AL1A3_MOUSE
ID AL1A3_MOUSE Reviewed; 512 AA.
AC Q9JHW9; Q9EQP7; Q9JI72;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Aldehyde dehydrogenase family 1 member A3;
DE EC=1.2.1.36 {ECO:0000269|PubMed:11013254, ECO:0000269|PubMed:11044606};
DE AltName: Full=Aldehyde dehydrogenase 6 {ECO:0000303|PubMed:11013254};
DE AltName: Full=Retinaldehyde dehydrogenase 3;
DE Short=RALDH-3 {ECO:0000303|PubMed:11044606};
DE Short=RalDH3 {ECO:0000303|PubMed:11025231};
GN Name=Aldh1a3; Synonyms=Aldh6, Raldh3;
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], AND TISSUE SPECIFICITY.
RC STRAIN=B6/D2;
RX PubMed=10906479; DOI=10.1016/s0925-4773(00)00352-x;
RA Li H., Wagner E., McCaffery P., Smith D., Andreadis A., Drager U.C.;
RT "A retinoic acid synthesizing enzyme in ventral retina and telencephalon of
RT the embryonic mouse.";
RL Mech. Dev. 95:283-289(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6 X 129/SvJ; TISSUE=Kidney;
RX PubMed=11025231; DOI=10.1016/s0925-4773(00)00434-2;
RA Mic F.A., Molotkov A., Fan X., Cuenca A.E., Duester G.;
RT "RALDH3, a retinaldehyde dehydrogenase that generates retinoic acid, is
RT expressed in the ventral retina, otic vesicle and olfactory pit during
RT mouse development.";
RL Mech. Dev. 97:227-230(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, CATALYTIC
RP ACTIVITY, AND PATHWAY.
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=11044606; DOI=10.1016/s0925-4773(00)00450-0;
RA Suzuki R., Shintani T., Sakuta H., Kato A., Ohkawara T., Osumi N., Noda M.;
RT "Identification of RALDH-3, a novel retinaldehyde dehydrogenase, expressed
RT in the ventral region of the retina.";
RL Mech. Dev. 98:37-50(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, CATALYTIC ACTIVITY, PATHWAY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=11013254; DOI=10.1074/jbc.m007376200;
RA Grun F., Hirose Y., Kawauchi S., Ogura T., Umesono K.;
RT "Aldehyde dehydrogenase 6, a cytosolic retinaldehyde dehydrogenase
RT prominently expressed in sensory neuroepithelia during development.";
RL J. Biol. Chem. 275:41210-41218(2000).
RN [5]
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 [6]
RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND PATHWAY.
RX PubMed=14623956; DOI=10.1073/pnas.2336223100;
RA Dupe V., Matt N., Garnier J.M., Chambon P., Mark M., Ghyselinck N.B.;
RT "A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase
RT type 3 is prevented by maternal retinoic acid treatment.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:14036-14041(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
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 [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=23536097; DOI=10.1523/jneurosci.4618-12.2013;
RA Romand R., Krezel W., Beraneck M., Cammas L., Fraulob V., Messaddeq N.,
RA Kessler P., Hashino E., Dolle P.;
RT "Retinoic acid deficiency impairs the vestibular function.";
RL J. Neurosci. 33:5856-5866(2013).
CC -!- FUNCTION: NAD-dependent aldehyde dehydrogenase that catalyzes the
CC formation of retinoic acid (PubMed:11044606, PubMed:11013254,
CC PubMed:14623956). Has high activity with all-trans retinal, and has
CC much lower in vitro activity with acetaldehyde (By similarity).
CC Required for the biosynthesis of normal levels of retinoic acid in the
CC embryonic ocular and nasal regions; retinoic acid is required for
CC normal embryonic development of the eye and the nasal region
CC (PubMed:14623956). {ECO:0000250|UniProtKB:P47895,
CC ECO:0000269|PubMed:11013254, ECO:0000269|PubMed:11044606,
CC ECO:0000269|PubMed:14623956}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinal + H2O + NAD(+) = all-trans-retinoate + 2
CC H(+) + NADH; Xref=Rhea:RHEA:42080, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17898, ChEBI:CHEBI:35291,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.36;
CC Evidence={ECO:0000269|PubMed:11013254, ECO:0000269|PubMed:11044606};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.33 uM for all-trans retinal {ECO:0000269|PubMed:11013254};
CC Vmax=58 nmol/min/mg enzyme for all-trans retinal
CC {ECO:0000269|PubMed:11013254};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000269|PubMed:11013254, ECO:0000269|PubMed:11044606,
CC ECO:0000269|PubMed:14623956}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P47895}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11013254}.
CC -!- TISSUE SPECIFICITY: Detected in embryonic head (at protein level)
CC (PubMed:14623956). Ventral retina. {ECO:0000269|PubMed:10906479,
CC ECO:0000269|PubMed:11013254, ECO:0000269|PubMed:11025231,
CC ECO:0000269|PubMed:11044606, ECO:0000269|PubMed:14623956}.
CC -!- DEVELOPMENTAL STAGE: In mouse embryos, RALDH3 expression is first
CC noticed in the ventral optic eminence at 8.75 dpc, then in the optic
CC vesicle/cup, otic vesicle and olfactory placode/pit from 9.5 dpc to
CC 11.5 dpc. {ECO:0000269|PubMed:11025231}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate, but all die within 10 hours after birth (PubMed:14623956,
CC PubMed:23536097). Lethality is due to respiratory distress, caused by
CC choanal atresia, i.e. the lack of communication between the nasal and
CC oral cavities. Mutant embryos at 11.5 dpc lack detectable retinoic acid
CC in the ventral retina, nasal epithelium and in the nasolacrimal groove.
CC At 14.5 dpc mutant embryos display shortening of the ventral retina
CC associated with lens rotation and persistence of the retrolenticular
CC membrane, indicative of retinoic acid deficiency. Still, at 18.5 dpc
CC the ventral retina appears normal. Embryos at 18.5 dpc lack Harderian
CC glands, and display multiple malformations in the nasal region,
CC including choanal atresia, lack of maxillary sinuses and nasolacrimal
CC ducts (PubMed:14623956). Oral gavage of pregnant females with retinoic
CC acid prevents choanal atresia and other malformations of the nasal
CC region (PubMed:14623956, PubMed:23536097). Females that were fed
CC retinoic acid give birth to pups with malformations of the inner ear
CC vestibular organ, causing repetitive circling behavior with head
CC tilting (PubMed:23536097). Likewise, mice display impaired ability in
CC crossing a beam without slipping and an impaired ability to swim
CC (PubMed:23536097). {ECO:0000269|PubMed:14623956,
CC ECO:0000269|PubMed:23536097}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AF253409; AAF67736.1; -; mRNA.
DR EMBL; AF280404; AAF86980.1; -; mRNA.
DR EMBL; AF246711; AAG38488.1; -; mRNA.
DR EMBL; AF152359; AAG33935.1; -; mRNA.
DR EMBL; BC058277; AAH58277.1; -; mRNA.
DR CCDS; CCDS21345.1; -.
DR RefSeq; NP_444310.3; NM_053080.3.
DR AlphaFoldDB; Q9JHW9; -.
DR SMR; Q9JHW9; -.
DR BioGRID; 208193; 1.
DR STRING; 10090.ENSMUSP00000015278; -.
DR iPTMnet; Q9JHW9; -.
DR PhosphoSitePlus; Q9JHW9; -.
DR jPOST; Q9JHW9; -.
DR MaxQB; Q9JHW9; -.
DR PaxDb; Q9JHW9; -.
DR PRIDE; Q9JHW9; -.
DR ProteomicsDB; 285806; -.
DR Antibodypedia; 43944; 235 antibodies from 31 providers.
DR DNASU; 56847; -.
DR Ensembl; ENSMUST00000015278; ENSMUSP00000015278; ENSMUSG00000015134.
DR GeneID; 56847; -.
DR KEGG; mmu:56847; -.
DR UCSC; uc009hhi.2; mouse.
DR CTD; 220; -.
DR MGI; MGI:1861722; Aldh1a3.
DR VEuPathDB; HostDB:ENSMUSG00000015134; -.
DR eggNOG; KOG2450; Eukaryota.
DR GeneTree; ENSGT00940000158815; -.
DR HOGENOM; CLU_005391_0_1_1; -.
DR InParanoid; Q9JHW9; -.
DR OMA; NDDLGEV; -.
DR OrthoDB; 153834at2759; -.
DR PhylomeDB; Q9JHW9; -.
DR TreeFam; TF300455; -.
DR BRENDA; 1.2.1.36; 3474.
DR BRENDA; 1.2.1.5; 3474.
DR Reactome; R-MMU-5365859; RA biosynthesis pathway.
DR SABIO-RK; Q9JHW9; -.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 56847; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Aldh1a3; mouse.
DR PRO; PR:Q9JHW9; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9JHW9; protein.
DR Bgee; ENSMUSG00000015134; Expressed in optic fissure and 220 other tissues.
DR ExpressionAtlas; Q9JHW9; baseline and differential.
DR Genevisible; Q9JHW9; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; TAS:MGI.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IDA:MGI.
DR GO; GO:0004030; F:aldehyde dehydrogenase [NAD(P)+] activity; IDA:MGI.
DR GO; GO:0070403; F:NAD+ binding; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0001758; F:retinal dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0070324; F:thyroid hormone binding; IPI:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0031076; P:embryonic camera-type eye development; IMP:UniProtKB.
DR GO; GO:0048048; P:embryonic eye morphogenesis; IMP:MGI.
DR GO; GO:0060324; P:face development; IGI:MGI.
DR GO; GO:0070384; P:Harderian gland development; IMP:UniProtKB.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IMP:MGI.
DR GO; GO:0043584; P:nose development; IMP:UniProtKB.
DR GO; GO:0021768; P:nucleus accumbens development; IMP:MGI.
DR GO; GO:0060166; P:olfactory pit development; IMP:MGI.
DR GO; GO:0002072; P:optic cup morphogenesis involved in camera-type eye development; IGI:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
DR GO; GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; ISO:MGI.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0042574; P:retinal metabolic process; ISO:MGI.
DR GO; GO:0002138; P:retinoic acid biosynthetic process; IDA:MGI.
DR GO; GO:0042573; P:retinoic acid metabolic process; IMP:MGI.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0060013; P:righting reflex; IMP:MGI.
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 InterPro; IPR012394; Aldehyde_DH_NAD(P).
DR Pfam; PF00171; Aldedh; 1.
DR PIRSF; PIRSF036492; ALDH; 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; Cytoplasm; Lipid metabolism; NAD; Oxidoreductase;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P47895"
FT CHAIN 2..512
FT /note="Aldehyde dehydrogenase family 1 member A3"
FT /id="PRO_0000056479"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 280
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 314
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007,
FT ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 204
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P47895"
FT BINDING 207
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P47895"
FT BINDING 257..262
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P47895"
FT BINDING 361
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P47895"
FT BINDING 411
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P47895"
FT SITE 181
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P47895"
FT CONFLICT 91
FT /note="L -> V (in Ref. 1; AAF67736)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="Q -> R (in Ref. 4; AAG33935)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="V -> E (in Ref. 1; AAF67736)"
FT /evidence="ECO:0000305"
FT CONFLICT 341
FT /note="R -> S (in Ref. 4; AAG33935)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="I -> R (in Ref. 1; AAF67736)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 512 AA; 56157 MW; 5BBC6DEE41E58CFE CRC64;
MATTNGAVEN GQPDGKPPAL PRPIRNLEVK FTKIFINNDW HESKSGRKFA TYNPSTLEKI
CEVEEGDKPD VDKAVEAAQA AFQRGSPWRR LDALSRGQLL HQLADLVERD RAILATLETM
DTGKPFLHAF FVDLEGCIKT FRYFAGWADK IQGRTIPTDD NVVCFTRHEP IGVCGAITPW
NFPLLMLAWK LAPALCCGNT VVLKPAEQTP LTALYLASLI KEVGFPPGVV NIVPGFGPTV
GAAISSHPQI NKIAFTGSTE VGKLVREAAS RSNLKRVTLE LGGKNPCIVC ADADLDLAVE
CAHQGVFFNQ GQCCTAASRV FVEEQVYGEF VRRSVEFAKK RPVGDPFDAK TEQGPQIDQK
QFDKILELIE SGKKEGAKLE CGGSAMEDRG LFIKPTVFSD VTDNMRIAKE EIFGPVQPIL
KFKNLEEVIK RANSTDYGLT AAVFTKNLDK ALKLAAALES GTVWINCYNA FYAQAPFGGF
KMSGNGRELG EYALAEYTEV KTVTIKLEEK NP
