DHRS3_HUMAN
ID DHRS3_HUMAN Reviewed; 302 AA.
AC O75911; B2R7F3; Q5VUY3; Q6UY38; Q9BUC8;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Short-chain dehydrogenase/reductase 3;
DE EC=1.1.1.300 {ECO:0000269|PubMed:9705317};
DE AltName: Full=DD83.1;
DE AltName: Full=Retinal short-chain dehydrogenase/reductase 1;
DE Short=retSDR1;
DE AltName: Full=Retinol dehydrogenase 17;
DE AltName: Full=Short chain dehydrogenase/reductase family 16C member 1;
GN Name=DHRS3; Synonyms=RDH17, SDR16C1; ORFNames=UNQ2424/PRO4983;
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] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP VARIANT ALA-2, AND CATALYTIC ACTIVITY.
RC TISSUE=Retina;
RX PubMed=9705317; DOI=10.1074/jbc.273.34.21790;
RA Haeseleer F., Huang J., Lebioda L., Saari J.C., Palczewski K.;
RT "Molecular characterization of a novel short-chain dehydrogenase/reductase
RT that reduces all-trans-retinal.";
RL J. Biol. Chem. 273:21790-21799(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-2.
RC TISSUE=Retina;
RA Haeseleer F., Palczewski K.;
RT "Structure of retinal short-chain dehydrogenase/reductase retSDR1 gene.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-2.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon endothelium;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [9]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11861404;
RA Cerignoli F., Guo X., Cardinali B., Rinaldi C., Casaletto J., Frati L.,
RA Screpanti I., Gudas L.J., Gulino A., Thiele C.J., Giannini G.;
RT "retSDR1, a short-chain retinol dehydrogenase/reductase, is retinoic acid-
RT inducible and frequently deleted in human neuroblastoma cell lines.";
RL Cancer Res. 62:1196-1204(2002).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Catalyzes the reduction of all-trans-retinal to all-trans-
CC retinol in the presence of NADPH. {ECO:0000269|PubMed:9705317}.
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:9705317};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75911-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75911-2; Sequence=VSP_013256, VSP_013257;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels found in
CC heart, placenta, lung, liver, kidney, pancreas, thyroid, testis,
CC stomach, trachea and spinal cord. Lower levels found in skeletal
CC muscle, intestine and lymph node. No expression detected in brain. In
CC the retina, expressed in cone but not rod outer segments.
CC {ECO:0000269|PubMed:11861404, ECO:0000269|PubMed:9705317}.
CC -!- INDUCTION: By retinoic acid. {ECO:0000269|PubMed:11861404}.
CC -!- MISCELLANEOUS: Located in a region of chromosome 1 which is often
CC deleted in aggressive neuroblastoma tumors.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ88460.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF061741; AAC63263.1; -; mRNA.
DR EMBL; AF179237; AAD55402.1; -; Genomic_DNA.
DR EMBL; AF179234; AAD55402.1; JOINED; Genomic_DNA.
DR EMBL; AF179235; AAD55402.1; JOINED; Genomic_DNA.
DR EMBL; AF179236; AAD55402.1; JOINED; Genomic_DNA.
DR EMBL; AY358093; AAQ88460.1; ALT_FRAME; mRNA.
DR EMBL; AK312961; BAG35800.1; -; mRNA.
DR EMBL; BX648476; CAI46033.1; -; mRNA.
DR EMBL; AL513016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL645761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71743.1; -; Genomic_DNA.
DR EMBL; BC002730; AAH02730.1; -; mRNA.
DR CCDS; CCDS146.1; -. [O75911-1]
DR RefSeq; NP_004744.2; NM_004753.6. [O75911-1]
DR AlphaFoldDB; O75911; -.
DR SMR; O75911; -.
DR BioGRID; 114675; 48.
DR IntAct; O75911; 6.
DR STRING; 9606.ENSP00000480439; -.
DR DrugBank; DB00162; Vitamin A.
DR SwissLipids; SLP:000001868; -.
DR iPTMnet; O75911; -.
DR PhosphoSitePlus; O75911; -.
DR BioMuta; DHRS3; -.
DR EPD; O75911; -.
DR jPOST; O75911; -.
DR MassIVE; O75911; -.
DR MaxQB; O75911; -.
DR PaxDb; O75911; -.
DR PeptideAtlas; O75911; -.
DR PRIDE; O75911; -.
DR ProteomicsDB; 50263; -. [O75911-1]
DR ProteomicsDB; 50264; -. [O75911-2]
DR Antibodypedia; 2554; 203 antibodies from 26 providers.
DR DNASU; 9249; -.
DR Ensembl; ENST00000616661.5; ENSP00000480439.1; ENSG00000162496.9. [O75911-1]
DR GeneID; 9249; -.
DR KEGG; hsa:9249; -.
DR MANE-Select; ENST00000616661.5; ENSP00000480439.1; NM_004753.7; NP_004744.2.
DR UCSC; uc031tpa.2; human. [O75911-1]
DR CTD; 9249; -.
DR DisGeNET; 9249; -.
DR GeneCards; DHRS3; -.
DR HGNC; HGNC:17693; DHRS3.
DR HPA; ENSG00000162496; Tissue enhanced (liver).
DR MIM; 612830; gene.
DR neXtProt; NX_O75911; -.
DR OpenTargets; ENSG00000162496; -.
DR PharmGKB; PA134952810; -.
DR VEuPathDB; HostDB:ENSG00000162496; -.
DR eggNOG; KOG1201; Eukaryota.
DR GeneTree; ENSGT00940000158724; -.
DR HOGENOM; CLU_010194_2_5_1; -.
DR InParanoid; O75911; -.
DR OMA; LCLRAQV; -.
DR OrthoDB; 1373099at2759; -.
DR PhylomeDB; O75911; -.
DR TreeFam; TF312837; -.
DR BioCyc; MetaCyc:ENSG00000162496-MON; -.
DR BRENDA; 1.1.1.300; 2681.
DR PathwayCommons; O75911; -.
DR Reactome; R-HSA-2187335; The retinoid cycle in cones (daylight vision).
DR Reactome; R-HSA-5365859; RA biosynthesis pathway.
DR SignaLink; O75911; -.
DR BioGRID-ORCS; 9249; 15 hits in 1079 CRISPR screens.
DR ChiTaRS; DHRS3; human.
DR GeneWiki; DHRS3; -.
DR GenomeRNAi; 9249; -.
DR Pharos; O75911; Tbio.
DR PRO; PR:O75911; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75911; protein.
DR Bgee; ENSG00000162496; Expressed in olfactory bulb and 200 other tissues.
DR ExpressionAtlas; O75911; baseline and differential.
DR Genevisible; O75911; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; IBA:GO_Central.
DR GO; GO:0042622; C:photoreceptor outer segment membrane; TAS:Reactome.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; TAS:Reactome.
DR GO; GO:0000166; F:nucleotide binding; TAS:ProtInc.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0060349; P:bone morphogenesis; IEA:Ensembl.
DR GO; GO:0060411; P:cardiac septum morphogenesis; IEA:Ensembl.
DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0003151; P:outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0048385; P:regulation of retinoic acid receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0001523; P:retinoid metabolic process; IBA:GO_Central.
DR GO; GO:0042572; P:retinol metabolic process; TAS:UniProtKB.
DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR InterPro; IPR032969; DHRS3.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR24322:SF483; PTHR24322:SF483; 1.
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 Alternative splicing; Lipid metabolism; Membrane; NADP; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..302
FT /note="Short-chain dehydrogenase/reductase 3"
FT /id="PRO_0000054644"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 188
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 115..167
FT /note="GDITILVNNAAVVHGKSLMDSDDDALLKSQHINTLGQFWTTKAFLPRMLELQ
FT N -> CSLGGSIPSTADHRLIPGKENILMWPGRELCLWQNGFARGTFGDSPMKLAPVT
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_013256"
FT VAR_SEQ 168..302
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_013257"
FT VARIANT 2
FT /note="V -> A (in dbSNP:rs1128251)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:9705317, ECO:0000269|Ref.2"
FT /id="VAR_067443"
SQ SEQUENCE 302 AA; 33548 MW; 8FB4A735278E242E CRC64;
MVWKRLGALV MFPLQMIYLV VKAAVGLVLP AKLRDLSREN VLITGGGRGI GRQLAREFAE
RGARKIVLWG RTEKCLKETT EEIRQMGTEC HYFICDVGNR EEVYQTAKAV REKVGDITIL
VNNAAVVHGK SLMDSDDDAL LKSQHINTLG QFWTTKAFLP RMLELQNGHI VCLNSVLALS
AIPGAIDYCT SKASAFAFME SLTLGLLDCP GVSATTVLPF HTSTEMFQGM RVRFPNLFPP
LKPETVARRT VEAVQLNQAL LLLPWTMHAL VILKSILPQA ALEEIHKFSG TYTCMNTFKG
RT
