AL1A2_RAT
ID AL1A2_RAT Reviewed; 518 AA.
AC Q63639; Q4FZY8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Retinal dehydrogenase 2;
DE Short=RALDH 2;
DE Short=RalDH2;
DE EC=1.2.1.36 {ECO:0000269|PubMed:8663198};
DE AltName: Full=Aldehyde dehydrogenase family 1 member A2;
DE AltName: Full=Retinaldehyde-specific dehydrogenase type 2;
DE Short=RALDH(II) {ECO:0000303|PubMed:8663198};
GN Name=Aldh1a2; Synonyms=Raldh2;
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 [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-518, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC TISSUE=Testis;
RX PubMed=8663198; DOI=10.1074/jbc.271.27.16288;
RA Wang X., Penzes P., Napoli J.L.;
RT "Cloning of a cDNA encoding an aldehyde dehydrogenase and its expression in
RT Escherichia coli. Recognition of retinal as substrate.";
RL J. Biol. Chem. 271:16288-16293(1996).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 20-518 IN COMPLEX WITH NAD.
RX PubMed=10320326; DOI=10.1021/bi9900471;
RA Lamb A.L., Newcomer M.E.;
RT "The structure of retinal dehydrogenase type II at 2.7 A resolution:
RT implications for retinal specificity.";
RL Biochemistry 38:6003-6011(1999).
CC -!- FUNCTION: Converts retinaldehyde to retinoic acid. Recognizes as
CC substrates free retinal and cellular retinol-binding protein-bound
CC retinal. Can metabolize octanal and decanal, but has only very low
CC activity with benzaldehyde, acetaldehyde and propanal. Displays
CC complete lack of activity with citral. {ECO:0000269|PubMed:8663198}.
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:0000269|PubMed:8663198};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.7 uM for free retinal {ECO:0000269|PubMed:8663198};
CC KM=0.4 uM for all-trans-retinal {ECO:0000269|PubMed:8663198};
CC KM=70 uM for NADP {ECO:0000269|PubMed:8663198};
CC KM=400 uM for NADP {ECO:0000269|PubMed:8663198};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000269|PubMed:8663198}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:O94788}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Found in testis and less abundantly in lung, brain,
CC heart, liver and kidney.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC52637.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BC098910; AAH98910.1; -; mRNA.
DR EMBL; U60063; AAC52637.1; ALT_INIT; mRNA.
DR RefSeq; NP_446348.2; NM_053896.2.
DR PDB; 1BI9; X-ray; 2.70 A; A/B/C/D=20-518.
DR PDBsum; 1BI9; -.
DR AlphaFoldDB; Q63639; -.
DR SMR; Q63639; -.
DR STRING; 10116.ENSRNOP00000021757; -.
DR jPOST; Q63639; -.
DR PaxDb; Q63639; -.
DR Ensembl; ENSRNOT00000079115; ENSRNOP00000073203; ENSRNOG00000055049.
DR GeneID; 116676; -.
DR KEGG; rno:116676; -.
DR UCSC; RGD:620250; rat.
DR CTD; 8854; -.
DR RGD; 620250; Aldh1a2.
DR eggNOG; KOG2450; Eukaryota.
DR GeneTree; ENSGT00940000158898; -.
DR HOGENOM; CLU_005391_0_1_1; -.
DR InParanoid; Q63639; -.
DR OMA; RKAFEKW; -.
DR OrthoDB; 153834at2759; -.
DR PhylomeDB; Q63639; -.
DR TreeFam; TF300455; -.
DR BRENDA; 1.2.1.36; 5301.
DR Reactome; R-RNO-5365859; RA biosynthesis pathway.
DR UniPathway; UPA00912; -.
DR EvolutionaryTrace; Q63639; -.
DR PRO; PR:Q63639; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000055049; Expressed in testis and 19 other tissues.
DR Genevisible; Q63639; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; ISO:RGD.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0016918; F:retinal binding; IDA:RGD.
DR GO; GO:0001758; F:retinal dehydrogenase activity; IDA:RGD.
DR GO; GO:0042904; P:9-cis-retinoic acid biosynthetic process; ISO:RGD.
DR GO; GO:0009952; P:anterior/posterior pattern specification; ISO:RGD.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0043010; P:camera-type eye development; ISO:RGD.
DR GO; GO:0048738; P:cardiac muscle tissue development; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:RGD.
DR GO; GO:0009855; P:determination of bilateral symmetry; ISO:RGD.
DR GO; GO:0031076; P:embryonic camera-type eye development; ISO:RGD.
DR GO; GO:0048566; P:embryonic digestive tract development; ISO:RGD.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; ISO:RGD.
DR GO; GO:0030326; P:embryonic limb morphogenesis; ISO:RGD.
DR GO; GO:0060324; P:face development; ISO:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0003007; P:heart morphogenesis; ISO:RGD.
DR GO; GO:0030902; P:hindbrain development; ISO:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0007494; P:midgut development; IEP:RGD.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0014032; P:neural crest cell development; ISO:RGD.
DR GO; GO:0021915; P:neural tube development; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR GO; GO:0031016; P:pancreas 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:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0009954; P:proximal/distal pattern formation; ISO:RGD.
DR GO; GO:0001936; P:regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:1905562; P:regulation of vascular endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; ISO:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0033189; P:response to vitamin A; 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; IDA:RGD.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; ISO:RGD.
DR GO; GO:0090242; P:retinoic acid receptor signaling pathway involved in somitogenesis; ISO:RGD.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0035799; P:ureter maturation; ISO:RGD.
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 3D-structure; Cytoplasm; Lipid metabolism; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..518
FT /note="Retinal dehydrogenase 2"
FT /id="PRO_0000056424"
FT ACT_SITE 286
FT /note="Proton acceptor"
FT ACT_SITE 320
FT /note="Nucleophile"
FT BINDING 184..186
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10320326,
FT ECO:0007744|PDB:1BI9"
FT BINDING 210..213
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10320326,
FT ECO:0007744|PDB:1BI9"
FT BINDING 264..266
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O94788"
FT BINDING 366..370
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O94788"
FT BINDING 417
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O94788"
FT SITE 187
FT /note="Transition state stabilizer"
FT MOD_RES 168
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O94788"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94788"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:1BI9"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 74..88
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 99..115
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 117..128
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 132..137
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 139..151
FT /evidence="ECO:0007829|PDB:1BI9"
FT TURN 152..155
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 159..162
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 165..176
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 179..183
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 189..202
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 217..229
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 235..238
FT /evidence="ECO:0007829|PDB:1BI9"
FT TURN 243..245
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 246..252
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 265..277
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 282..286
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 301..313
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 314..317
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 326..329
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 330..346
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 365..379
FT /evidence="ECO:0007829|PDB:1BI9"
FT TURN 380..382
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 384..387
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 393..396
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 402..406
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 412..415
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 420..428
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 431..439
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 445..450
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 454..463
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 467..472
FT /evidence="ECO:0007829|PDB:1BI9"
FT HELIX 499..501
FT /evidence="ECO:0007829|PDB:1BI9"
FT STRAND 504..512
FT /evidence="ECO:0007829|PDB:1BI9"
SQ SEQUENCE 518 AA; 56640 MW; 2BDDAABB0D2D066C CRC64;
MTSSEIAMPG EVKADPAALM ASLQLLPSPT PNLEIKYTKI FINNEWQNSE SGRVFPVCNP
ATGEQVCEVQ EADKVDIDKA VQAARLAFSL GSVWRRMDAS ERGRLLDKLA DLVERDRATL
ATMESLNGGK PFLQAFYIDL QGVIKTLRYY AGWADKIHGM TIPVDGDYFT FTRHEPIGVC
GQIIPWNFPL LMFTWKIAPA LCCGNTVVIK PAEQTPLSAL YMGALIKEAG FPPGVVNILP
GYGPTAGAAI ASHIGIDKIA FTGSTEVGKL IQEAAGRSNL KRVTLELGGK SPNIIFADAD
LDYAVEQAHQ GVFFNQGQCC TAGSRIFVEE SIYEEFVKRS VERAKRRIVG SPFDPTTEQG
PQIDKKQYNK ILELIQSGVA EGAKLECGGK GLGRKGFFIE PTVFSNVTDD MRIAKEEIFG
PVQEILRFKT MDEVIERANN SDFGLVAAVF TNDINKALMV SSAMQAGTVW INCYNALNAQ
SPFGGFKMSG NGREMGEFGL REYSEVKTVT VKIPQKNS
