DHRS4_HUMAN
ID DHRS4_HUMAN Reviewed; 278 AA.
AC Q9BTZ2; B2RB10; B7WNS9; D3YTB8; E2QRL8; O95162; Q20CR0; Q2LC19; Q2LE81;
AC Q58IU4; Q6E0Y1; Q6UWU3; Q71UQ6; Q8TD03; Q9H3N5; Q9NV08;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Dehydrogenase/reductase SDR family member 4 {ECO:0000303|PubMed:19027726};
DE EC=1.1.1.184 {ECO:0000269|PubMed:18571493, ECO:0000269|PubMed:19056333, ECO:0000269|PubMed:23128527};
DE AltName: Full=NADPH-dependent carbonyl reductase {ECO:0000250|UniProtKB:Q8WNV7};
DE Short=CR {ECO:0000250|UniProtKB:Q8WNV7};
DE AltName: Full=NADPH-dependent retinol dehydrogenase/reductase {ECO:0000303|PubMed:23128527};
DE Short=NRDR {ECO:0000303|PubMed:23128527};
DE Short=humNRDR;
DE AltName: Full=Peroxisomal short-chain alcohol dehydrogenase;
DE Short=PSCD;
DE AltName: Full=SCAD-SRL;
DE AltName: Full=Short chain dehydrogenase/reductase family 25C member 2 {ECO:0000303|PubMed:19027726};
DE Short=Protein SDR25C2 {ECO:0000303|PubMed:19027726};
DE AltName: Full=Short-chain dehydrogenase/reductase family member 4;
GN Name=DHRS4 {ECO:0000312|HGNC:HGNC:16985};
GN Synonyms=SDR25C2 {ECO:0000303|PubMed:19027726}; ORFNames=UNQ851/PRO1800;
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] (ISOFORMS 1; 2 AND 3), AND SUBCELLULAR LOCATION.
RX PubMed=10333503; DOI=10.1042/bj3400561;
RA Fransen M., Van Veldhoven P.P., Subramani S.;
RT "Identification of peroxisomal proteins by using M13 phage protein VI phage
RT display: molecular evidence that mammalian peroxisomes contain a 2,4-
RT dienoyl-CoA reductase.";
RL Biochem. J. 340:561-568(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Furukawa A., Ohnishi T., Huang D., Araki N., Ichikawa Y.;
RT "cDNA cloning and characterization of peroxisomal short-chain dehydrogenase
RT / reductase that reduces all-trans retinal to retinol.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RX PubMed=15473316;
RA Du J., Huang D.-Y., Liu G.-F., Wang G.-L., Xu X.-L., Wang B., Zhu L.;
RT "cDNA cloning of a short isoform of human liver NADP (H) -dependent retinol
RT dehydrogenase/reductase and analysis of its characteristics.";
RL Yi Chuan Xue Bao 31:661-667(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Tu Q., Yu L., Bi A., Li N., He W., Zhao S.;
RT "Molecular cloning and expression analysis of a novel human cDNA encoding a
RT protein homologous to human Hep27 protein.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7).
RA Li Y.F., Liu G.-F., Song X.-H., Yang Y.M., Zhong J.C., Du K., Zhu W.,
RA Huang D.-Y.;
RT "A minor misassignment error inside segmental duplication (MMEISD) of DHRS4
RT gene in human genome sequence.";
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Li Y.F., Liu G.-F., Song X.-H., Du K., Huang D.-Y.;
RT "cDNA cloning of a short isoform of human neuroblastoma NADP(H)-dependent
RT retinol dehydrogenase/reductase and analysis of its characteristics.";
RL Ai Bian Ji Bian Tu Bian 17:321-326(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM
RP 6), NUCLEOTIDE SEQUENCE [MRNA] OF 40-278 (ISOFORM 5), SUBCELLULAR LOCATION
RP (ISOFORM 4), AND TISSUE SPECIFICITY (ISOFORM 4).
RC TISSUE=Cervix carcinoma, and Neuroblastoma;
RX PubMed=17230527; DOI=10.1002/ijc.22306;
RA Song X.-H., Liang B., Liu G.-F., Li R., Xie J.-P., Du K., Huang D.-Y.;
RT "Expression of a novel alternatively spliced variant of NADP(H)-dependent
RT retinol dehydrogenase/reductase with deletion of exon 3 in cervical
RT squamous carcinoma.";
RL Int. J. Cancer 120:1618-1626(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, and Skeletal muscle;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140 (ISOFORM 5), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, INDUCTION BY PPAR-ALPHA LIGANDS, DOMAIN, AND
RP MUTAGENESIS OF THR-195.
RX PubMed=18571493; DOI=10.1016/j.abb.2008.06.002;
RA Matsunaga T., Endo S., Maeda S., Ishikura S., Tajima K., Tanaka N.,
RA Nakamura K.T., Imamura Y., Hara A.;
RT "Characterization of human DHRS4: an inducible short-chain
RT dehydrogenase/reductase enzyme with 3beta-hydroxysteroid dehydrogenase
RT activity.";
RL Arch. Biochem. Biophys. 477:339-347(2008).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DOMAIN, AND
RP MUTAGENESIS OF SER-176; PHE-179 AND THR-195.
RX PubMed=19056333; DOI=10.1016/j.abb.2008.11.014;
RA Endo S., Maeda S., Matsunaga T., Dhagat U., El-Kabbani O., Tanaka N.,
RA Nakamura K.T., Tajima K., Hara A.;
RT "Molecular determinants for the stereospecific reduction of 3-ketosteroids
RT and reactivity towards all-trans-retinal of a short-chain
RT dehydrogenase/reductase (DHRS4).";
RL Arch. Biochem. Biophys. 481:183-190(2009).
RN [15]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=19027726; DOI=10.1016/j.cbi.2008.10.040;
RA Persson B., Kallberg Y., Bray J.E., Bruford E., Dellaporta S.L.,
RA Favia A.D., Duarte R.G., Joernvall H., Kavanagh K.L., Kedishvili N.,
RA Kisiela M., Maser E., Mindnich R., Orchard S., Penning T.M., Thornton J.M.,
RA Adamski J., Oppermann U.;
RT "The SDR (short-chain dehydrogenase/reductase and related enzymes)
RT nomenclature initiative.";
RL Chem. Biol. Interact. 178:94-98(2009).
RN [16]
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 [17]
RP ALTERNATIVE SPLICING (ISOFORM 8), CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23128527; DOI=10.1159/000343326;
RA Yan Y., Song X., Liu G., Su Z., Du Y., Sui X., Chang X., Huang D.;
RT "Human NRDRB1, an alternatively spliced isoform of NADP(H)-dependent
RT retinol dehydrogenase/reductase enhanced enzymatic activity of Benzil.";
RL Cell. Physiol. Biochem. 30:1371-1382(2012).
RN [18]
RP SUBCELLULAR LOCATION (ISOFORM 7), AND FUNCTION.
RX PubMed=22227495; DOI=10.1016/j.gene.2011.12.033;
RA Su Z., Li R., Song X., Liu G., Li Y., Chang X., Li C., Huang D.;
RT "Identification of a novel isoform of DHRS4 protein with a nuclear
RT localization signal.";
RL Gene 494:161-167(2012).
RN [19]
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).
RN [20]
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).
RN [21]
RP MISCELLANEOUS.
RX PubMed=27323117; DOI=10.4238/gmr.15027752;
RA Su Z., Liu G., Song X., Liang B., Chang X., Huang D.;
RT "CpG island evolution in the mammalian DHRS4 gene cluster and its role in
RT the regulation of gene transcription.";
RL Genet. Mol. Res. 15:0-0(2016).
CC -!- FUNCTION: NADPH-dependent oxidoreductase which catalyzes the reduction
CC of a variety of compounds bearing carbonyl groups including
CC ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones
CC and quinones (PubMed:18571493, PubMed:19056333). Reduces 3-ketosteroids
CC and benzil into 3beta-hydroxysteroids and R-benzoin, respectively, in
CC contrast to the stereoselectivity of non-primate DHRS4s which produce
CC 3alpha-hydroxysteroids and S-benzoin (PubMed:19056333). Diplays low
CC activity toward all-trans-retinal and no activity toward 9-cis-retinal
CC as compared to non-primate mammals (PubMed:18571493, PubMed:19056333).
CC In the reverse reaction, catalyze the NAD-dependent oxidation of 3beta-
CC hydroxysteroids and alcohol, but with much lower efficiency
CC (PubMed:18571493, PubMed:19056333). Involved in the metabolism of
CC 3beta-hydroxysteroids, isatin and xenobiotic carbonyl compounds
CC (PubMed:18571493, PubMed:19056333). {ECO:0000269|PubMed:18571493,
CC ECO:0000269|PubMed:19056333}.
CC -!- FUNCTION: [Isoform 7]: No detected catalytic activity in vitro,
CC possibly due to the lack of catalytic site.
CC {ECO:0000269|PubMed:22227495}.
CC -!- FUNCTION: [Isoform 8]: NADPH-dependent oxidoreductase which catalyzes
CC the reduction of a variety of compounds bearing carbonyl groups
CC including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic
CC ketones and quinones. Involved in the metabolism of 3beta-
CC hydroxysteroids, isatin and xenobiotic carbonyl compounds. Has a higher
CC catalytic activity for xenobiotic alpha-dicarbonyl compounds, sucha as
CC benzil, than isoform 1 and is involved in benzil detoxification.
CC {ECO:0000269|PubMed:23128527}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a secondary alcohol + NADP(+) = a ketone + H(+) + NADPH;
CC Xref=Rhea:RHEA:19257, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087,
CC ChEBI:CHEBI:35681, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.184; Evidence={ECO:0000269|PubMed:18571493,
CC ECO:0000269|PubMed:19056333, ECO:0000269|PubMed:23128527};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19259;
CC Evidence={ECO:0000305|PubMed:18571493, ECO:0000305|PubMed:19056333,
CC ECO:0000305|PubMed:23128527};
CC -!- CATALYTIC ACTIVITY: [Isoform 8]:
CC Reaction=a secondary alcohol + NADP(+) = a ketone + H(+) + NADPH;
CC Xref=Rhea:RHEA:19257, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087,
CC ChEBI:CHEBI:35681, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.184; Evidence={ECO:0000269|PubMed:23128527};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19259;
CC Evidence={ECO:0000305|PubMed:23128527};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5beta-pregnane-20-one + NADP(+) = 5beta-pregnan-
CC 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:22944, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16229, ChEBI:CHEBI:30154, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:18571493,
CC ECO:0000269|PubMed:19056333, ECO:0000269|PubMed:23128527};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22946;
CC Evidence={ECO:0000269|PubMed:18571493, ECO:0000305|PubMed:19056333};
CC -!- CATALYTIC ACTIVITY: [Isoform 8]:
CC Reaction=3beta-hydroxy-5beta-pregnane-20-one + NADP(+) = 5beta-pregnan-
CC 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:22944, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16229, ChEBI:CHEBI:30154, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:23128527};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22946;
CC Evidence={ECO:0000305|PubMed:23128527};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-dihydrotestosterone + H(+) + NADPH = 5beta-androstane-
CC 3beta,17beta-diol + NADP(+); Xref=Rhea:RHEA:69012, ChEBI:CHEBI:2150,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36715, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:18571493,
CC ECO:0000269|PubMed:19056333};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69013;
CC Evidence={ECO:0000269|PubMed:18571493, ECO:0000305|PubMed:19056333};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-androstane-3,17-dione + H(+) + NADPH = 3beta-hydroxy-
CC 5beta-androstane-17-one + NADP(+); Xref=Rhea:RHEA:69036,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16985, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:89524;
CC Evidence={ECO:0000269|PubMed:18571493};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69037;
CC Evidence={ECO:0000269|PubMed:18571493};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + isatin + NADPH = 3-hydroxyindolin-2-one + NADP(+);
CC Xref=Rhea:RHEA:68608, ChEBI:CHEBI:15378, ChEBI:CHEBI:27539,
CC ChEBI:CHEBI:28536, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:23128527, ECO:0000305|PubMed:19056333};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68609;
CC Evidence={ECO:0000305|PubMed:19056333, ECO:0000305|PubMed:23128527};
CC -!- CATALYTIC ACTIVITY: [Isoform 8]:
CC Reaction=H(+) + isatin + NADPH = 3-hydroxyindolin-2-one + NADP(+);
CC Xref=Rhea:RHEA:68608, ChEBI:CHEBI:15378, ChEBI:CHEBI:27539,
CC ChEBI:CHEBI:28536, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:23128527};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68609;
CC Evidence={ECO:0000305|PubMed:23128527};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lithocholate + NADP(+) = 3-oxo-5beta-cholan-24-oate + H(+) +
CC NADPH; Xref=Rhea:RHEA:47496, ChEBI:CHEBI:11867, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29744, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:18571493};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:47498;
CC Evidence={ECO:0000305|PubMed:18571493};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxo-5beta-cholan-24-oate + H(+) + NADPH = isolithocholate +
CC NADP(+); Xref=Rhea:RHEA:47520, ChEBI:CHEBI:11867, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:87728;
CC Evidence={ECO:0000269|PubMed:18571493};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47521;
CC Evidence={ECO:0000305|PubMed:18571493};
CC -!- ACTIVITY REGULATION: Inhibited by flavonoids (quercetin and genistein),
CC cetylpyridium chloride, phenylhexane and valproic acid. Low inhibition
CC is observed with fatty acids (myristic acid and lauric acid). No
CC significant inhibition is observed with barbital, dicumarol,
CC indomethacin, metyrapone, ethacrynic acid, disulfiram, hexestrol and
CC benzodiazepines (diazepam and nitrazepam).
CC {ECO:0000269|PubMed:18571493}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 8]:
CC Kinetic parameters:
CC KM=5.1 uM for 5beta-Pregnane-3,20-dione(at pH7.4)
CC {ECO:0000269|PubMed:23128527};
CC KM=127.8 uM for 5beta-Androstan-17b-ol-3-one (at pH7.4)
CC {ECO:0000269|PubMed:23128527};
CC KM=475 uM for Isatin (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=1.8 uM for Benzil (at pH6) {ECO:0000269|PubMed:23128527};
CC KM=18.8 uM for 1-Phenylisatin (at pH6) {ECO:0000269|PubMed:23128527};
CC KM=2.2 uM for 9,10-Phenanthrenequinone (at pH7.4)
CC {ECO:0000269|PubMed:23128527};
CC KM=7.5 uM for Menadione (at pH6) {ECO:0000269|PubMed:23128527};
CC Note=kcat is 3.4 min(-1) with 5beta-Pregnane-3,20-dione as substrate
CC (at pH7.4) (PubMed:23128527). kcat is 11.8 min(-1) with 5beta-
CC Androstan-17beta-ol-3-one as substrate (at pH7.4) (PubMed:23128527).
CC kcat is 475 min(-1) with Isatin as substrate (at pH6)
CC (PubMed:23128527). kcat is 3600 min(-1) with Benzil as substrate (at
CC pH6) (PubMed:23128527). kcat is 2570 min(-1) with 1-Phenylisatin as
CC substrate (at pH6) (PubMed:23128527). kcat is 737 min(-1) with 9,10-
CC Phenanthrenequinone as substrate (at pH7.4) (PubMed:23128527). kcat
CC is 27.1 min(-1) with Menadione as substrate (at pH6)
CC (PubMed:23128527). {ECO:0000269|PubMed:23128527};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.0029 mM for 5beta-Pregnane-3,20-dione(at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=4.6 uM for 5beta-Pregnane-3,20-dione(at pH7.4)
CC {ECO:0000269|PubMed:23128527};
CC KM=0.0049 mM for 5beta-Androstan-17b-ol-3-one (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=117 uM for 5beta-Androstan-17b-ol-3-one (at pH7.4)
CC {ECO:0000269|PubMed:23128527};
CC KM=0.01 mM for 5beta-Androstane-3,17-dione (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.0097 mM for 5beta-Pregnan-20alpha-ol-3-one (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.016 mM for 5alpha-Dihydrotestosterone (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.028 mM for 5alpha-Androstane-3,17-dione (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.035 mM for Dehydrolithocholic acid (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.024 mM for all-trans-Retinal (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.32 mM for Isatin (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=389 uM for Isatin (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=1.4 mM for Dimethyl-2-oxoglutarate (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.16 mM for 4-Hexanoylpyridine (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.036 mM for Hexanophenone (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=0.054 mM for Valerophenone (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=0.048 mM for n-Butyrophenone (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=1 mM for 4-Benzoylpyridine (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=0.55 mM for 3,4-hexanedione (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.2 mM for 2,3-heptanedione (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.005 mM for Benzil (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=7.1 uM for Benzil (at pH6) {ECO:0000269|PubMed:23128527};
CC KM=0.0015 mM for 4,4'-Dimethylbenzil (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=10 mM for 2,3-Pentanedione (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=54 mM for Diacetyl (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=13 mM for 4-Nitrobenzaldehyde (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=21 mM for Pyridine-4-aldehyde (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.0052 mM for 1-Phenylisatin (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=12.8 uM for 1-Phenylisatin (at pH6) {ECO:0000269|PubMed:23128527};
CC KM=0.0036 mM for 9,10-Phenanthrenequinone (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=3.4 uM for 9,10-Phenanthrenequinone (at pH7.4)
CC {ECO:0000269|PubMed:23128527};
CC KM=0.18 mM for Menadione (at pH6) {ECO:0000269|PubMed:18571493};
CC KM=29.7 uM for Menadione (at pH6) {ECO:0000269|PubMed:23128527};
CC KM=0.12 mM for 6-tert-butyl-2,3-epoxy-5-cyclohexene-1,4-dione (at
CC pH6) {ECO:0000269|PubMed:18571493};
CC KM=0.089 mM for 1,4-Naphthoquinone (at pH6)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.008 mM for 5b-Pregnan-3b-ol-20-one (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.0041 mM for 5b-Androstane-3b,17b-diol (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.0079 mM for 5b-Androstan-3b-ol-17-one (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.008 mM for 5b-Pregnane-3b,20a-diol (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.0084 mM for S-Phenyl-1-butanol (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.093 mM for S-1-Tetralol (at pH7.4)
CC {ECO:0000269|PubMed:18571493};
CC KM=0.24 mM for S-1-Indanol (at pH7.4) {ECO:0000269|PubMed:18571493};
CC Note=kcat is 3.8 min(-1) with 5beta-Pregnane-3,20-dione as substrate
CC (at pH7.4) (PubMed:18571493). kcat is 5 min(-1) with 5beta-Androstan-
CC 17beta-ol-3-one as substrate (at pH7.4) (PubMed:18571493). kcat is
CC 4.6 min(-1) with 5beta-Androstane-3,17-dione as substrate (at pH7.4)
CC (PubMed:18571493). kcat is 4.2 min(-1) with 5b-Pregnan-20alpha-ol-3-
CC one as substrate (at pH7.4) (PubMed:18571493). kcat is 5.7 min(-1)
CC with 5alpha-Dihydrotestosterone as substrate (at pH7.4)
CC (PubMed:18571493). kcat 5.8 is min(-1) with 5alpha-Androstane-3,17-
CC dione as substrate (at pH7.4) (PubMed:18571493). kcat is 0.41 min(-1)
CC with Testosterone as substrate (at pH7.4) (PubMed:18571493). kcat is
CC 0.02 min(-1) with 5alpha-Pregnane-3,20-dione as substrate (at pH7.4)
CC (PubMed:18571493). kcat is 2.6 min(-1) with Dehydrolithocholic acid
CC as substrate (at pH7.4) (PubMed:18571493). kcat is 3.2 min(-1) with
CC all-trans-Retinal as substrate (at pH7.4) (PubMed:18571493). kcat is
CC 1900 min(-1) with Isatin as substrate (at pH6) (PubMed:18571493).
CC kcat is 2000 min(-1) with Dimethyl-2-oxoglutarate as substrate (at
CC pH6) (PubMed:18571493). kcat is 2000 min(-1) with 4-Hexanoylpyridine
CC as substrate (at pH6) (PubMed:18571493). kcat is 160 min(-1) with
CC Hexanophenone as substrate (at pH6) (PubMed:18571493). kcat is 120
CC min(-1) with Valerophenone as substrate (at pH6) (PubMed:18571493).
CC kcat is 51 min(-1) with n-Butyrophenone as substrate (at pH6)
CC (PubMed:18571493). kcat is 120 min(-1) with 4-Benzoylpyridine as
CC substrate (at pH6) (PubMed:18571493). kcat is 980 min(-1) with 3,4-
CC Hexanedione as substrate (at pH6) (PubMed:18571493). kcat is 2410
CC min(-1) with 2,3-Heptanedione as substrate (at pH6)
CC (PubMed:18571493). kcat is 1900 min(-1) with Benzil as substrate (at
CC pH6) (PubMed:18571493). kcat is 220 min(-1) with 4,4'-Dimethylbenzil
CC as substrate (at pH6) (PubMed:18571493). kcat is 1600 min(-1) with
CC 2,3-Pentanedione as substrate (at pH6) (PubMed:18571493). kcat is
CC 1700 min(-1) with Diacetyl as substrate (at pH6) (PubMed:18571493).
CC kcat is 1000 min(-1) with 4-Nitrobenzaldehyde as substrate (at pH6)
CC (PubMed:18571493). kcat is 280 min(-1) with Pyridine-4-aldehyde as
CC substrate (at pH6) (PubMed:18571493). kcat is 2500 min(-1) with 1-
CC Phenylisatin as substrate (at pH6) (PubMed:18571493). kcat is 710
CC min(-1) with 9,10-Phenanthrenequinone as substrate (at pH6)
CC (PubMed:18571493). kcat is 39 min(-1) with Menadione as substrate (at
CC pH6) (PubMed:18571493). kcat is 120 min(-1) with 6-tert-butyl-2,3-
CC epoxy-5-cyclohexene-1,4-dione as substrate (at pH6)
CC (PubMed:18571493). kcat is 53 min(-1) with 1,4-Naphthoquinone as
CC substrate (at pH6) (PubMed:18571493). kcat is 2.5 min(-1) with 5beta-
CC Pregnan-3beta-ol-20-one as substrate (at pH6) (PubMed:18571493). kcat
CC is 0.42 min(-1) with 5beta-Pregnan-3beta-ol-20-one as substrate (at
CC pH6) (PubMed:19056333). kcat is 1 min(-1) with 5beta-Androstane-
CC 3beta,17beta-diol as substrate (at pH6) (PubMed:18571493). kcat is
CC 0.24 min(-1) with 5beta-Androstane-3beta,17beta-diol as substrate (at
CC pH6) (PubMed:19056333). kcat is 1 min(-1) with 5beta-Androstan-3beta-
CC ol-17-one as substrate (at pH7.4) (PubMed:18571493). kcat is 0.84
CC min(-1) with 5beta-Pregnane-3beta,20alpha-diol as substrate (at
CC pH7.4) (PubMed:18571493). kcat is 0.86 min(-1) with 5alpha-
CC Androstane-3beta,17beta-diol as substrate (at pH7.4)
CC (PubMed:18571493). kcat is 0.43 min(-1) with 5alpha-Pregnane-3beta-
CC ol-20-one as substrate (at pH7.4) (PubMed:18571493). kcat is 0.21
CC min(-1) with Isolithocholic acid as substrate (at pH7.4)
CC (PubMed:18571493). kcat is 0.21 min(-1) with Isolithocholic acid as
CC substrate (at pH7.4) (PubMed:19056333). kcat is 0.02 min(-1) with
CC 5alpha-Androstan-3beta-ol-17-one as substrate (at pH7.4)
CC (PubMed:18571493). kcat is 4.5 min(-1) with S-Phenyl-1-butanol as
CC substrate (at pH7.4) (PubMed:18571493). kcat is 15 min(-1) with S-1-
CC Tetralol as substrate (at pH7.4) (PubMed:18571493). kcat is 11 min(-
CC 1) with S-1-Indanol as substrate (at pH7.4) (PubMed:18571493). kcat
CC is 0.2 min(-1) with all-trans-Retinol as substrate (at pH7.4)
CC (PubMed:18571493). {ECO:0000269|PubMed:18571493,
CC ECO:0000269|PubMed:19056333};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:18571493}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Peroxisome
CC {ECO:0000269|PubMed:10333503, ECO:0000269|PubMed:17230527}.
CC Note=Isoform 4 is not peroxisomal. {ECO:0000269|PubMed:17230527}.
CC -!- SUBCELLULAR LOCATION: [Isoform 7]: Nucleus
CC {ECO:0000269|PubMed:22227495}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1; Synonyms=SDR-SRL3;
CC IsoId=Q9BTZ2-1; Sequence=Displayed;
CC Name=2; Synonyms=SDR-SRL1;
CC IsoId=Q9BTZ2-2; Sequence=VSP_008586;
CC Name=3; Synonyms=SDR-SRL2;
CC IsoId=Q9BTZ2-3; Sequence=VSP_008585;
CC Name=4; Synonyms=NRDRB1;
CC IsoId=Q9BTZ2-4; Sequence=VSP_031436;
CC Name=5; Synonyms=NRDRB2;
CC IsoId=Q9BTZ2-5; Sequence=VSP_031436, VSP_031438;
CC Name=6; Synonyms=NRDRA1;
CC IsoId=Q9BTZ2-6; Sequence=VSP_031435;
CC Name=7; Synonyms=NRDRA2;
CC IsoId=Q9BTZ2-7; Sequence=VSP_031437, VSP_031439;
CC Name=8; Synonyms=NRDRB1 {ECO:0000303|PubMed:23128527};
CC IsoId=Q9BTZ2-8; Sequence=VSP_044947, VSP_031436;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Predominantly expressed in normal
CC cervix (at protein level). {ECO:0000269|PubMed:17230527}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Expressed in some neoplastic cervical
CC tissues, but not in normal cervix (at protein level).
CC {ECO:0000269|PubMed:17230527}.
CC -!- TISSUE SPECIFICITY: [Isoform 5]: Expressed in a few neoplastic cervical
CC tissues. {ECO:0000269|PubMed:17230527}.
CC -!- TISSUE SPECIFICITY: [Isoform 6]: Expressed in a few neoplastic cervical
CC tissues. {ECO:0000269|PubMed:17230527}.
CC -!- TISSUE SPECIFICITY: [Isoform 8]: High expression in liver.
CC {ECO:0000269|PubMed:23128527}.
CC -!- INDUCTION: Induced by PPARA ligands clofibrate and Wy14,643.
CC {ECO:0000269|PubMed:18571493}.
CC -!- DOMAIN: The C-terminus peroxisomal targeting signal tripeptide is
CC important for peroxisomal import. Once in the peroxisome, it is
CC involved in intersubunit interactions. {ECO:0000250|UniProtKB:Q8WNV7}.
CC -!- DOMAIN: Three specific residues, Ser-176, Phe-179 and Thr-195 are
CC conserved between primates whereas the respective residues are
CC phenylalanine, leucine, and asparagine in the other mammal enzymes
CC (PubMed:18571493, PubMed:19056333). The two residues at positions 176
CC and 179 are molecular determinants responsible for the stereoselective
CC reduction of 3-ketosteroids and benzil (PubMed:19056333). The presence
CC of an asparagine at position 195 is important for the maintenance of
CC the quaternary structure and stability at cold temperature
CC (PubMed:18571493, PubMed:19056333). The absence of an asparagine at
CC position 195 destabilizes the quaternary structure, thereby affecting
CC catalytic efficiency toward some substrates and decreasing stability at
CC cold temperature (PubMed:18571493, PubMed:19056333).
CC {ECO:0000269|PubMed:18571493, ECO:0000269|PubMed:19056333}.
CC -!- MISCELLANEOUS: Primate DHRS4s display different stereoselectivity and
CC catalytic efficiency in the oxidoreduction of some substrates as
CC compared to other mammal DHRS4s due to a difference in conserved amino
CC acid residues (PubMed:18571493, PubMed:19056333). Three homologous
CC proteins DHRS4, DHRS4L1, and DHRS4L2 are derived from gene duplication
CC of DHRS4, and the gene cluster is arranged in tandem in chromosome 14
CC (PubMed:27323117). {ECO:0000269|PubMed:18571493,
CC ECO:0000269|PubMed:19056333, ECO:0000269|PubMed:27323117}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD02292.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAL61824.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB18775.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG37057.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF044127; AAD02292.1; ALT_INIT; mRNA.
DR EMBL; AB045131; BAB18775.1; ALT_INIT; mRNA.
DR EMBL; AY071856; AAL61824.2; ALT_INIT; mRNA.
DR EMBL; AF064256; AAQ13444.1; -; mRNA.
DR EMBL; AY616182; AAT70757.1; -; mRNA.
DR EMBL; DQ344810; ABD75823.1; -; mRNA.
DR EMBL; AY943857; AAX49568.1; -; mRNA.
DR EMBL; DQ325464; ABC61320.1; -; mRNA.
DR EMBL; DQ338571; ABC61321.1; -; mRNA.
DR EMBL; AK001870; BAA91953.1; -; mRNA.
DR EMBL; AK314448; BAG37057.1; ALT_INIT; mRNA.
DR EMBL; AY358638; AAQ89001.1; -; mRNA.
DR EMBL; AL136419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003019; AAH03019.1; -; mRNA.
DR CCDS; CCDS61408.1; -. [Q9BTZ2-7]
DR CCDS; CCDS61409.1; -. [Q9BTZ2-2]
DR CCDS; CCDS61410.1; -. [Q9BTZ2-4]
DR CCDS; CCDS61411.1; -. [Q9BTZ2-5]
DR CCDS; CCDS61412.1; -. [Q9BTZ2-3]
DR CCDS; CCDS9605.1; -. [Q9BTZ2-1]
DR RefSeq; NP_001269916.1; NM_001282987.1. [Q9BTZ2-7]
DR RefSeq; NP_001269917.1; NM_001282988.1. [Q9BTZ2-4]
DR RefSeq; NP_001269918.1; NM_001282989.1. [Q9BTZ2-2]
DR RefSeq; NP_001269919.1; NM_001282990.1. [Q9BTZ2-5]
DR RefSeq; NP_001269920.1; NM_001282991.1. [Q9BTZ2-3]
DR RefSeq; NP_066284.2; NM_021004.3. [Q9BTZ2-1]
DR PDB; 3O4R; X-ray; 1.70 A; A/B/C/D=19-278.
DR PDBsum; 3O4R; -.
DR AlphaFoldDB; Q9BTZ2; -.
DR SMR; Q9BTZ2; -.
DR BioGRID; 116107; 84.
DR IntAct; Q9BTZ2; 42.
DR STRING; 9606.ENSP00000326219; -.
DR DrugBank; DB00162; Vitamin A.
DR iPTMnet; Q9BTZ2; -.
DR PhosphoSitePlus; Q9BTZ2; -.
DR BioMuta; DHRS4; -.
DR DMDM; 308153604; -.
DR EPD; Q9BTZ2; -.
DR jPOST; Q9BTZ2; -.
DR MassIVE; Q9BTZ2; -.
DR MaxQB; Q9BTZ2; -.
DR PaxDb; Q9BTZ2; -.
DR PeptideAtlas; Q9BTZ2; -.
DR PRIDE; Q9BTZ2; -.
DR ProteomicsDB; 15267; -.
DR ProteomicsDB; 79032; -. [Q9BTZ2-1]
DR ProteomicsDB; 79033; -. [Q9BTZ2-2]
DR ProteomicsDB; 79034; -. [Q9BTZ2-3]
DR ProteomicsDB; 79035; -. [Q9BTZ2-4]
DR ProteomicsDB; 79036; -. [Q9BTZ2-5]
DR ProteomicsDB; 79037; -. [Q9BTZ2-6]
DR ProteomicsDB; 79038; -. [Q9BTZ2-7]
DR Antibodypedia; 8732; 188 antibodies from 25 providers.
DR DNASU; 10901; -.
DR Ensembl; ENST00000313250.10; ENSP00000326219.5; ENSG00000157326.19. [Q9BTZ2-1]
DR Ensembl; ENST00000397074.7; ENSP00000380264.3; ENSG00000157326.19. [Q9BTZ2-3]
DR Ensembl; ENST00000397075.7; ENSP00000380265.3; ENSG00000157326.19. [Q9BTZ2-2]
DR Ensembl; ENST00000558263.5; ENSP00000453367.1; ENSG00000157326.19. [Q9BTZ2-7]
DR Ensembl; ENST00000558581.5; ENSP00000452645.1; ENSG00000157326.19. [Q9BTZ2-4]
DR Ensembl; ENST00000559632.5; ENSP00000453983.1; ENSG00000157326.19. [Q9BTZ2-5]
DR Ensembl; ENST00000643978.1; ENSP00000493736.1; ENSG00000284807.2. [Q9BTZ2-7]
DR Ensembl; ENST00000645602.1; ENSP00000496349.1; ENSG00000284807.2. [Q9BTZ2-2]
DR Ensembl; ENST00000645612.2; ENSP00000494364.1; ENSG00000284807.2. [Q9BTZ2-1]
DR Ensembl; ENST00000646997.1; ENSP00000495877.1; ENSG00000284807.2. [Q9BTZ2-5]
DR Ensembl; ENST00000647030.1; ENSP00000496426.1; ENSG00000284807.2. [Q9BTZ2-4]
DR Ensembl; ENST00000647154.1; ENSP00000495868.1; ENSG00000284807.2. [Q9BTZ2-3]
DR GeneID; 10901; -.
DR KEGG; hsa:10901; -.
DR MANE-Select; ENST00000313250.10; ENSP00000326219.5; NM_021004.4; NP_066284.2.
DR UCSC; uc001wla.5; human. [Q9BTZ2-1]
DR CTD; 10901; -.
DR DisGeNET; 10901; -.
DR GeneCards; DHRS4; -.
DR HGNC; HGNC:16985; DHRS4.
DR HPA; ENSG00000157326; Low tissue specificity.
DR MIM; 611596; gene.
DR neXtProt; NX_Q9BTZ2; -.
DR OpenTargets; ENSG00000157326; -.
DR PharmGKB; PA128395792; -.
DR VEuPathDB; HostDB:ENSG00000157326; -.
DR eggNOG; KOG0725; Eukaryota.
DR GeneTree; ENSGT00940000158919; -.
DR HOGENOM; CLU_010194_1_1_1; -.
DR InParanoid; Q9BTZ2; -.
DR OMA; WEVANVI; -.
DR OrthoDB; 1194344at2759; -.
DR PhylomeDB; Q9BTZ2; -.
DR TreeFam; TF315405; -.
DR BRENDA; 1.1.1.300; 2681.
DR PathwayCommons; Q9BTZ2; -.
DR Reactome; R-HSA-5365859; RA biosynthesis pathway.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR SignaLink; Q9BTZ2; -.
DR BioGRID-ORCS; 10901; 13 hits in 1072 CRISPR screens.
DR ChiTaRS; DHRS4; human.
DR EvolutionaryTrace; Q9BTZ2; -.
DR GeneWiki; DHRS4; -.
DR GenomeRNAi; 10901; -.
DR Pharos; Q9BTZ2; Tbio.
DR PRO; PR:Q9BTZ2; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9BTZ2; protein.
DR Bgee; ENSG00000157326; Expressed in right lobe of liver and 96 other tissues.
DR ExpressionAtlas; Q9BTZ2; baseline and differential.
DR Genevisible; Q9BTZ2; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005778; C:peroxisomal membrane; HDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0000253; F:3-keto sterol reductase activity; IDA:UniProtKB.
DR GO; GO:0033703; F:3beta-hydroxy-5beta-steroid dehydrogenase activity; IEA:RHEA.
DR GO; GO:0018455; F:alcohol dehydrogenase [NAD(P)+] activity; IDA:UniProtKB.
DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; TAS:Reactome.
DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IDA:UniProtKB.
DR GO; GO:0006066; P:alcohol metabolic process; IDA:UniProtKB.
DR GO; GO:0042180; P:cellular ketone metabolic process; IDA:UniProtKB.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:UniProtKB.
DR GO; GO:0042574; P:retinal metabolic process; IBA:GO_Central.
DR GO; GO:0008202; P:steroid metabolic process; IDA:UniProtKB.
DR InterPro; IPR029511; DHRS4-like.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR43943:SF8; PTHR43943:SF8; 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 3D-structure; Acetylation; Alternative splicing; NADP; Nucleus;
KW Oxidoreductase; Peroxisome; Phosphoprotein; Reference proteome.
FT CHAIN 1..278
FT /note="Dehydrogenase/reductase SDR family member 4"
FT /id="PRO_0000054647"
FT MOTIF 276..278
FT /note="Peroxisomal targeting signal"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT ACT_SITE 182
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 36..60
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT BINDING 169
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q99714"
FT BINDING 186
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT SITE 176
FT /note="Responsible for the stereoselective reduction of 3-
FT ketosteroids into 3beta-hydroxysteroids and benzil into R-
FT benzoin"
FT /evidence="ECO:0000269|PubMed:19056333"
FT SITE 179
FT /note="Responsible for the stereoselective reduction of 3-
FT ketosteroids into 3beta-hydroxysteroids and benzil into R-
FT benzoin"
FT /evidence="ECO:0000269|PubMed:19056333"
FT MOD_RES 92
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 92
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 105
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 216
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 216
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 227
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 234
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT VAR_SEQ 1..18
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_044947"
FT VAR_SEQ 19..221
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:17230527"
FT /id="VSP_031435"
FT VAR_SEQ 103..222
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10333503"
FT /id="VSP_008585"
FT VAR_SEQ 103..136
FT /note="Missing (in isoform 4, isoform 5 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:17230527"
FT /id="VSP_031436"
FT VAR_SEQ 137..222
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10333503,
FT ECO:0000303|PubMed:15473316"
FT /id="VSP_008586"
FT VAR_SEQ 137..188
FT /note="TLDINVKAPALMTKAVVPEMEKRGGGSVVIVSSIAAFSPSPGFSPYNVSKTA
FT -> RRLSGDRVFHSSLQSISSLDGQGKRGKHERNPADKKVRRARGLCWHRVFPVL (in
FT isoform 7)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_031437"
FT VAR_SEQ 178..222
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:17230527"
FT /id="VSP_031438"
FT VAR_SEQ 189..278
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_031439"
FT VARIANT 31
FT /note="A -> T (in dbSNP:rs1043442)"
FT /id="VAR_057272"
FT VARIANT 202
FT /note="P -> S (in dbSNP:rs1043650)"
FT /id="VAR_061846"
FT MUTAGEN 176
FT /note="S->F: Decreased reduction activity for benzil,
FT isatin and retinal and increased activity for 5beta-
FT Pregnane-3,20-dione and 5beta-Dihydrotestosterone. No
FT change of stereoselectivity in 3-ketosteroids reduction and
FT no change in 3beta-hydroxysteroid oxidation. Decreased
FT reduction activity for isatin and increased activity for
FT 5beta-Pregnane-3,20-dione, 5beta-Dihydrotestosterone,
FT benzil and retinal; when associated with L-179. Change in
FT stereoselective activity by the reduction of 5beta-
FT Pregnane-3,20-dione predominantly to the 3alpha-
FT hydroxysteroid; when associated with L-179. Switch from
FT 3beta-hydroxysteroid to 3alpha-hydroxysteroid oxidation;
FT when associated with L-179. Loss of cold catalytic
FT inactivation; when associated with L-179 and N-195.
FT Increased reduction activity for renital and oxidation
FT activity for retinol; when associated with L-179 and N-
FT 195."
FT /evidence="ECO:0000269|PubMed:19056333"
FT MUTAGEN 179
FT /note="F->L: Decreased reduction activity for isatin and
FT increased activity for 5beta-Pregnane-3,20-dione, 5beta-
FT Dihydrotestosterone, benzil and retinal; when associated
FT with F-176. Change in stereoselective activity by the
FT reduction of 5beta-Pregnane-3,20-dione predominantly to the
FT 3alpha-hydroxysteroid; when associated with F-176. Switch
FT from 3beta-hydroxysteroid to 3alpha-hydroxysteroid
FT oxidation; when associated with F-176. Loss of cold
FT catalytic inactivation; when associated with F-176 and N-
FT 195. Increased reduction activity for renital and oxidation
FT activity for retinol; when associated with F-176 and N-
FT 195."
FT /evidence="ECO:0000269|PubMed:19056333"
FT MUTAGEN 195
FT /note="T->N: Loss of cold catalytic inactivation. Loss of
FT cold catalytic inactivation; when associated with F-176 and
FT L-179. Switch in stereoselective activity from 3beta-
FT hydroxysteroid to 3alpha-hydroxysteroid oxidation; when
FT associated with F-176 and L-179. Increased reduction
FT activity for renital and oxidation activity for retinol;
FT when associated with F-176 and L-179."
FT /evidence="ECO:0000269|PubMed:18571493,
FT ECO:0000269|PubMed:19056333"
FT CONFLICT 37
FT /note="V -> A (in Ref. 8; BAA91953)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="R -> W (in Ref. 7; ABC61321)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="H -> M (in Ref. 4; AAQ13444)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="T -> M (in Ref. 1; AAD02292)"
FT /evidence="ECO:0000305"
FT CONFLICT 126
FT /note="I -> L (in Ref. 1; AAD02292)"
FT /evidence="ECO:0000305"
FT TURN 29..32
FT /evidence="ECO:0007829|PDB:3O4R"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 43..54
FT /evidence="ECO:0007829|PDB:3O4R"
FT STRAND 58..64
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 66..78
FT /evidence="ECO:0007829|PDB:3O4R"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 93..107
FT /evidence="ECO:0007829|PDB:3O4R"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:3O4R"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 131..141
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 143..158
FT /evidence="ECO:0007829|PDB:3O4R"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 180..200
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:3O4R"
FT STRAND 205..212
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 227..237
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 245..248
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 249..255
FT /evidence="ECO:0007829|PDB:3O4R"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:3O4R"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:3O4R"
FT MOD_RES Q9BTZ2-5:140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
SQ SEQUENCE 278 AA; 29537 MW; 3B06A229E1BBE47B CRC64;
MHKAGLLGLC ARAWNSVRMA SSGMTRRDPL ANKVALVTAS TDGIGFAIAR RLAQDGAHVV
VSSRKQQNVD QAVATLQGEG LSVTGTVCHV GKAEDRERLV ATAVKLHGGI DILVSNAAVN
PFFGSIMDVT EEVWDKTLDI NVKAPALMTK AVVPEMEKRG GGSVVIVSSI AAFSPSPGFS
PYNVSKTALL GLTKTLAIEL APRNIRVNCL APGLIKTSFS RMLWMDKEKE ESMKETLRIR
RLGEPEDCAG IVSFLCSEDA SYITGETVVV GGGTPSRL
