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-
CC       trans-13,14-dihydroretinoate, respectively (Probable). High specificity
CC       for 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-
CC         trans-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}.
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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
//