RDH12_MOUSE
ID RDH12_MOUSE Reviewed; 316 AA.
AC Q8BYK4; Q91WA5; Q9D1Y4;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Retinol dehydrogenase 12;
DE EC=1.1.1.300 {ECO:0000250|UniProtKB:Q96NR8};
GN Name=Rdh12;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=12226107; DOI=10.1074/jbc.m208882200;
RA Haeseleer F., Jang G.-F., Imanishi Y., Driessen C.A.G.G., Matsumura M.,
RA Nelson P.S., Palczewski K.;
RT "Dual-substrate specificity short chain retinol dehydrogenases from the
RT vertebrate retina.";
RL J. Biol. Chem. 277:45537-45546(2002).
RN [4]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=17032653; DOI=10.1074/jbc.m608375200;
RA Maeda A., Maeda T., Imanishi Y., Sun W., Jastrzebska B., Hatala D.A.,
RA Winkens H.J., Hofmann K.P., Janssen J.J., Baehr W., Driessen C.A.,
RA Palczewski K.;
RT "Retinol dehydrogenase (RDH12) protects photoreceptors from light-induced
RT degeneration in mice.";
RL J. Biol. Chem. 281:37697-37704(2006).
RN [5]
RP FUNCTION.
RX PubMed=19686838; DOI=10.1016/j.freeradbiomed.2009.08.005;
RA Marchette L.D., Thompson D.A., Kravtsova M., Ngansop T.N., Mandal M.N.,
RA Kasus-Jacobi A.;
RT "Retinol dehydrogenase 12 detoxifies 4-hydroxynonenal in photoreceptor
RT cells.";
RL Free Radic. Biol. Med. 48:16-25(2010).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22621924; DOI=10.1074/jbc.m112.354514;
RA Chen C., Thompson D.A., Koutalos Y.;
RT "Reduction of all-trans-retinal in vertebrate rod photoreceptors requires
RT the combined action of RDH8 and RDH12.";
RL J. Biol. Chem. 287:24662-24670(2012).
CC -!- FUNCTION: Retinoids dehydrogenase/reductase with a clear preference for
CC NADP. Displays high activity towards 9-cis, 11-cis and all-trans-
CC retinal. Shows very weak activity toward 13-cis-retinol. Also exhibits
CC activity, albeit with lower affinity than for retinaldehydes, towards
CC lipid peroxidation products (C9 aldehydes) such as 4-hydroxynonenal and
CC trans-2-nonenal (By similarity). Plays an important function in
CC photoreceptor cells to detoxify 4-hydroxynonenal and potentially other
CC toxic aldehyde products resulting from lipid peroxidation
CC (PubMed:19686838, PubMed:22621924, PubMed:17032653). Has no
CC dehydrogenase activity towards steroids (By similarity).
CC {ECO:0000250|UniProtKB:Q96NR8, ECO:0000269|PubMed:17032653,
CC ECO:0000269|PubMed:19686838, ECO:0000269|PubMed:22621924}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol + NADP(+) = all-trans-retinal + H(+) +
CC NADPH; Xref=Rhea:RHEA:25033, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17898, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.300; Evidence={ECO:0000250|UniProtKB:Q96NR8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-cis-retinol + NADP(+) = 11-cis-retinal + H(+) + NADPH;
CC Xref=Rhea:RHEA:54912, ChEBI:CHEBI:15378, ChEBI:CHEBI:16066,
CC ChEBI:CHEBI:16302, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:Q96NR8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-cis-retinol + NADP(+) = 9-cis-retinal + H(+) + NADPH;
CC Xref=Rhea:RHEA:54916, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273;
CC Evidence={ECO:0000250|UniProtKB:Q96NR8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 4-hydroxynonen-1-ol + NADP(+) = a 4-hydroxynonenal + H(+) +
CC NADPH; Xref=Rhea:RHEA:58336, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142593, ChEBI:CHEBI:142606;
CC Evidence={ECO:0000250|UniProtKB:Q96NR8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-non-2-en-1-ol + NADP(+) = (E)-non-2-enal + H(+) + NADPH;
CC Xref=Rhea:RHEA:58332, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142592, ChEBI:CHEBI:142604;
CC Evidence={ECO:0000250|UniProtKB:Q96NR8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(Z)-non-6-en-1-ol + NADP(+) = (Z)-non-6-enal + H(+) + NADPH;
CC Xref=Rhea:RHEA:58328, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142591, ChEBI:CHEBI:142603;
CC Evidence={ECO:0000250|UniProtKB:Q96NR8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + nonan-1-ol = H(+) + NADPH + nonanal;
CC Xref=Rhea:RHEA:58380, ChEBI:CHEBI:15378, ChEBI:CHEBI:35986,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:84268;
CC Evidence={ECO:0000250|UniProtKB:Q96NR8};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000250|UniProtKB:Q96NR8}.
CC -!- TISSUE SPECIFICITY: Expressed in the inner segments of the
CC photoreceptor in retina. {ECO:0000269|PubMed:12226107,
CC ECO:0000269|PubMed:17032653}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are fertile and developed
CC normally. Deficient mice exhibit normal retinal function at 6 weeks,
CC but they show increased susceptibility to retinal cell apoptosis of
CC both cone and rod photoreceptors induced by high intensity illumination
CC (PubMed:17032653). All- trans-retinol production in inner and outer
CC segments of the photoreceptor is not affected in deficient mice
CC (PubMed:22621924). {ECO:0000269|PubMed:17032653,
CC ECO:0000269|PubMed:22621924}.
CC -!- MISCELLANEOUS: Shows clear specificity for the pro-S hydrogen on C4 of
CC NADPH and the pro-R hydrogen on C15 of retinols.
CC {ECO:0000250|UniProtKB:Q96NR8}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AK020927; BAB32258.1; -; mRNA.
DR EMBL; AK039233; BAC30288.1; -; mRNA.
DR EMBL; BC016204; AAH16204.1; -; mRNA.
DR CCDS; CCDS26009.1; -.
DR RefSeq; NP_001300900.1; NM_001313971.1.
DR RefSeq; NP_084293.1; NM_030017.4.
DR AlphaFoldDB; Q8BYK4; -.
DR SMR; Q8BYK4; -.
DR STRING; 10090.ENSMUSP00000021548; -.
DR PhosphoSitePlus; Q8BYK4; -.
DR SwissPalm; Q8BYK4; -.
DR jPOST; Q8BYK4; -.
DR MaxQB; Q8BYK4; -.
DR PaxDb; Q8BYK4; -.
DR PeptideAtlas; Q8BYK4; -.
DR PRIDE; Q8BYK4; -.
DR ProteomicsDB; 255139; -.
DR Antibodypedia; 24894; 103 antibodies from 19 providers.
DR DNASU; 77974; -.
DR Ensembl; ENSMUST00000021548; ENSMUSP00000021548; ENSMUSG00000021123.
DR GeneID; 77974; -.
DR KEGG; mmu:77974; -.
DR UCSC; uc007oac.1; mouse.
DR CTD; 145226; -.
DR MGI; MGI:1925224; Rdh12.
DR VEuPathDB; HostDB:ENSMUSG00000021123; -.
DR eggNOG; KOG1208; Eukaryota.
DR GeneTree; ENSGT00940000161505; -.
DR HOGENOM; CLU_010194_44_5_1; -.
DR InParanoid; Q8BYK4; -.
DR OMA; SDCKKTW; -.
DR OrthoDB; 1032903at2759; -.
DR PhylomeDB; Q8BYK4; -.
DR TreeFam; TF105429; -.
DR BRENDA; 1.1.1.300; 3474.
DR Reactome; R-MMU-2453902; The canonical retinoid cycle in rods (twilight vision).
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 77974; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Rdh12; mouse.
DR PRO; PR:Q8BYK4; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8BYK4; protein.
DR Bgee; ENSMUSG00000021123; Expressed in retinal neural layer and 93 other tissues.
DR ExpressionAtlas; Q8BYK4; baseline and differential.
DR Genevisible; Q8BYK4; MM.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:UniProtKB.
DR GO; GO:0102354; F:11-cis-retinol dehydrogenase activity; IEA:RHEA.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0110095; P:cellular detoxification of aldehyde; IDA:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; IDA:UniProtKB.
DR GO; GO:0007601; P:visual perception; IMP:UniProtKB.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW Lipid metabolism; NADP; Oxidoreductase; Reference proteome;
KW Sensory transduction; Vision.
FT CHAIN 1..316
FT /note="Retinol dehydrogenase 12"
FT /id="PRO_0000054767"
FT ACT_SITE 200
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 46..52
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 114..125
FT /note="Missing (in Ref. 2; AAH16204)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="H -> D (in Ref. 1; BAB32258)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 316 AA; 35292 MW; CF5745B6710A6148 CRC64;
MLFILVLLTS FLSILYLTAP SIRKFFAGGV CTTNVQIPGK VVVITGANTG IGKETARELA
RRGARVYIAC RDVLKGESAA SEIRADTKNS QVLVRKLDLS DTKSIRAFAE RFLAEEKKLH
ILINNAGVMM CPYSKTTDGF ETHFGVNHLG HFLLTYLLLE RLKESAPARV VNLSSIAHLI
GKIRFHDLQG QKRYCSAFAY GHSKLANLLF TRELAKRLQG TGVTAYAVHP GVVLSEITRN
SYLLCLLWRL FSPFFKSTSQ GAQTSLHCAL AEDLEPLSGK YFSDCKRMWV SSRARNKKTA
ERLWNVSCEL LGIQWE
