RDH8_HUMAN
ID RDH8_HUMAN Reviewed; 311 AA.
AC Q9NYR8; Q9H838;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Retinol dehydrogenase 8;
DE EC=1.1.1.300 {ECO:0000250|UniProtKB:Q9N126};
DE AltName: Full=Photoreceptor outer segment all-trans retinol dehydrogenase;
DE AltName: Full=Short chain dehydrogenase/reductase family 28C member 2;
GN Name=RDH8; Synonyms=PRRDH, SDR28C2;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=10753906; DOI=10.1074/jbc.275.15.11034;
RA Rattner A., Smallwood P.M., Nathans J.;
RT "Identification and characterization of all-trans-retinol dehydrogenase
RT from photoreceptor outer segments, the visual cycle enzyme that reduces
RT all-trans-retinal to all-trans-retinol.";
RL J. Biol. Chem. 275:11034-11043(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
CC -!- FUNCTION: Retinol dehydrogenase with a clear preference for NADP.
CC Converts all-trans-retinal to all-trans-retinol. May play a role in the
CC regeneration of visual pigment at high light intensity (By similarity).
CC {ECO:0000250|UniProtKB:Q9N126}.
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:Q9N126};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:10753906}; Multi-
CC pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in photoreceptor outer segments in the
CC retina (at protein level). {ECO:0000269|PubMed:10753906}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14782.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF229845; AAF63160.1; -; mRNA.
DR EMBL; AK024022; BAB14782.1; ALT_FRAME; mRNA.
DR CCDS; CCDS12223.2; -.
DR RefSeq; NP_056540.2; NM_015725.2.
DR AlphaFoldDB; Q9NYR8; -.
DR SMR; Q9NYR8; -.
DR BioGRID; 119119; 40.
DR STRING; 9606.ENSP00000466058; -.
DR DrugBank; DB00162; Vitamin A.
DR iPTMnet; Q9NYR8; -.
DR PhosphoSitePlus; Q9NYR8; -.
DR BioMuta; RDH8; -.
DR DMDM; 74753074; -.
DR MassIVE; Q9NYR8; -.
DR PaxDb; Q9NYR8; -.
DR PeptideAtlas; Q9NYR8; -.
DR PRIDE; Q9NYR8; -.
DR ProteomicsDB; 83268; -.
DR TopDownProteomics; Q9NYR8; -.
DR Antibodypedia; 25134; 17 antibodies from 7 providers.
DR DNASU; 50700; -.
DR Ensembl; ENST00000591589.3; ENSP00000466058.2; ENSG00000080511.5.
DR GeneID; 50700; -.
DR KEGG; hsa:50700; -.
DR MANE-Select; ENST00000591589.3; ENSP00000466058.2; NM_015725.4; NP_056540.3.
DR CTD; 50700; -.
DR DisGeNET; 50700; -.
DR GeneCards; RDH8; -.
DR HGNC; HGNC:14423; RDH8.
DR HPA; ENSG00000080511; Tissue enriched (retina).
DR MIM; 608575; gene.
DR neXtProt; NX_Q9NYR8; -.
DR OpenTargets; ENSG00000080511; -.
DR PharmGKB; PA34309; -.
DR VEuPathDB; HostDB:ENSG00000080511; -.
DR eggNOG; KOG1205; Eukaryota.
DR GeneTree; ENSGT00940000155412; -.
DR InParanoid; Q9NYR8; -.
DR OrthoDB; 1313182at2759; -.
DR PhylomeDB; Q9NYR8; -.
DR TreeFam; TF105451; -.
DR BioCyc; MetaCyc:HS01358-MON; -.
DR BRENDA; 1.1.1.300; 2681.
DR PathwayCommons; Q9NYR8; -.
DR Reactome; R-HSA-2453902; The canonical retinoid cycle in rods (twilight vision).
DR BioGRID-ORCS; 50700; 16 hits in 1064 CRISPR screens.
DR ChiTaRS; RDH8; human.
DR GeneWiki; RDH8; -.
DR GenomeRNAi; 50700; -.
DR Pharos; Q9NYR8; Tbio.
DR PRO; PR:Q9NYR8; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NYR8; protein.
DR Bgee; ENSG00000080511; Expressed in sperm and 66 other tissues.
DR ExpressionAtlas; Q9NYR8; baseline and differential.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IEA:InterPro.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006703; P:estrogen biosynthetic process; IEA:InterPro.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0042572; P:retinol metabolic process; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; TAS:ProtInc.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR InterPro; IPR011348; 17beta_DH.
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 PIRSF; PIRSF000095; 17beta-HSD; 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 Lipid metabolism; Membrane; NADP; Oxidoreductase; Reference proteome;
KW Sensory transduction; Transmembrane; Transmembrane helix; Vision.
FT CHAIN 1..311
FT /note="Retinol dehydrogenase 8"
FT /id="PRO_0000305972"
FT TRANSMEM 86..106
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 9..18
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q12634"
FT BINDING 142
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT VARIANT 136
FT /note="H -> Q (in dbSNP:rs1122206)"
FT /id="VAR_035232"
FT VARIANT 202
FT /note="M -> T (in dbSNP:rs1644731)"
FT /id="VAR_035233"
SQ SEQUENCE 311 AA; 33755 MW; D62416D1F0377ECE CRC64;
MAAAPRTVLI SGCSSGIGLE LAVQLAHDPK KRYQVVATMR DLGKKETLEA AAGEALGQTL
TVAQLDVCSD ESVAQCLSCI QGEVDVLVNN AGMGLVGPLE GLSLAAMQNV FDTNFFGAVR
LVKAVLPGMK RRRQGHIVVI SSVMGLQGVI FNDVYAASKF ALEGFFESLA IQLLQFNIFI
SLVEPGPVVT EFEGKLLAQV SMAEFPGTDP ETLHYFRDLY LPASRKLFCS VGQNPQDVVQ
AIVNVISSTR PPLRRQTNIR YSPLTTLKTV DSSGSLYVRT THRLLFRCPR LLNLGLQCLS
CGCLPTRVRP R
