ID   AL3A2_RAT               Reviewed;         484 AA.
AC   P30839;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   24-JAN-2024, entry version 158.
DE   RecName: Full=Aldehyde dehydrogenase family 3 member A2;
DE            EC=1.2.1.3 {ECO:0000250|UniProtKB:P47740};
DE            EC=1.2.1.94 {ECO:0000250|UniProtKB:P51648};
DE   AltName: Full=Aldehyde dehydrogenase 4;
DE   AltName: Full=Fatty aldehyde dehydrogenase;
DE   AltName: Full=Microsomal aldehyde dehydrogenase;
DE            Short=msALDH;
GN   Name=Aldh3a2; Synonyms=Aldh4;
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], PROTEIN SEQUENCE OF 93-110; 236-255 AND
RP   408-427, SUBCELLULAR LOCATION, AND TOPOLOGY.
RC   TISSUE=Liver;
RX   PubMed=1717467; DOI=10.1016/s0021-9258(18)55028-6;
RA   Miyauchi K., Masaki R., Taketani S., Yamamoto A., Akayama M., Tashiro Y.;
RT   "Molecular cloning, sequencing, and expression of cDNA for rat liver
RT   microsomal aldehyde dehydrogenase.";
RL   J. Biol. Chem. 266:19536-19542(1991).
CC   -!- FUNCTION: Catalyzes the oxidation of medium and long-chain aliphatic
CC       aldehydes to fatty acids. Active on a variety of saturated and
CC       unsaturated aliphatic aldehydes between 6 and 24 carbons in length.
CC       Responsible for conversion of the sphingosine 1-phosphate (S1P)
CC       degradation product hexadecenal to hexadecenoic acid (By similarity).
CC       {ECO:0000250|UniProtKB:P51648}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH;
CC         Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; EC=1.2.1.3;
CC         Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a fatty aldehyde + H2O + NAD(+) = a fatty acid + 2 H(+) +
CC         NADH; Xref=Rhea:RHEA:49832, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:28868, ChEBI:CHEBI:35746, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E)-hexadecenal + H2O + NAD(+) = (E)-hexadec-2-enoate + 2
CC         H(+) + NADH; Xref=Rhea:RHEA:36135, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:17585, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945, ChEBI:CHEBI:72745;
CC         Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 H(+) + hexadecanoate + NADH = H2O + hexadecanal + NAD(+);
CC         Xref=Rhea:RHEA:33739, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:17600, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=22-oxodocosanoate + H2O + NAD(+) = docosanedioate + 2 H(+) +
CC         NADH; Xref=Rhea:RHEA:39015, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:76298,
CC         ChEBI:CHEBI:76299; Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2,6,10,14-tetramethylpentadecanal + H2O + NAD(+) = 2,6,10,14-
CC         tetramethylpentadecanoate + 2 H(+) + NADH; Xref=Rhea:RHEA:44016,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:49189,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:77268;
CC         Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NAD(+) + octadecanal = 2 H(+) + NADH + octadecanoate;
CC         Xref=Rhea:RHEA:44020, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17034, ChEBI:CHEBI:25629, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dodecanoate + 2 H(+) + NADH = dodecanal + H2O + NAD(+);
CC         Xref=Rhea:RHEA:44168, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:18262, ChEBI:CHEBI:27836, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=decanal + H2O + NAD(+) = decanoate + 2 H(+) + NADH;
CC         Xref=Rhea:RHEA:44104, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:27689, ChEBI:CHEBI:31457, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NAD(+) + tetradecanal = 2 H(+) + NADH + tetradecanoate;
CC         Xref=Rhea:RHEA:44172, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30807, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC         ChEBI:CHEBI:84067; Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NAD(+) + octanal = 2 H(+) + NADH + octanoate;
CC         Xref=Rhea:RHEA:44100, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17935, ChEBI:CHEBI:25646, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + heptanal + NAD(+) = 2 H(+) + heptanoate + NADH;
CC         Xref=Rhea:RHEA:44108, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:32362, ChEBI:CHEBI:34787, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E,6E)-farnesal + H2O + NAD(+) = (2E,6E)-farnesoate + 2 H(+)
CC         + NADH; Xref=Rhea:RHEA:24216, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15894, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC         ChEBI:CHEBI:83276; EC=1.2.1.94;
CC         Evidence={ECO:0000250|UniProtKB:P51648};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P51648}.
CC   -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:1717467}.
CC       Endoplasmic reticulum membrane {ECO:0000269|PubMed:1717467}; Single-
CC       pass membrane protein {ECO:0000305|PubMed:1717467}; Cytoplasmic side
CC       {ECO:0000269|PubMed:1717467}.
CC   -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:1717467}.
CC   -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC       {ECO:0000305}.
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DR   EMBL; M73714; AAA41555.1; -; mRNA.
DR   PIR; A41028; A41028.
DR   RefSeq; NP_113919.2; NM_031731.2.
DR   AlphaFoldDB; P30839; -.
DR   SMR; P30839; -.
DR   IntAct; P30839; 1.
DR   STRING; 10116.ENSRNOP00000070512; -.
DR   CarbonylDB; P30839; -.
DR   iPTMnet; P30839; -.
DR   PhosphoSitePlus; P30839; -.
DR   SwissPalm; P30839; -.
DR   jPOST; P30839; -.
DR   PaxDb; 10116-ENSRNOP00000061762; -.
DR   GeneID; 65183; -.
DR   KEGG; rno:65183; -.
DR   UCSC; RGD:61866; rat.
DR   AGR; RGD:61866; -.
DR   CTD; 224; -.
DR   RGD; 61866; Aldh3a2.
DR   eggNOG; KOG2456; Eukaryota.
DR   InParanoid; P30839; -.
DR   OrthoDB; 606537at2759; -.
DR   PhylomeDB; P30839; -.
DR   Reactome; R-RNO-389599; Alpha-oxidation of phytanate.
DR   Reactome; R-RNO-428157; Sphingolipid metabolism.
DR   Reactome; R-RNO-9603798; Class I peroxisomal membrane protein import.
DR   Reactome; R-RNO-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR   Reactome; R-RNO-9696270; RND2 GTPase cycle.
DR   Reactome; R-RNO-9696273; RND1 GTPase cycle.
DR   PRO; PR:P30839; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC-UCL.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:RGD.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:RGD.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; IDA:RGD.
DR   GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; ISO:RGD.
DR   GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC.
DR   GO; GO:0046577; F:long-chain-alcohol oxidase activity; ISO:RGD.
DR   GO; GO:0050061; F:long-chain-aldehyde dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0052814; F:medium-chain-aldehyde dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR   GO; GO:0006081; P:cellular aldehyde metabolic process; ISO:RGD.
DR   GO; GO:0007417; P:central nervous system development; ISO:RGD.
DR   GO; GO:0008544; P:epidermis development; ISO:RGD.
DR   GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0046292; P:formaldehyde metabolic process; IDA:RGD.
DR   GO; GO:0046458; P:hexadecanal metabolic process; ISS:UniProtKB.
DR   GO; GO:0007422; P:peripheral nervous system development; ISO:RGD.
DR   GO; GO:0033306; P:phytol metabolic process; ISO:RGD.
DR   GO; GO:0000302; P:response to reactive oxygen species; IDA:RGD.
DR   CDD; cd07132; ALDH_F3AB; 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   PANTHER; PTHR43570; ALDEHYDE DEHYDROGENASE; 1.
DR   PANTHER; PTHR43570:SF9; ALDEHYDE DEHYDROGENASE FAMILY 3 MEMBER A2; 1.
DR   Pfam; PF00171; Aldedh; 1.
DR   PIRSF; PIRSF036492; ALDH; 1.
DR   SUPFAM; SSF53720; ALDH-like; 1.
DR   PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR   PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Endoplasmic reticulum; Fatty acid metabolism;
KW   Lipid metabolism; Membrane; Microsome; NAD; Oxidoreductase; Phosphoprotein;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..484
FT                   /note="Aldehyde dehydrogenase family 3 member A2"
FT                   /id="PRO_0000056476"
FT   TOPO_DOM        1..463
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:1717467"
FT   TRANSMEM        464..484
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   MOTIF           481..484
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        207
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT   ACT_SITE        241
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10008"
FT   BINDING         185..190
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         293
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P51648"
SQ   SEQUENCE   484 AA;  54082 MW;  9F50CB34AB64C31D CRC64;
     MERQVQRLRQ TFRSGRSRPL RFRLQQLEAL RRMVQEREKD ILAAIAADLS KSELNAYSHE
     VITILGEIDF MLGNLPELAS ARPAKKNLLT MMDEAYVQPE PLGVVLIIGA WNYPFVLTLQ
     PLVGAIAAGN AAIVKPSELS ENTAKILAEL LPQYLDQDLY MIVNGGVEET TELLRQRFDH
     ILYTGNTAVG KIVMEAAAKH LTPVTLELGG KSPCYIDRDC DLDVACRRIT WGKYMNCGQT
     CIAPDYILCE ASSQDQIVQK IKDTVKDFYG ENVKASPDYE RIINLRHFKR IKSLLEGQKI
     AFGGETDEAT RYIAPTILTD VDPNSKVMQE EIFGPILPIV SVKNVEEAIN FINDREKPLA
     LYIFSHNNKL IKRVIDETSS GGVTGNDVIM HFTVNSLPFG GVGASGMGAY HGKYSFDTFS
     HQRPCLLKGL KGESVNKLRY PPNSESKVSW SKFFLLKQFN KGRLQLLLLV CLVAVAAVIV
     KDQL
//