ID AL1A3_RAT Reviewed; 512 AA.
AC Q8K4D8;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 24-JAN-2024, entry version 125.
DE RecName: Full=Retinaldehyde dehydrogenase 3;
DE Short=RALDH-3;
DE Short=RalDH3 {ECO:0000303|PubMed:12390888};
DE EC=1.2.1.36 {ECO:0000250|UniProtKB:Q9JHW9};
DE AltName: Full=Aldehyde dehydrogenase 6 {ECO:0000303|PubMed:12390888};
DE AltName: Full=Aldehyde dehydrogenase family 1 member A3;
DE Short=Aldh1a3;
GN Name=Aldh1a3; Synonyms=Aldh6, Raldh3;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=Sprague-Dawley;
RX PubMed=12390888; DOI=10.1095/biolreprod.102.007021;
RA Rexer B.N., Ong D.E.;
RT "A novel short-chain alcohol dehydrogenase from rats with retinol
RT dehydrogenase activity, cyclically expressed in uterine epithelium.";
RL Biol. Reprod. 67:1555-1564(2002).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidation of aldehyde substrates,
CC such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their
CC corresponding carboxylic acids, all-trans-retinoate and all-trans-
CC 13,14-dihydroretinoate, respectively (Probable). High specificity for
CC all-trans-retinal as substrate, can also accept acetaldehyde as
CC substrate in vitro but with lower affinity (By similarity). Required
CC for the biosynthesis of normal levels of retinoate in the embryonic
CC ocular and nasal regions; a critical lipid in the embryonic development
CC of the eye and the nasal region (By similarity).
CC {ECO:0000250|UniProtKB:P47895, ECO:0000250|UniProtKB:Q9JHW9,
CC ECO:0000305|PubMed:12390888}.
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:0000250|UniProtKB:P47895};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42081;
CC Evidence={ECO:0000250|UniProtKB:P47895};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) + retinal = 2 H(+) + NADH + retinoate;
CC Xref=Rhea:RHEA:16177, ChEBI:CHEBI:15035, ChEBI:CHEBI:15036,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.36;
CC Evidence={ECO:0000250|UniProtKB:P47895};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16178;
CC Evidence={ECO:0000250|UniProtKB:P47895};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-13,14-dihydroretinal + H2O + NAD(+) = all-trans-
CC 13,14-dihydroretinoate + 2 H(+) + NADH; Xref=Rhea:RHEA:75119,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:194182, ChEBI:CHEBI:194183;
CC Evidence={ECO:0000250|UniProtKB:Q9JHW9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75120;
CC Evidence={ECO:0000250|UniProtKB:Q9JHW9};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000250|UniProtKB:P47895}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P47895}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9JHW9}.
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; AF434845; AAN03711.1; -; mRNA.
DR RefSeq; NP_695212.1; NM_153300.1.
DR AlphaFoldDB; Q8K4D8; -.
DR SMR; Q8K4D8; -.
DR STRING; 10116.ENSRNOP00000069212; -.
DR PhosphoSitePlus; Q8K4D8; -.
DR jPOST; Q8K4D8; -.
DR PaxDb; 10116-ENSRNOP00000045261; -.
DR GeneID; 266603; -.
DR KEGG; rno:266603; -.
DR UCSC; RGD:628662; rat.
DR AGR; RGD:628662; -.
DR CTD; 220; -.
DR RGD; 628662; Aldh1a3.
DR eggNOG; KOG2450; Eukaryota.
DR InParanoid; Q8K4D8; -.
DR OrthoDB; 2291791at2759; -.
DR PhylomeDB; Q8K4D8; -.
DR BRENDA; 1.2.1.36; 5301.
DR Reactome; R-RNO-5365859; RA biosynthesis pathway.
DR UniPathway; UPA00912; -.
DR PRO; PR:Q8K4D8; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; ISO:RGD.
DR GO; GO:0004030; F:aldehyde dehydrogenase [NAD(P)+] activity; IDA:RGD.
DR GO; GO:0070403; F:NAD+ binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0001758; F:retinal dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0070324; F:thyroid hormone binding; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0031076; P:embryonic camera-type eye development; ISO:RGD.
DR GO; GO:0048048; P:embryonic eye morphogenesis; ISO:RGD.
DR GO; GO:0060324; P:face development; ISO:RGD.
DR GO; GO:0070384; P:Harderian gland development; ISO:RGD.
DR GO; GO:0042472; P:inner ear morphogenesis; ISO:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR GO; GO:0043584; P:nose development; ISO:RGD.
DR GO; GO:0021768; P:nucleus accumbens development; ISO:RGD.
DR GO; GO:0060166; P:olfactory pit development; ISO:RGD.
DR GO; GO:0002072; P:optic cup morphogenesis involved in camera-type eye development; ISO:RGD.
DR GO; GO:0021983; P:pituitary gland development; IEP:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0042574; P:retinal metabolic process; ISO:RGD.
DR GO; GO:0002138; P:retinoic acid biosynthetic process; IMP:RGD.
DR GO; GO:0042573; P:retinoic acid metabolic process; ISO:RGD.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0060013; P:righting reflex; ISO:RGD.
DR CDD; cd07141; ALDH_F1AB_F2_RALDH1; 1.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR016163; Ald_DH_C.
DR InterPro; IPR016160; Ald_DH_CS_CYS.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR PANTHER; PTHR11699:SF209; ALDEHYDE DEHYDROGENASE FAMILY 1 MEMBER A3; 1.
DR PANTHER; PTHR11699; ALDEHYDE DEHYDROGENASE-RELATED; 1.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; ALDH-like; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
PE 2: Evidence at transcript 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="Retinaldehyde dehydrogenase 3"
FT /id="PRO_0000056480"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 280
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10008"
FT ACT_SITE 314
FT /note="Nucleophile"
FT /evidence="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"
SQ SEQUENCE 512 AA; 56171 MW; 2A818D7472F67A5E CRC64;
MATANGAVEN GQPDGKPPAL PRPIRNLEVK FTKIFINNDW HEPKSGRKFA TYNPSTLEKI
CEVEEGDKPD VDKAVEAAQA AFQRGSPWRR LDALSRGQLL HQLADLIERD RAILATLETM
DTGKPFLHAF FVDLEGCIKT FRYFAGWADK IQGRTIPTDD NVMCFTRHEP IGVCGAITPW
NFPLLMLAWK LAPALCCGNT VVLKPAEQTP LTALYLASLI KEVGFPPGVV NIVPGFGPTV
GAAISSHPQI NKIAFTGSTE VGKLVKEAAS RSNLKRVTLE LGGRNPCIVC ADADLDLAVE
CAHQGVFFNQ GQCCTAASRV FVEEQVYGEF VRRSVEFAKK RPVGDPFDAK TEQGPQIDQK
QFDKILELIE SGKKEGAKLE CGGSAMEDRG LFIKPTVFSD VTDNMRIAKE EIFGPVQPIL
KFKNLEEVIK RANSTDYGLT AAVFTKNLDK ALKLASALES GTVWVNCYNA FYAQAPFGGF
KMSGNGRELG EYALAEYTEV KTVTIKLDEK NP
//
