
CC {ECO:0000269|PubMed:11007799}.
CC -!- MISCELLANEOUS: [Isoform 2]: Lacks enzymatic activity. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
CC -!- CAUTION: Originally described as a retinal dehydrogenase based on its
CC ability to preferentially oxidize 9-cis-retinal (PubMed:11007799). It
CC has been reassigned to a 2-aminomuconic semialdehyde dehydrogenase
CC (PubMed:29703752). {ECO:0000269|PubMed:11007799,
CC ECO:0000269|PubMed:29703752}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI14474.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR EMBL; AF303134; AAG42417.1; -; mRNA.
DR EMBL; AK290784; BAF83473.1; -; mRNA.
DR EMBL; AK298325; BAH12757.1; -; mRNA.
DR EMBL; AK222848; BAD96568.1; -; mRNA.
DR EMBL; AL021939; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445190; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47985.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47986.1; -; Genomic_DNA.
DR EMBL; BC113862; AAI13863.1; -; mRNA.
DR EMBL; BC114473; AAI14474.1; ALT_SEQ; mRNA.
DR CCDS; CCDS5171.1; -. [Q9H2A2-1]
DR CCDS; CCDS5172.1; -. [Q9H2A2-2]
DR CCDS; CCDS55057.1; -. [Q9H2A2-4]
DR RefSeq; NP_001180409.1; NM_001193480.1. [Q9H2A2-4]
DR RefSeq; NP_072090.1; NM_022568.3. [Q9H2A2-1]
DR RefSeq; NP_739577.1; NM_170771.2. [Q9H2A2-2]
DR AlphaFoldDB; Q9H2A2; -.
DR SMR; Q9H2A2; -.
DR BioGRID; 122204; 26.
DR IntAct; Q9H2A2; 3.
DR STRING; 9606.ENSP00000265605; -.
DR iPTMnet; Q9H2A2; -.
DR PhosphoSitePlus; Q9H2A2; -.
DR BioMuta; ALDH8A1; -.
DR DMDM; 74752601; -.
DR jPOST; Q9H2A2; -.
DR MassIVE; Q9H2A2; -.
DR MaxQB; Q9H2A2; -.
DR PaxDb; Q9H2A2; -.
DR PeptideAtlas; Q9H2A2; -.
DR PRIDE; Q9H2A2; -.
DR ProteomicsDB; 80515; -. [Q9H2A2-1]
DR ProteomicsDB; 80516; -. [Q9H2A2-2]
DR ProteomicsDB; 80517; -. [Q9H2A2-3]
DR ProteomicsDB; 80518; -. [Q9H2A2-4]
DR Antibodypedia; 19736; 126 antibodies from 21 providers.
DR DNASU; 64577; -.
DR Ensembl; ENST00000265605.7; ENSP00000265605.2; ENSG00000118514.14. [Q9H2A2-1]
DR Ensembl; ENST00000349305.8; ENSP00000325473.4; ENSG00000118514.14. [Q9H2A2-3]
DR Ensembl; ENST00000367845.6; ENSP00000356819.2; ENSG00000118514.14. [Q9H2A2-2]
DR Ensembl; ENST00000367847.2; ENSP00000356821.2; ENSG00000118514.14. [Q9H2A2-4]
DR GeneID; 64577; -.
DR KEGG; hsa:64577; -.
DR MANE-Select; ENST00000265605.7; ENSP00000265605.2; NM_022568.4; NP_072090.1.
DR UCSC; uc003qew.3; human. [Q9H2A2-1]
DR CTD; 64577; -.
DR DisGeNET; 64577; -.
DR GeneCards; ALDH8A1; -.
DR HGNC; HGNC:15471; ALDH8A1.
DR HPA; ENSG00000118514; Group enriched (kidney, liver).
DR MIM; 606467; gene.
DR neXtProt; NX_Q9H2A2; -.
DR OpenTargets; ENSG00000118514; -.
DR PharmGKB; PA24705; -.
DR VEuPathDB; HostDB:ENSG00000118514; -.
DR eggNOG; KOG2450; Eukaryota.
DR GeneTree; ENSGT00940000156799; -.
DR HOGENOM; CLU_005391_0_0_1; -.
DR InParanoid; Q9H2A2; -.
DR OMA; PMPIAAW; -.
DR OrthoDB; 899961at2759; -.
DR PhylomeDB; Q9H2A2; -.
DR TreeFam; TF314129; -.
DR BioCyc; MetaCyc:ENSG00000118514-MON; -.
DR BRENDA; 1.2.1.3; 2681.
DR PathwayCommons; Q9H2A2; -.
DR Reactome; R-HSA-5365859; RA biosynthesis pathway.
DR SABIO-RK; Q9H2A2; -.
DR SignaLink; Q9H2A2; -.
DR UniPathway; UPA00334; -.
DR BioGRID-ORCS; 64577; 13 hits in 1068 CRISPR screens.
DR ChiTaRS; ALDH8A1; human.
DR GenomeRNAi; 64577; -.
DR Pharos; Q9H2A2; Tbio.
DR PRO; PR:Q9H2A2; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9H2A2; protein.
DR Bgee; ENSG00000118514; Expressed in nephron tubule and 131 other tissues.
DR ExpressionAtlas; Q9H2A2; baseline and differential.
DR Genevisible; Q9H2A2; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0047102; F:aminomuconate-semialdehyde dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0001758; F:retinal dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0042904; P:9-cis-retinoic acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0097053; P:L-kynurenine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0042574; P:retinal metabolic process; IDA:UniProtKB.
DR GO; GO:0042573; P:retinoic acid metabolic 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_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 Alternative splicing; Cytoplasm; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..487
FT /note="2-aminomuconic semialdehyde dehydrogenase"
FT /id="PRO_0000312954"
FT ACT_SITE 253
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 287
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 209..215
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT SITE 155
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 148..197
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043279"
FT VAR_SEQ 148..160
FT /note="AGLISPWNLPLYL -> VPGYTCRTCRFVT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039759"
FT VAR_SEQ 161..487
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039760"
FT VAR_SEQ 284..337
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11007799,
FT ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_029972"
FT VARIANT 402
FT /note="F -> S (in dbSNP:rs2294315)"
FT /id="VAR_037618"
FT MUTAGEN 109
FT /note="R->A: About 65-fold loss of catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:29703752"
FT MUTAGEN 155
FT /note="N->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:29703752"
FT MUTAGEN 451
FT /note="R->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:29703752"
FT CONFLICT 252
FT /note="L -> P (in Ref. 3; BAD96568)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 487 AA; 53401 MW; 3CC09F6A7CCC269F CRC64;
MAGTNALLML ENFIDGKFLP CSSYIDSYDP STGEVYCRVP NSGKDEIEAA VKAAREAFPS
WSSRSPQERS RVLNQVADLL EQSLEEFAQA ESKDQGKTLA LARTMDIPRS VQNFRFFASS
SLHHTSECTQ MDHLGCMHYT VRAPVGVAGL ISPWNLPLYL LTWKIAPAMA AGNTVIAKPS
ELTSVTAWML CKLLDKAGVP PGVVNIVFGT GPRVGEALVS HPEVPLISFT GSQPTAERIT
QLSAPHCKKL SLELGGKNPA IIFEDANLDE CIPATVRSSF ANQGEICLCT SRIFVQKSIY
SEFLKRFVEA TRKWKVGIPS DPLVSIGALI SKAHLEKVRS YVKRALAEGA QIWCGEGVDK
LSLPARNQAG YFMLPTVITD IKDESCCMTE EIFGPVTCVV PFDSEEEVIE RANNVKYGLA
ATVWSSNVGR VHRVAKKLQS GLVWTNCWLI RELNLPFGGM KSSGIGREGA KDSYDFFTEI
KTITVKH
