ID AL1A2_HUMAN Reviewed; 518 AA. AC O94788; B3KY52; B4DZR2; F5H2Y9; H0YM00; Q2PJS6; Q8NHQ4; Q9UBR8; Q9UFY0; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 3. DT 24-JAN-2024, entry version 200. DE RecName: Full=Retinal dehydrogenase 2; DE Short=RALDH 2; DE Short=RalDH2 {ECO:0000303|PubMed:9819382}; DE EC=1.2.1.36 {ECO:0000269|PubMed:29240402}; DE AltName: Full=Aldehyde dehydrogenase family 1 member A2; DE Short=ALDH1A2 {ECO:0000303|PubMed:22075477}; DE AltName: Full=Retinaldehyde-specific dehydrogenase type 2; DE Short=RALDH(II); GN Name=ALDH1A2; Synonyms=RALDH2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4), AND VARIANT ILE-348. RX PubMed=9819382; DOI=10.1128/mcb.18.12.6939; RA Ono Y., Fukuhara N., Yoshie O.; RT "TAL1 and LIM-only proteins synergistically induce retinaldehyde RT dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting RT as cofactors for GATA3."; RL Mol. Cell. Biol. 18:6939-6950(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT RP ILE-348. RC TISSUE=Testis, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-50; VAL-110; ILE-348 RP AND LYS-436. RG NIEHS SNPs program; RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 302-518 (ISOFORMS 1/2), AND RP VARIANT ILE-348. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP FUNCTION. RX PubMed=22075477; DOI=10.1095/biolreprod.111.096610; RA Griswold M.D., Hogarth C.A., Bowles J., Koopman P.; RT "Initiating meiosis: the case for retinoic acid."; RL Biol. Reprod. 86:35-35(2012). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-168 AND SER-351, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] RP INVOLVEMENT IN DIH4, VARIANTS DIH4 LYS-182; HIS-347; THR-383 AND TYR-461, RP CHARACTERIZATION OF VARIANTS DIH4 LYS-182; HIS-347; THR-383 AND TYR-461, RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=33565183; DOI=10.1002/humu.24179; RA Beecroft S.J., Ayala M., McGillivray G., Nanda V., Agolini E., Novelli A., RA Digilio M.C., Dotta A., Carrozzo R., Clayton J., Gaffney L., McLean C.A., RA Ng J., Laing N.G., Matteson P., Millonig J., Ravenscroft G.; RT "Biallelic hypomorphic variants in ALDH1A2 cause a novel lethal human RT multiple congenital anomaly syndrome encompassing diaphragmatic, pulmonary, RT and cardiovascular defects."; RL Hum. Mutat. 42:506-519(2021). RN [11] {ECO:0007744|PDB:4X2Q} RP X-RAY CRYSTALLOGRAPHY (2.94 ANGSTROMS) OF 21-518 IN COMPLEX WITH NAD. RA Goldstein A.S., Paik J., Moreb J., Haenisch M., Le Trong I., Stenkamp R.E., RA Petrie A.G., Smith N., Mallochowski W.P., Amory J.K.; RT "Synthesis and in vitro testing of bisdichloroacetyldiamine analogs for use RT as a reversible male contraceptive."; RL Submitted (NOV-2014) to the PDB data bank. RN [12] {ECO:0007744|PDB:6ALJ, ECO:0007744|PDB:6B5G, ECO:0007744|PDB:6B5H, ECO:0007744|PDB:6B5I} RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 26-518 IN COMPLEXES WITH NAD AND RP SYNTHETIC INHIBITORS, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, ACTIVE SITE, RP AND PATHWAY. RX PubMed=29240402; DOI=10.1021/acschembio.7b00685; RA Chen Y., Zhu J.Y., Hong K.H., Mikles D.C., Georg G.I., Goldstein A.S., RA Amory J.K., Schonbrunn E.; RT "Structural Basis of ALDH1A2 Inhibition by Irreversible and Reversible RT Small Molecule Inhibitors."; RL ACS Chem. Biol. 13:582-590(2018). RN [13] RP VARIANT DIH4 HIS-347, AND CHARACTERIZATION OF VARIANT DIH4 HIS-347. RX PubMed=36263470; DOI=10.1002/ajmg.a.62991; RA Leon E., Nde C., Ray R.S., Preciado D., Zohn I.E.; RT "ALDH1A2-related disorder: A new genetic syndrome due to alteration of the RT retinoic acid pathway."; RL Am. J. Med. Genet. A 191:90-99(2023). 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 (PubMed:29240402, CC PubMed:33565183). Retinoate signaling is critical for the CC transcriptional control of many genes, for instance it is crucial for CC initiation of meiosis in both male and female (PubMed:33565183) CC (Probable). Recognizes retinal as substrate, both in its free form and CC when bound to cellular retinol-binding protein (By similarity). Can CC metabolize octanal and decanal, but has only very low activity with CC benzaldehyde, acetaldehyde and propanal (By similarity). Displays CC complete lack of activity with citral (By similarity). CC {ECO:0000250|UniProtKB:Q63639, ECO:0000269|PubMed:29240402, CC ECO:0000269|PubMed:33565183, ECO:0000305|PubMed:22075477}. 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:29240402, ECO:0000269|PubMed:33565183}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16178; CC Evidence={ECO:0000269|PubMed:29240402, ECO:0000269|PubMed:33565183}; 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:Q62148}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42081; CC Evidence={ECO:0000250|UniProtKB:Q62148}; 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:Q62148}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75120; CC Evidence={ECO:0000250|UniProtKB:Q62148}; CC -!- PATHWAY: Cofactor metabolism; retinol metabolism. CC {ECO:0000269|PubMed:29240402}. CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:29240402}. CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=O94788-1; Sequence=Displayed; CC Name=2; CC IsoId=O94788-2; Sequence=VSP_017363; CC Name=3; CC IsoId=O94788-3; Sequence=VSP_044496; CC Name=4; CC IsoId=O94788-4; Sequence=VSP_047259; CC -!- DISEASE: Diaphragmatic hernia 4, with cardiovascular defects (DIH4) CC [MIM:620025]: An autosomal recessive form of congenital diaphragmatic CC hernia, a posterolateral defect of the diaphragm, generally located on CC the left side, that permits the herniation of abdominal viscera into CC the thorax. The lungs are hypoplastic and have abnormal vessels that CC cause respiratory insufficiency and persistent pulmonary hypertension CC with high mortality. About one third of cases have cardiovascular CC malformations and lesser proportions have skeletal, neural, CC genitourinary, gastrointestinal or other defects. CC {ECO:0000269|PubMed:33565183, ECO:0000269|PubMed:36263470}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/aldh1a2/"; 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; AB015226; BAA34785.1; -; mRNA. DR EMBL; AB015227; BAA34786.1; -; mRNA. DR EMBL; AB015228; BAA34787.1; -; mRNA. DR EMBL; AK128709; BAG54714.1; -; mRNA. DR EMBL; AK303057; BAG64174.1; -; mRNA. DR EMBL; DQ322171; ABC40749.1; -; Genomic_DNA. DR EMBL; AC012653; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC018904; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC025431; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC066616; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC084781; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC030589; AAH30589.1; -; mRNA. DR EMBL; AL110299; CAB53740.2; -; mRNA. DR CCDS; CCDS10163.1; -. [O94788-1] DR CCDS; CCDS10164.1; -. [O94788-2] DR CCDS; CCDS45266.1; -. [O94788-4] DR CCDS; CCDS55968.1; -. [O94788-3] DR PIR; T14799; T14799. DR RefSeq; NP_001193826.1; NM_001206897.1. [O94788-3] DR RefSeq; NP_003879.2; NM_003888.3. [O94788-1] DR RefSeq; NP_733797.1; NM_170696.2. [O94788-2] DR RefSeq; NP_733798.1; NM_170697.2. [O94788-4] DR PDB; 4X2Q; X-ray; 2.94 A; A/B/C/D=21-518. DR PDB; 6ALJ; X-ray; 1.89 A; A/B/C/D=26-518. DR PDB; 6B5G; X-ray; 2.20 A; A/B/C/D=26-518. DR PDB; 6B5H; X-ray; 2.30 A; A/B/C/D=26-518. DR PDB; 6B5I; X-ray; 2.60 A; A/B/C/D=26-518. DR PDBsum; 4X2Q; -. DR PDBsum; 6ALJ; -. DR PDBsum; 6B5G; -. DR PDBsum; 6B5H; -. DR PDBsum; 6B5I; -. DR AlphaFoldDB; O94788; -. DR SMR; O94788; -. DR BioGRID; 114379; 79. DR IntAct; O94788; 8. DR STRING; 9606.ENSP00000249750; -. DR BindingDB; O94788; -. DR ChEMBL; CHEMBL3112384; -. DR DrugBank; DB00157; NADH. DR DrugBank; DB00755; Tretinoin. DR DrugBank; DB00162; Vitamin A. DR DrugCentral; O94788; -. DR GlyGen; O94788; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O94788; -. DR PhosphoSitePlus; O94788; -. DR BioMuta; ALDH1A2; -. DR EPD; O94788; -. DR jPOST; O94788; -. DR MassIVE; O94788; -. DR MaxQB; O94788; -. DR PaxDb; 9606-ENSP00000249750; -. DR PeptideAtlas; O94788; -. DR ProteomicsDB; 26115; -. DR ProteomicsDB; 40109; -. DR ProteomicsDB; 50442; -. [O94788-1] DR ProteomicsDB; 50443; -. [O94788-2] DR Pumba; O94788; -. DR Antibodypedia; 2127; 419 antibodies from 32 providers. DR DNASU; 8854; -. DR Ensembl; ENST00000249750.9; ENSP00000249750.4; ENSG00000128918.15. [O94788-1] DR Ensembl; ENST00000347587.7; ENSP00000309623.3; ENSG00000128918.15. [O94788-2] DR Ensembl; ENST00000537372.5; ENSP00000438296.1; ENSG00000128918.15. [O94788-3] DR Ensembl; ENST00000559517.5; ENSP00000453408.1; ENSG00000128918.15. [O94788-4] DR GeneID; 8854; -. DR KEGG; hsa:8854; -. DR MANE-Select; ENST00000249750.9; ENSP00000249750.4; NM_003888.4; NP_003879.2. DR UCSC; uc002aew.4; human. [O94788-1] DR AGR; HGNC:15472; -. DR CTD; 8854; -. DR DisGeNET; 8854; -. DR GeneCards; ALDH1A2; -. DR HGNC; HGNC:15472; ALDH1A2. DR HPA; ENSG00000128918; Tissue enhanced (endometrium, fallopian tube). DR MalaCards; ALDH1A2; -. DR MIM; 603687; gene. DR MIM; 620025; phenotype. DR neXtProt; NX_O94788; -. DR OpenTargets; ENSG00000128918; -. DR PharmGKB; PA24693; -. DR VEuPathDB; HostDB:ENSG00000128918; -. DR eggNOG; KOG2450; Eukaryota. DR GeneTree; ENSGT00940000158898; -. DR HOGENOM; CLU_005391_0_0_1; -. DR InParanoid; O94788; -. DR OMA; WSNTFNK; -. DR OrthoDB; 2291791at2759; -. DR PhylomeDB; O94788; -. DR TreeFam; TF300455; -. DR BioCyc; MetaCyc:HS05232-MONOMER; -. DR BRENDA; 1.2.1.36; 2681. DR PathwayCommons; O94788; -. DR Reactome; R-HSA-5365859; RA biosynthesis pathway. DR SignaLink; O94788; -. DR SIGNOR; O94788; -. DR UniPathway; UPA00912; -. DR BioGRID-ORCS; 8854; 9 hits in 1163 CRISPR screens. DR ChiTaRS; ALDH1A2; human. DR GeneWiki; ALDH1A2; -. DR GenomeRNAi; 8854; -. DR Pharos; O94788; Tchem. DR PRO; PR:O94788; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; O94788; Protein. DR Bgee; ENSG00000128918; Expressed in germinal epithelium of ovary and 154 other cell types or tissues. DR ExpressionAtlas; O94788; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0004028; F:3-chloroallyl aldehyde dehydrogenase activity; ISS:UniProtKB. DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IBA:GO_Central. DR GO; GO:0016918; F:retinal binding; ISS:UniProtKB. DR GO; GO:0001758; F:retinal dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0042904; P:9-cis-retinoic acid biosynthetic process; IEA:Ensembl. DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl. DR GO; GO:0048738; P:cardiac muscle tissue development; IEA:Ensembl. DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl. DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl. DR GO; GO:0009855; P:determination of bilateral symmetry; IEA:Ensembl. DR GO; GO:0031076; P:embryonic camera-type eye development; IEA:Ensembl. DR GO; GO:0048566; P:embryonic digestive tract development; IEA:Ensembl. DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl. DR GO; GO:0060324; P:face development; IEA:Ensembl. DR GO; GO:0003007; P:heart morphogenesis; IEA:Ensembl. DR GO; GO:0030902; P:hindbrain development; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; IEA:Ensembl. DR GO; GO:0001889; P:liver development; IEA:Ensembl. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0007494; P:midgut development; IEA:Ensembl. DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0014032; P:neural crest cell development; IEA:Ensembl. DR GO; GO:0021915; P:neural tube development; IMP:UniProtKB. DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl. DR GO; GO:0031016; P:pancreas development; IEA:Ensembl. DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl. DR GO; GO:1905562; P:regulation of vascular endothelial cell proliferation; IEA:Ensembl. DR GO; GO:0034097; P:response to cytokine; IDA:UniProtKB. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0032526; P:response to retinoic acid; IMP:UniProtKB. DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl. DR GO; GO:0042574; P:retinal metabolic process; IEA:Ensembl. DR GO; GO:0002138; P:retinoic acid biosynthetic process; IDA:UniProtKB. DR GO; GO:0042573; P:retinoic acid metabolic process; IMP:UniProtKB. DR GO; GO:0090242; P:retinoic acid receptor signaling pathway involved in somitogenesis; IEA:Ensembl. DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0035799; P:ureter maturation; IEA:Ensembl. DR GO; GO:0006776; P:vitamin A metabolic process; NAS:UniProtKB. 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; IPR029510; Ald_DH_CS_GLU. DR InterPro; IPR016162; Ald_DH_N. DR InterPro; IPR015590; Aldehyde_DH_dom. DR PANTHER; PTHR11699; ALDEHYDE DEHYDROGENASE-RELATED; 1. DR PANTHER; PTHR11699:SF102; RETINAL DEHYDROGENASE 2; 1. DR Pfam; PF00171; Aldedh; 1. DR SUPFAM; SSF53720; ALDH-like; 1. DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1. DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1. DR Genevisible; O94788; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; KW Lipid metabolism; NAD; Oxidoreductase; Phosphoprotein; Reference proteome. FT CHAIN 1..518 FT /note="Retinal dehydrogenase 2" FT /id="PRO_0000056422" FT ACT_SITE 286 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007, FT ECO:0000255|PROSITE-ProRule:PRU10008" FT ACT_SITE 320 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007, FT ECO:0000255|PROSITE-ProRule:PRU10008, FT ECO:0000269|PubMed:29240402" FT BINDING 184..186 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:29240402, FT ECO:0007744|PDB:4X2Q, ECO:0007744|PDB:6ALJ, FT ECO:0007744|PDB:6B5G, ECO:0007744|PDB:6B5H" FT BINDING 210..213 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:29240402, FT ECO:0007744|PDB:4X2Q, ECO:0007744|PDB:6ALJ, FT ECO:0007744|PDB:6B5G, ECO:0007744|PDB:6B5H" FT BINDING 264..266 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:29240402, FT ECO:0007744|PDB:6ALJ, ECO:0007744|PDB:6B5G, FT ECO:0007744|PDB:6B5H" FT BINDING 366..370 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:29240402, FT ECO:0007744|PDB:6ALJ, ECO:0007744|PDB:6B5G, FT ECO:0007744|PDB:6B5H" FT BINDING 417 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:29240402, FT ECO:0007744|PDB:6ALJ, ECO:0007744|PDB:6B5G, FT ECO:0007744|PDB:6B5H" FT SITE 187 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250" FT MOD_RES 168 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 351 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..96 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:9819382" FT /id="VSP_047259" FT VAR_SEQ 1..39 FT /note="MTSSKIEMPGEVKADPAALMASLHLLPSPTPNLEIKYTK -> MKNQCETVW FT LKSPIKLKL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044496" FT VAR_SEQ 229..266 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_017363" FT VARIANT 50 FT /note="E -> G (in dbSNP:rs34266719)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025439" FT VARIANT 110 FT /note="A -> V (in dbSNP:rs35365164)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025440" FT VARIANT 182 FT /note="Q -> K (in DIH4; decreased retinoic acid FT biosynthetic process)" FT /evidence="ECO:0000269|PubMed:33565183" FT /id="VAR_087721" FT VARIANT 347 FT /note="R -> H (in DIH4; decreased expression; FT dbSNP:rs141245344)" FT /evidence="ECO:0000269|PubMed:33565183, FT ECO:0000269|PubMed:36263470" FT /id="VAR_087722" FT VARIANT 348 FT /note="V -> I (in dbSNP:rs4646626)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:17974005, ECO:0000269|PubMed:9819382, FT ECO:0000269|Ref.3" FT /id="VAR_025441" FT VARIANT 383 FT /note="A -> T (in DIH4; uncertain significance; FT dbSNP:rs749124508)" FT /evidence="ECO:0000269|PubMed:33565183" FT /id="VAR_087723" FT VARIANT 436 FT /note="E -> K (in dbSNP:rs34744827)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025442" FT VARIANT 461 FT /note="S -> Y (in DIH4; decreased retinoic acid FT biosynthetic process)" FT /evidence="ECO:0000269|PubMed:33565183" FT /id="VAR_087724" FT CONFLICT 231 FT /note="F -> L (in Ref. 2; BAG64174)" FT /evidence="ECO:0000305" FT STRAND 39..42 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 45..47 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 54..58 FT /evidence="ECO:0007829|PDB:6ALJ" FT TURN 60..62 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 65..70 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 74..87 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 93..96 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 99..115 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 117..128 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 132..137 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 139..151 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 154..156 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 159..162 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 165..176 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 178..183 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 186..188 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 189..202 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 206..210 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 213..215 FT /evidence="ECO:0007829|PDB:6B5I" FT HELIX 217..229 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 235..238 FT /evidence="ECO:0007829|PDB:6ALJ" FT TURN 243..245 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 246..251 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 258..263 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 265..277 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 282..286 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 292..295 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 301..313 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 314..317 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 325..329 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 330..346 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 365..380 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 384..387 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 393..396 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 402..406 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 412..415 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 420..428 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 431..439 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 441..450 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 454..463 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 466..472 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 479..481 FT /evidence="ECO:0007829|PDB:6B5I" FT STRAND 490..492 FT /evidence="ECO:0007829|PDB:6ALJ" FT HELIX 498..503 FT /evidence="ECO:0007829|PDB:6ALJ" FT STRAND 504..512 FT /evidence="ECO:0007829|PDB:6ALJ" SQ SEQUENCE 518 AA; 56724 MW; AAEE7A886951373F CRC64; MTSSKIEMPG EVKADPAALM ASLHLLPSPT PNLEIKYTKI FINNEWQNSE SGRVFPVYNP ATGEQVCEVQ EADKADIDKA VQAARLAFSL GSVWRRMDAS ERGRLLDKLA DLVERDRAVL ATMESLNGGK PFLQAFYVDL QGVIKTFRYY AGWADKIHGM TIPVDGDYFT FTRHEPIGVC GQIIPWNFPL LMFAWKIAPA LCCGNTVVIK PAEQTPLSAL YMGALIKEAG FPPGVINILP GYGPTAGAAI ASHIGIDKIA FTGSTEVGKL IQEAAGRSNL KRVTLELGGK SPNIIFADAD LDYAVEQAHQ GVFFNQGQCC TAGSRIFVEE SIYEEFVRRS VERAKRRVVG SPFDPTTEQG PQIDKKQYNK ILELIQSGVA EGAKLECGGK GLGRKGFFIE PTVFSNVTDD MRIAKEEIFG PVQEILRFKT MDEVIERANN SDFGLVAAVF TNDINKALTV SSAMQAGTVW INCYNALNAQ SPFGGFKMSG NGREMGEFGL REYSEVKTVT VKIPQKNS //