AL8A1_MOUSE
ID AL8A1_MOUSE Reviewed; 487 AA.
AC Q8BH00; Q91WS6;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=2-aminomuconic semialdehyde dehydrogenase;
DE EC=1.2.1.32 {ECO:0000250|UniProtKB:Q9H2A2};
DE AltName: Full=Aldehyde dehydrogenase family 8 member A1;
DE AltName: Full=Retinal dehydrogenase 4;
GN Name=Aldh8a1; Synonyms=Raldh4;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=12519776; DOI=10.1074/jbc.m211417200;
RA Lin M., Zhang M., Abraham M., Smith S.M., Napoli J.L.;
RT "Mouse retinal dehydrogenase 4 (RALDH4), molecular cloning, cellular
RT expression, and activity in 9-cis-retinoic acid biosynthesis in intact
RT cells.";
RL J. Biol. Chem. 278:9856-9861(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver tumor, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-145.
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
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).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidation of 2-aminomuconic
CC semialdehyde of the kynurenine metabolic pathway in L-tryptophan
CC degradation. {ECO:0000250|UniProtKB:Q9H2A2}.
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:0000250|UniProtKB:Q9H2A2};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.3 uM for 9-cis-retinal {ECO:0000269|PubMed:12519776};
CC Vmax=3.4 nmol/min/mg enzyme {ECO:0000269|PubMed:12519776};
CC Note=Activity was measured with total soluble protein.;
CC -!- PATHWAY: Amino-acid degradation; L-kynurenine degradation.
CC {ECO:0000250|UniProtKB:Q9H2A2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12519776}.
CC -!- TISSUE SPECIFICITY: Detected in hepatocytes and in proximal and distal
CC convoluted tubules in kidney cortex (at protein level). Highly
CC expressed in adult liver and in kidney cortex. First detected in
CC embryonic liver after 15 days of development.
CC {ECO:0000269|PubMed:12519776}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AF510322; AAO64246.1; -; mRNA.
DR EMBL; AK050298; BAC34173.1; -; mRNA.
DR EMBL; AK143752; BAE25524.1; -; mRNA.
DR EMBL; BC013511; AAH13511.1; -; mRNA.
DR EMBL; BC038493; AAH38493.1; -; mRNA.
DR CCDS; CCDS23723.1; -.
DR RefSeq; NP_848828.1; NM_178713.4.
DR AlphaFoldDB; Q8BH00; -.
DR SMR; Q8BH00; -.
DR STRING; 10090.ENSMUSP00000038878; -.
DR iPTMnet; Q8BH00; -.
DR PhosphoSitePlus; Q8BH00; -.
DR SwissPalm; Q8BH00; -.
DR EPD; Q8BH00; -.
DR jPOST; Q8BH00; -.
DR MaxQB; Q8BH00; -.
DR PaxDb; Q8BH00; -.
DR PeptideAtlas; Q8BH00; -.
DR PRIDE; Q8BH00; -.
DR ProteomicsDB; 296169; -.
DR Antibodypedia; 19736; 126 antibodies from 21 providers.
DR DNASU; 237320; -.
DR Ensembl; ENSMUST00000042699; ENSMUSP00000038878; ENSMUSG00000037542.
DR GeneID; 237320; -.
DR KEGG; mmu:237320; -.
DR UCSC; uc007eoq.1; mouse.
DR CTD; 64577; -.
DR MGI; MGI:2653900; Aldh8a1.
DR VEuPathDB; HostDB:ENSMUSG00000037542; -.
DR eggNOG; KOG2450; Eukaryota.
DR GeneTree; ENSGT00940000156799; -.
DR HOGENOM; CLU_005391_0_2_1; -.
DR InParanoid; Q8BH00; -.
DR OMA; PMPIAAW; -.
DR OrthoDB; 899961at2759; -.
DR PhylomeDB; Q8BH00; -.
DR TreeFam; TF314129; -.
DR BRENDA; 1.2.1.3; 3474.
DR Reactome; R-MMU-5365859; RA biosynthesis pathway.
DR UniPathway; UPA00334; -.
DR BioGRID-ORCS; 237320; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Aldh8a1; mouse.
DR PRO; PR:Q8BH00; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8BH00; protein.
DR Bgee; ENSMUSG00000037542; Expressed in right kidney and 33 other tissues.
DR Genevisible; Q8BH00; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:MGI.
DR GO; GO:0042904; P:9-cis-retinoic acid biosynthetic process; IDA:MGI.
DR GO; GO:0097053; P:L-kynurenine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0042574; P:retinal metabolic process; ISS:UniProtKB.
DR GO; GO:0042573; P:retinoic acid metabolic process; 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 Cytoplasm; NAD; Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..487
FT /note="2-aminomuconic semialdehyde dehydrogenase"
FT /id="PRO_0000312955"
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 231..236
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT SITE 155
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H2A2"
FT VARIANT 145
FT /note="V -> G (in strain: FVB/N)"
FT /evidence="ECO:0000269|PubMed:15489334"
SQ SEQUENCE 487 AA; 53664 MW; 5E205A495BD61ED7 CRC64;
MAGKRELLML ENFIGGKFLP CNSYIDSYDP STGEVYCKVP NSGKEEIEAA VEAAREAFPA
WSSRSPQERS LVLNRLADVL EQSLEELAQA ESKDQGKTLT LARTMDIPRS VLNFRFFASS
NLHHVSECTQ MSHLGCMHYT VRTPVGIAGL ISPWNLPLYL LTWKIAPAIA AGNTVIAKPS
EMTSVTAWMF CKLLDKAGVP PGVINIVFGT GPRVGEALVS HPEVPLISFT GSQPTAERIT
QLSAPHCKKL SLELGGKNPA IIFEDANLEE CIPATVRSSF ANQGEICLCT SRIFVQRSIY
SEFLKRFVEA TRKWKVGVPS DPSANMGALI SKAHLEKVRS YVLKAQTEGA RILCGEGVDQ
LSLPLRNQAG YFMLPTVITD IKDESRCMTE EIFGPVTCVV PFDSEEEVIT RANSVRYGLA
ATVWSKDVGR IHRVAKKLQS GLVWTNCWLI RELNLPFGGM KSSGIGREGA KDSYDFFTEI
KTITIKY
