RDH14_HUMAN
ID RDH14_HUMAN Reviewed; 336 AA.
AC Q9HBH5;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Retinol dehydrogenase 14 {ECO:0000305};
DE EC=1.1.1.300 {ECO:0000269|PubMed:12435598};
DE AltName: Full=Alcohol dehydrogenase PAN2 {ECO:0000303|PubMed:12435598};
DE AltName: Full=Short chain dehydrogenase/reductase family 7C member 4;
GN Name=RDH14; Synonyms=PAN2, SDR7C4; ORFNames=UNQ529/PRO1072;
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].
RC TISSUE=Lung;
RA Brereton P.S., Li K.X., Krozowski Z.S.;
RT "Pan2, a novel member of the SCAD superfamily.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell;
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 [4]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY,
RP FUNCTION, AND SUBSTRATE SPECIFICITY.
RX PubMed=12435598; DOI=10.1016/s0014-5793(02)03588-3;
RA Belyaeva O.V., Kedishvili N.Y.;
RT "Human pancreas protein 2 (PAN2) has a retinal reductase activity and is
RT ubiquitously expressed in human tissues.";
RL FEBS Lett. 531:489-493(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [6]
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Retinol dehydrogenase with a clear preference for NADP.
CC Displays high activity towards 9-cis, 11-cis and all-trans-retinol.
CC Shows a very weak activity towards 13-cis-retinol. Has no activity
CC towards steroid. {ECO:0000269|PubMed:12435598}.
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:0000269|PubMed:12435598};
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:0000269|PubMed:12435598};
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:Q9ERI6};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.32 uM for NADPH {ECO:0000269|PubMed:12435598};
CC KM=0.65 uM for NADP {ECO:0000269|PubMed:12435598};
CC KM=0.08 uM for all-trans-retinal {ECO:0000269|PubMed:12435598};
CC KM=0.4 uM for all-trans-retinol {ECO:0000269|PubMed:12435598};
CC KM=1060 uM for NADH {ECO:0000269|PubMed:12435598};
CC Vmax=27 nmol/min/mg enzyme with all-trans-retinal as substrate
CC {ECO:0000269|PubMed:12435598};
CC Vmax=31 nmol/min/mg enzyme with all-trans-retinol as substrate
CC {ECO:0000269|PubMed:12435598};
CC Note=Vmax is measured per mg microsomal protein.
CC {ECO:0000269|PubMed:12435598};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000269|PubMed:12435598}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:12435598}.
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:Q9ERI6}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AF237952; AAG12190.1; -; mRNA.
DR EMBL; AY358511; AAQ88875.1; -; mRNA.
DR EMBL; BC009830; AAH09830.1; -; mRNA.
DR CCDS; CCDS1693.1; -.
DR RefSeq; NP_065956.1; NM_020905.3.
DR AlphaFoldDB; Q9HBH5; -.
DR SMR; Q9HBH5; -.
DR BioGRID; 121698; 33.
DR IntAct; Q9HBH5; 16.
DR MINT; Q9HBH5; -.
DR STRING; 9606.ENSP00000370648; -.
DR DrugBank; DB00162; Vitamin A.
DR SwissLipids; SLP:000001788; -.
DR iPTMnet; Q9HBH5; -.
DR PhosphoSitePlus; Q9HBH5; -.
DR BioMuta; RDH14; -.
DR DMDM; 34395826; -.
DR EPD; Q9HBH5; -.
DR jPOST; Q9HBH5; -.
DR MassIVE; Q9HBH5; -.
DR MaxQB; Q9HBH5; -.
DR PaxDb; Q9HBH5; -.
DR PeptideAtlas; Q9HBH5; -.
DR PRIDE; Q9HBH5; -.
DR ProteomicsDB; 81552; -.
DR Antibodypedia; 47311; 111 antibodies from 17 providers.
DR DNASU; 57665; -.
DR Ensembl; ENST00000381249.4; ENSP00000370648.3; ENSG00000240857.2.
DR GeneID; 57665; -.
DR KEGG; hsa:57665; -.
DR MANE-Select; ENST00000381249.4; ENSP00000370648.3; NM_020905.4; NP_065956.1.
DR UCSC; uc002rcx.5; human.
DR CTD; 57665; -.
DR DisGeNET; 57665; -.
DR GeneCards; RDH14; -.
DR HGNC; HGNC:19979; RDH14.
DR HPA; ENSG00000240857; Low tissue specificity.
DR neXtProt; NX_Q9HBH5; -.
DR OpenTargets; ENSG00000240857; -.
DR PharmGKB; PA134872714; -.
DR VEuPathDB; HostDB:ENSG00000240857; -.
DR eggNOG; KOG1208; Eukaryota.
DR GeneTree; ENSGT00940000160181; -.
DR HOGENOM; CLU_010194_44_5_1; -.
DR InParanoid; Q9HBH5; -.
DR OMA; GVQGKCF; -.
DR OrthoDB; 694318at2759; -.
DR PhylomeDB; Q9HBH5; -.
DR TreeFam; TF105429; -.
DR BRENDA; 1.1.1.300; 2681.
DR BRENDA; 1.1.1.71; 2681.
DR PathwayCommons; Q9HBH5; -.
DR Reactome; R-HSA-5365859; RA biosynthesis pathway.
DR SignaLink; Q9HBH5; -.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 57665; 5 hits in 1075 CRISPR screens.
DR GeneWiki; RDH14; -.
DR GenomeRNAi; 57665; -.
DR Pharos; Q9HBH5; Tdark.
DR PRO; PR:Q9HBH5; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HBH5; protein.
DR Bgee; ENSG00000240857; Expressed in heart left ventricle and 98 other tissues.
DR ExpressionAtlas; Q9HBH5; baseline and differential.
DR Genevisible; Q9HBH5; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0102354; F:11-cis-retinol dehydrogenase activity; IEA:RHEA.
DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; HDA: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 1: Evidence at protein level;
KW Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..336
FT /note="Retinol dehydrogenase 14"
FT /id="PRO_0000054770"
FT ACT_SITE 217
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT BINDING 50..56
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 5
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
SQ SEQUENCE 336 AA; 36865 MW; BCC17B3CD6B70DED CRC64;
MAVATAAAVL AALGGALWLA ARRFVGPRVQ RLRRGGDPGL MHGKTVLITG ANSGLGRATA
AELLRLGARV IMGCRDRARA EEAAGQLRRE LRQAAECGPE PGVSGVGELI VRELDLASLR
SVRAFCQEML QEEPRLDVLI NNAGIFQCPY MKTEDGFEMQ FGVNHLGHFL LTNLLLGLLK
SSAPSRIVVV SSKLYKYGDI NFDDLNSEQS YNKSFCYSRS KLANILFTRE LARRLEGTNV
TVNVLHPGIV RTNLGRHIHI PLLVKPLFNL VSWAFFKTPV EGAQTSIYLA SSPEVEGVSG
RYFGDCKEEE LLPKAMDESV ARKLWDISEV MVGLLK
