RDH16_MOUSE
ID RDH16_MOUSE Reviewed; 317 AA.
AC O54909;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Retinol dehydrogenase 16;
DE EC=1.1.1.105 {ECO:0000250|UniProtKB:O75452};
DE EC=1.1.1.209 {ECO:0000269|PubMed:9407098};
DE EC=1.1.1.315 {ECO:0000269|PubMed:9407098};
DE EC=1.1.1.53 {ECO:0000250|UniProtKB:O75452};
DE AltName: Full=Cis-retinol androgen dehydrogenase 1 {ECO:0000303|PubMed:9407098};
GN Name=Rdh16 {ECO:0000312|MGI:MGI:1201375};
GN Synonyms=Crad {ECO:0000303|PubMed:9407098},
GN Crad1 {ECO:0000303|PubMed:16223484}, Rdh1 {ECO:0000303|PubMed:15355969},
GN Rdh6 {ECO:0000312|MGI:MGI:1201375};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX PubMed=9407098; DOI=10.1074/jbc.272.52.33125;
RA Chai X., Zhai Y., Napoli J.L.;
RT "cDNA cloning and characterization of a cis-retinol/3alpha-hydroxysterol
RT short-chain dehydrogenase.";
RL J. Biol. Chem. 272:33125-33131(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [5]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=11279029; DOI=10.1074/jbc.m100215200;
RA Tryggvason K., Romert A., Eriksson U.;
RT "Biosynthesis of 9-cis-retinoic acid in vivo. The roles of different
RT retinol dehydrogenases and a structure-activity analysis of microsomal
RT retinol dehydrogenases.";
RL J. Biol. Chem. 276:19253-19258(2001).
RN [6]
RP SUBCELLULAR LOCATION, CAUTION, TOPOLOGY, AND NOT GLYCOSYLATED.
RX PubMed=15355969; DOI=10.1074/jbc.m409051200;
RA Zhang M., Hu P., Napoli J.L.;
RT "Elements in the N-terminal signaling sequence that determine cytosolic
RT topology of short-chain dehydrogenases/reductases. Studies with retinol
RT dehydrogenase type 1 and cis-retinol/androgen dehydrogenase type 1.";
RL J. Biol. Chem. 279:51482-51489(2004).
RN [7]
RP SUBCELLULAR LOCATION, SUBUNIT, DOMAIN, CATALYTIC ACTIVITY, TOPOLOGY, AND
RP CAUTION.
RX PubMed=16223484; DOI=10.1016/j.yexcr.2005.07.032;
RA Liden M., Tryggvason K., Eriksson U.;
RT "The C-terminal region of cis-retinol/androgen dehydrogenase 1 (CRAD1)
RT confers ER localization and in vivo enzymatic function.";
RL Exp. Cell Res. 311:205-217(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Oxidoreductase with a preference for NAD. Oxidizes all-trans-
CC retinol, 9-cis-retinol, 11-cis-retinol and 13-cis-retinol to the
CC corresponding aldehydes. Has higher activity towards CRBP-bound retinol
CC than with free retinol. Oxidizes 3-alpha-hydroxysteroids. Oxidizes
CC androstanediol and androsterone to dihydrotestosterone and
CC androstanedione. Can also catalyze the reverse reaction.
CC {ECO:0000250|UniProtKB:O75452}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol--[retinol-binding protein] + NAD(+) = all-
CC trans-retinal--[retinol-binding protein] + H(+) + NADH;
CC Xref=Rhea:RHEA:48488, Rhea:RHEA-COMP:14428, Rhea:RHEA-COMP:14430,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:83228;
CC EC=1.1.1.105; Evidence={ECO:0000250|UniProtKB:O75452};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-cis-retinol + NAD(+) = 9-cis-retinal + H(+) + NADH;
CC Xref=Rhea:RHEA:42052, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273;
CC Evidence={ECO:0000269|PubMed:16223484, ECO:0000269|PubMed:9407098};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-cis-retinol + NAD(+) = 11-cis-retinal + H(+) + NADH;
CC Xref=Rhea:RHEA:42060, ChEBI:CHEBI:15378, ChEBI:CHEBI:16066,
CC ChEBI:CHEBI:16302, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.315; Evidence={ECO:0000269|PubMed:9407098};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13-cis-retinol + NAD(+) = 13-cis-retinal + H(+) + NADH;
CC Xref=Rhea:RHEA:42056, ChEBI:CHEBI:15378, ChEBI:CHEBI:45479,
CC ChEBI:CHEBI:45487, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000250|UniProtKB:O75452};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:20381,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16032,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.209;
CC Evidence={ECO:0000269|PubMed:9407098};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42004,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.53;
CC Evidence={ECO:0000269|PubMed:9407098};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.2 uM for 3alpha-hydroxy-5alpha-androstan-17-one (androsterone)
CC {ECO:0000269|PubMed:9407098};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000250|UniProtKB:O75452}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16223484}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11279029, ECO:0000269|PubMed:15355969,
CC ECO:0000269|PubMed:16223484}; Single-pass membrane protein
CC {ECO:0000255}. Microsome membrane {ECO:0000269|PubMed:9407098}.
CC -!- DOMAIN: The C-terminal region plays a crucial role in controlling the
CC activity of RDH16 and its required for endoplasmic reticulum (ER)
CC retention. {ECO:0000269|PubMed:11279029, ECO:0000269|PubMed:16223484}.
CC -!- PTM: Not glycosylated. {ECO:0000269|PubMed:15355969}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- CAUTION: Membrane topology is controversial (PubMed:16223484,
CC PubMed:15355969). Membrane topology structure with endoplasmic
CC reticulum lumen orientation of the catalytic domains while the C-
CC terminus is in the cytosol have been suggested (PubMed:16223484,
CC PubMed:11279029). Others investigators have argued for a reverse
CC orientation, with a membrane-embedded N-terminal domain but no C-
CC terminal transmembrane segment, and a cytosolic orientation of the
CC catalytic domain (PubMed:15355969). These contradictory results are
CC probably because of differences in the assay systems.
CC {ECO:0000269|PubMed:11279029, ECO:0000269|PubMed:15355969,
CC ECO:0000269|PubMed:16223484, 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; AF030513; AAB97166.1; -; mRNA.
DR EMBL; AC131690; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466578; EDL24525.1; -; Genomic_DNA.
DR EMBL; BC089612; AAH89612.1; -; mRNA.
DR CCDS; CCDS24252.1; -.
DR RefSeq; NP_033066.1; NM_009040.3.
DR RefSeq; XP_006513452.1; XM_006513389.2.
DR AlphaFoldDB; O54909; -.
DR SMR; O54909; -.
DR STRING; 10090.ENSMUSP00000071573; -.
DR SwissLipids; SLP:000000799; -.
DR iPTMnet; O54909; -.
DR PhosphoSitePlus; O54909; -.
DR jPOST; O54909; -.
DR MaxQB; O54909; -.
DR PaxDb; O54909; -.
DR PeptideAtlas; O54909; -.
DR PRIDE; O54909; -.
DR ProteomicsDB; 336748; -.
DR DNASU; 19683; -.
DR Ensembl; ENSMUST00000071646; ENSMUSP00000071573; ENSMUSG00000069456.
DR GeneID; 19683; -.
DR KEGG; mmu:19683; -.
DR UCSC; uc007hkq.2; mouse.
DR CTD; 8608; -.
DR MGI; MGI:1201375; Rdh16.
DR VEuPathDB; HostDB:ENSMUSG00000069456; -.
DR eggNOG; KOG1610; Eukaryota.
DR GeneTree; ENSGT00940000154118; -.
DR HOGENOM; CLU_010194_2_0_1; -.
DR InParanoid; O54909; -.
DR OMA; LRWYWER; -.
DR OrthoDB; 942985at2759; -.
DR PhylomeDB; O54909; -.
DR TreeFam; TF325617; -.
DR BRENDA; 1.1.1.315; 3474.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 19683; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Rdh16; mouse.
DR PRO; PR:O54909; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; O54909; protein.
DR Bgee; ENSMUSG00000069456; Expressed in right kidney and 48 other tissues.
DR ExpressionAtlas; O54909; baseline and differential.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0031301; C:integral component of organelle membrane; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0047044; F:androstan-3-alpha,17-beta-diol dehydrogenase activity; ISO:MGI.
DR GO; GO:0047023; F:androsterone dehydrogenase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0042904; P:9-cis-retinoic acid biosynthetic process; IDA:MGI.
DR GO; GO:1900054; P:positive regulation of retinoic acid biosynthetic process; ISO:MGI.
DR GO; GO:0042573; P:retinoic acid metabolic process; ISO:MGI.
DR GO; GO:0001523; P:retinoid metabolic process; IDA:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; ISO:MGI.
DR GO; GO:0008202; P:steroid metabolic process; IDA:UniProtKB.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid metabolism; Membrane; Microsome; NAD;
KW Oxidoreductase; Reference proteome; Steroid metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..317
FT /note="Retinol dehydrogenase 16"
FT /id="PRO_0000446674"
FT TRANSMEM 289..309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 176
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O75452,
FT ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 33..57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
SQ SEQUENCE 317 AA; 35744 MW; B3D82F3F1D5D57C8 CRC64;
MWLYLVALVG LWTLLRFFRV RQVVSHLQDK YVFITGCDSG FGTLLARQLD RRGMRVLAAC
LTEKGAEELR NKTSDRLETV ILDVTKTESI VTATQWVKEH VGNRGLWGLV NNAGISTPSG
PNEWMKKQDF AHVLDVNLLG MIEVTLSMLP LVRKARGRVV NVSSVMGRVS LFGGGYCISK
YGVEAFSDSL RRELSYFGVK VAIIEPGFFL TGVTSSARLC SNTQMLWDQT SSEIREIYGE
KYLASYLKRL NKLDKRCNKD LSGVTDCMEH ALTACHPRTR YSAGWDAKLF YLPLSYLPTF
LVDALLYWTS LKPEKAL
