ID AK1BA_HUMAN Reviewed; 316 AA. AC O60218; A4D1P1; O75890; Q6FHF3; Q8IWZ1; DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 08-FEB-2011, sequence version 2. DT 27-MAR-2024, entry version 200. DE RecName: Full=Aldo-keto reductase family 1 member B10; DE EC=1.1.1.300 {ECO:0000269|PubMed:12732097}; DE EC=1.1.1.54 {ECO:0000269|PubMed:19563777}; DE AltName: Full=ARL-1 {ECO:0000303|PubMed:9565553}; DE AltName: Full=Aldose reductase-like; DE AltName: Full=Aldose reductase-related protein; DE Short=ARP; DE Short=hARP; DE AltName: Full=Small intestine reductase; DE Short=SI reductase; GN Name=AKR1B10; Synonyms=AKR1B11; 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], VARIANT ASP-313, FUNCTION, TISSUE SPECIFICITY, RP AND INDUCTION. RC TISSUE=Liver tumor; RX PubMed=9565553; DOI=10.1074/jbc.273.19.11429; RA Cao D., Fan S.T., Chung S.S.M.; RT "Identification and characterization of a novel human aldose reductase-like RT gene."; RL J. Biol. Chem. 273:11429-11435(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Small intestine; RX PubMed=9765596; DOI=10.1016/s0167-4781(98)00109-2; RA Hyndman D.J., Flynn T.G.; RT "Sequence and expression levels in human tissues of a new member of the RT aldo-keto reductase family."; RL Biochim. Biophys. Acta 1399:198-202(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ASP-313. RA Heringlake S.; RT "Representational difference analysis based identification and full-length RT sequencing of a gene of the aldo-ketoreductase family strongly RT overexpressed in hepatocellular carcinoma."; RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-313. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-313. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [8] 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-313. RC TISSUE=Pancreas; 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 [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 232-316, AND VARIANT ASP-313. RX PubMed=9537432; DOI=10.1002/hep.510270408; RA Scuric Z., Stain S.C., Anderson W.F., Hwang J.-J.; RT "New member of aldose reductase family proteins overexpressed in human RT hepatocellular carcinoma."; RL Hepatology 27:943-950(1998). RN [11] RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, RP FUNCTION, AND SUBSTRATE SPECIFICITY. RX PubMed=12732097; DOI=10.1042/bj20021818; RA Crosas B., Hyndman D.J., Gallego O., Martras S., Pares X., Flynn T.G., RA Farres J.; RT "Human aldose reductase and human small intestine aldose reductase are RT efficient retinal reductases: consequences for retinoid metabolism."; RL Biochem. J. 373:973-979(2003). RN [12] RP INDUCTION. RX PubMed=15755999; DOI=10.1158/1078-0432.ccr-04-1238; RA Fukumoto S., Yamauchi N., Moriguchi H., Hippo Y., Watanabe A., RA Shibahara J., Taniguchi H., Ishikawa S., Ito H., Yamamoto S., Iwanari H., RA Hironaka M., Ishikawa Y., Niki T., Sohara Y., Kodama T., Nishimura M., RA Fukayama M., Dosaka-Akita H., Aburatani H.; RT "Overexpression of the aldo-keto reductase family protein AKR1B10 is highly RT correlated with smokers' non-small cell lung carcinomas."; RL Clin. Cancer Res. 11:1776-1785(2005). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-125 AND LYS-263, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=21585341; DOI=10.1042/bj20110111; RA Luo D.X., Huang M.C., Ma J., Gao Z., Liao D.F., Cao D.; RT "Aldo-keto reductase family 1, member B10 is secreted through a lysosome- RT mediated non-classical pathway."; RL Biochem. J. 438:71-80(2011). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=19563777; DOI=10.1016/j.bbrc.2009.06.123; RA Zhong L., Liu Z., Yan R., Johnson S., Zhao Y., Fang X., Cao D.; RT "Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid- RT derived alpha, beta-unsaturated carbonyls at physiological levels."; RL Biochem. Biophys. Res. Commun. 387:245-250(2009). RN [16] RP FUNCTION, MUTAGENESIS OF CYS-299, CATALYTIC ACTIVITY, SUBSTRATE RP SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=19013440; DOI=10.1016/j.cbi.2008.10.021; RA Martin H.J., Maser E.; RT "Role of human aldo-keto-reductase AKR1B10 in the protection against toxic RT aldehydes."; RL Chem. Biol. Interact. 178:145-150(2009). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH TOLRESTAT AND NADP, RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, CATALYTIC RP ACTIVITY, AND MUTAGENESIS OF LYS-125 AND VAL-301. RX PubMed=18087047; DOI=10.1073/pnas.0705659105; RA Gallego O., Ruiz F.X., Ardevol A., Dominguez M., Alvarez R., de Lera A.R., RA Rovira C., Farres J., Fita I., Pares X.; RT "Structural basis for the high all-trans-retinaldehyde reductase activity RT of the tumor marker AKR1B10."; RL Proc. Natl. Acad. Sci. U.S.A. 104:20764-20769(2007). RN [18] RP VARIANT [LARGE SCALE ANALYSIS] ASP-313, AND IDENTIFICATION BY MASS RP 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). CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of a wide variety of CC carbonyl-containing compounds to their corresponding alcohols CC (PubMed:9565553, PubMed:18087047, PubMed:12732097, PubMed:19013440, CC PubMed:19563777). Displays strong enzymatic activity toward all-trans- CC retinal, 9-cis-retinal, and 13-cis-retinal (PubMed:12732097, CC PubMed:18087047). Plays a critical role in detoxifying dietary and CC lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4- CC hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their CC glutathione-conjugates carbonyls (GS-carbonyls) (PubMed:19013440, CC PubMed:19563777). Displays no reductase activity towards glucose CC (PubMed:12732097). {ECO:0000269|PubMed:12732097, CC ECO:0000269|PubMed:18087047, ECO:0000269|PubMed:19013440, CC ECO:0000269|PubMed:19563777, ECO:0000269|PubMed:9565553}. 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:12732097, CC ECO:0000269|PubMed:18087047}; 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:12732097, ECO:0000269|PubMed:18087047}; CC -!- CATALYTIC ACTIVITY: CC Reaction=13-cis-retinol + NADP(+) = 13-cis-retinal + H(+) + NADPH; CC Xref=Rhea:RHEA:54920, ChEBI:CHEBI:15378, ChEBI:CHEBI:45479, CC ChEBI:CHEBI:45487, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000269|PubMed:12732097}; CC -!- CATALYTIC ACTIVITY: CC Reaction=allyl alcohol + NADP(+) = acrolein + H(+) + NADPH; CC Xref=Rhea:RHEA:12168, ChEBI:CHEBI:15368, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16605, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.54; CC Evidence={ECO:0000269|PubMed:19563777}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(E)-4-hydroxynon-2-en-1-ol + NADP(+) = (E)-4-hydroxynon-2-enal CC + H(+) + NADPH; Xref=Rhea:RHEA:58416, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:58968, CC ChEBI:CHEBI:142617; Evidence={ECO:0000269|PubMed:19013440}; 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:0000269|PubMed:19563777}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NADP(+) + prenol = 3-methyl-2-butenal + H(+) + NADPH; CC Xref=Rhea:RHEA:58420, ChEBI:CHEBI:15378, ChEBI:CHEBI:15825, CC ChEBI:CHEBI:16019, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000269|PubMed:19563777}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(E)-hex-2-en-1-ol + NADP(+) = (E)-hex-2-enal + H(+) + NADPH; CC Xref=Rhea:RHEA:58424, ChEBI:CHEBI:15378, ChEBI:CHEBI:28913, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:141205; CC Evidence={ECO:0000269|PubMed:19563777}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(E,E)-2,4-hexadien-1-ol + NADP(+) = (E,E)-2,4-hexadienal + CC H(+) + NADPH; Xref=Rhea:RHEA:58428, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:82334, CC ChEBI:CHEBI:142625; Evidence={ECO:0000269|PubMed:19563777}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(E)-4-oxonon-2-en-1-ol + NADP(+) = (E)-4-oxonon-2-enal + H(+) CC + NADPH; Xref=Rhea:RHEA:58432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:58972, ChEBI:CHEBI:142624; CC Evidence={ECO:0000269|PubMed:19013440}; CC -!- CATALYTIC ACTIVITY: CC Reaction=4-methylpentan-1-ol + NADP(+) = 4-methylpentanal + H(+) + CC NADPH; Xref=Rhea:RHEA:58436, ChEBI:CHEBI:15378, ChEBI:CHEBI:17998, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:63910; CC Evidence={ECO:0000269|PubMed:19013440}; CC -!- ACTIVITY REGULATION: Retinaldehyde reductase activity is inhibited by CC tolrestat. {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:18087047}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=6000 uM for D,L-glyceraldehyde {ECO:0000269|PubMed:18087047}; CC KM=0.6 uM for all-trans-retinal {ECO:0000269|PubMed:18087047}; CC KM=0.7 uM for 9-cis-retinal {ECO:0000269|PubMed:18087047}; CC KM=37 uM for pyridine-3-aldehyde {ECO:0000269|PubMed:12732097}; CC KM=110 uM for acrolein {ECO:0000269|PubMed:19563777}; CC KM=87 uM for 3-methyl-2-butenal {ECO:0000269|PubMed:19563777}; CC KM=30 uM for 4-hydroxynonenal {ECO:0000269|PubMed:19563777}; CC KM=61 uM for (E)-2-hexenal {ECO:0000269|PubMed:19563777}; CC KM=95 uM for (E,E)-2,4-hexadienal {ECO:0000269|PubMed:19563777}; CC KM=532 uM for GS-acrolein {ECO:0000269|PubMed:19563777}; CC KM=245 uM for GS-3-methyl-2-butenal {ECO:0000269|PubMed:19563777}; CC KM=145 uM for GS-(E)-2-hexenal {ECO:0000269|PubMed:19563777}; CC KM=77 uM for GS-(E,E)-2,4-hexadienal {ECO:0000269|PubMed:19563777}; CC KM=330 uM for (E)-4-hydroxynon-2-enal {ECO:0000269|PubMed:19013440}; CC KM=300 uM for (E)-4-oxonon-2-enal {ECO:0000269|PubMed:19013440}; CC KM=50 uM for 4-methylpentanal {ECO:0000269|PubMed:19013440}; CC Vmax=3122 nmol/min/mg enzyme with acrolein CC {ECO:0000269|PubMed:19563777}; CC Vmax=2647 nmol/min/mg enzyme with 3-methyl-2-butenal as substrate CC {ECO:0000269|PubMed:19563777}; CC Vmax=2658 nmol/min/mg enzyme with (E)-2-hexenal as substrate CC {ECO:0000269|PubMed:19563777}; CC Vmax=2160 nmol/min/mg enzyme with (E,E)-2,4-hexadienal as substrate CC {ECO:0000269|PubMed:19563777}; CC Vmax=3298 nmol/min/mg enzyme with 4-hydroxynonenal CC {ECO:0000269|PubMed:19563777}; CC Vmax=64 nmol/min/mg enzyme with GS-acrolein CC {ECO:0000269|PubMed:19563777}; CC Vmax=1960 nmol/min/mg enzyme with GS-3-methyl-2-butenal as substrate CC {ECO:0000269|PubMed:19563777}; CC Vmax=2049 nmol/min/mg enzyme with GS-(E)-2-hexenal CC {ECO:0000269|PubMed:19563777}; CC Vmax=4004 nmol/min/mg enzyme with GS-(E,E)-2,4-hexadienal as CC substrate {ECO:0000269|PubMed:19563777}; CC Note=kcat is 640 min(-1) for glyceraldehyde as substrate CC (PubMed:12732097). kcat is 185 min(-1) for pyridine-3-aldehyde as CC substrate (PubMed:12732097). kcat is 116 min(-1) for acrolein as CC substrate. kcat is 103 min(-1) for 3-methyl-2-butenal as substrate. CC kcat is 97 min(-1) for(E)-2-hexenal as substrate. kcat is 82 min(-1) CC for (E,E)-2,4-hexadienal as substrate. kcat is 120 min(-1) for CC 4-hydroxynonenal as substrate. kcat is 3 min(-1) for GS-acrolein as CC substrate. kcat is 70 min(-1) for GS-3-methyl-2-butenal as substrate. CC kcat is 71 min(-1) for GS-(E)-2-hexenal as substrate. kcat is 147 CC min(-1) for (E,E)-2,4-hexadienal as substrate (PubMed:19563777). kcat CC is 35 min(-1) for D,L-glyceraldehyde as substrate. kcat is 27 min(-1) CC for all-trans-retinal as substrate. kcat is 1 min(-1) for CC 9-cis-retinal as substrate (PubMed:18087047). kcat is 43 min(-1) for CC 4-hydroxynon-2-enal (PubMed:19013440). kcat is 40 min(-1) for CC (E)-4-oxonon-2-enal (PubMed:19013440). kcat is 25 min(-1) for CC 4-methylpentanal (PubMed:19013440). {ECO:0000269|PubMed:12732097, CC ECO:0000269|PubMed:18087047, ECO:0000269|PubMed:19013440, CC ECO:0000269|PubMed:19563777}; CC -!- PATHWAY: Cofactor metabolism; retinol metabolism. CC {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:18087047}. CC -!- INTERACTION: CC O60218; Q13085: ACACA; NbExp=4; IntAct=EBI-1572139, EBI-717681; CC O60218; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-1572139, EBI-750109; CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:21585341}. Secreted CC {ECO:0000269|PubMed:21585341}. Note=Secreted through a lysosome- CC mediated non-classical pathway. CC -!- TISSUE SPECIFICITY: Found in many tissues. Highly expressed in small CC intestine, colon and adrenal gland. {ECO:0000269|PubMed:9565553}. CC -!- INDUCTION: Overexpressed in certain types of cancers, including CC hepatocellular carcinoma and lung cancer associated with tobacco CC smoking. {ECO:0000269|PubMed:15755999, ECO:0000269|PubMed:9565553}. CC -!- MISCELLANEOUS: Has no counterpart in murine and rat species. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U37100; AAC17469.1; -; mRNA. DR EMBL; AF052577; AAC36465.1; -; mRNA. DR EMBL; AF524864; AAO13380.1; -; mRNA. DR EMBL; BT006794; AAP35440.1; -; mRNA. DR EMBL; CR541801; CAG46600.1; -; mRNA. DR EMBL; AC078847; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH236950; EAL24069.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83816.1; -; Genomic_DNA. DR EMBL; BC008837; AAH08837.1; -; mRNA. DR EMBL; AF044961; AAC15671.1; -; mRNA. DR CCDS; CCDS5832.1; -. DR RefSeq; NP_064695.3; NM_020299.4. DR PDB; 1ZUA; X-ray; 1.25 A; X=1-316. DR PDB; 4GA8; X-ray; 1.94 A; A=1-316. DR PDB; 4GAB; X-ray; 1.60 A; A=1-316. DR PDB; 4GQ0; X-ray; 2.10 A; A=1-316. DR PDB; 4GQG; X-ray; 1.92 A; A=1-316. DR PDB; 4I5X; X-ray; 2.10 A; A=1-316. DR PDB; 4ICC; X-ray; 1.75 A; X=1-316. DR PDB; 4JIH; X-ray; 2.30 A; A=1-316. DR PDB; 4JII; X-ray; 2.20 A; X=1-316. DR PDB; 4WEV; X-ray; 1.45 A; X=1-316. DR PDB; 4XZL; X-ray; 1.70 A; X=1-316. DR PDB; 4XZM; X-ray; 1.75 A; X=1-316. DR PDB; 4XZN; X-ray; 1.70 A; X=1-316. DR PDB; 5LIK; X-ray; 2.05 A; X=1-316. DR PDB; 5LIU; X-ray; 1.75 A; X=1-316. DR PDB; 5LIW; X-ray; 1.75 A; X=1-316. DR PDB; 5LIX; X-ray; 1.95 A; X=1-316. DR PDB; 5LIY; X-ray; 2.05 A; X=1-316. DR PDB; 5M2F; X-ray; 1.50 A; X=1-316. DR PDB; 5Y7N; X-ray; 2.50 A; A=1-316. DR PDBsum; 1ZUA; -. DR PDBsum; 4GA8; -. DR PDBsum; 4GAB; -. DR PDBsum; 4GQ0; -. DR PDBsum; 4GQG; -. DR PDBsum; 4I5X; -. DR PDBsum; 4ICC; -. DR PDBsum; 4JIH; -. DR PDBsum; 4JII; -. DR PDBsum; 4WEV; -. DR PDBsum; 4XZL; -. DR PDBsum; 4XZM; -. DR PDBsum; 4XZN; -. DR PDBsum; 5LIK; -. DR PDBsum; 5LIU; -. DR PDBsum; 5LIW; -. DR PDBsum; 5LIX; -. DR PDBsum; 5LIY; -. DR PDBsum; 5M2F; -. DR PDBsum; 5Y7N; -. DR AlphaFoldDB; O60218; -. DR SMR; O60218; -. DR BioGRID; 121325; 57. DR IntAct; O60218; 17. DR MINT; O60218; -. DR STRING; 9606.ENSP00000352584; -. DR BindingDB; O60218; -. DR ChEMBL; CHEMBL5983; -. DR DrugBank; DB06246; Exisulind. DR DrugBank; DB02021; Fidarestat. DR DrugBank; DB06077; Lumateperone. DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate. DR DrugBank; DB00605; Sulindac. DR DrugBank; DB02383; Tolrestat. DR DrugBank; DB08772; Zopolrestat. DR DrugCentral; O60218; -. DR SwissLipids; SLP:000001873; -. DR GlyGen; O60218; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O60218; -. DR PhosphoSitePlus; O60218; -. DR BioMuta; AKR1B10; -. DR DOSAC-COBS-2DPAGE; O60218; -. DR EPD; O60218; -. DR jPOST; O60218; -. DR MassIVE; O60218; -. DR MaxQB; O60218; -. DR PaxDb; 9606-ENSP00000352584; -. DR PeptideAtlas; O60218; -. DR PRIDE; O60218; -. DR ProteomicsDB; 49247; -. DR Antibodypedia; 18084; 406 antibodies from 34 providers. DR DNASU; 57016; -. DR Ensembl; ENST00000359579.5; ENSP00000352584.4; ENSG00000198074.10. DR GeneID; 57016; -. DR KEGG; hsa:57016; -. DR MANE-Select; ENST00000359579.5; ENSP00000352584.4; NM_020299.5; NP_064695.3. DR UCSC; uc003vrr.4; human. DR AGR; HGNC:382; -. DR CTD; 57016; -. DR DisGeNET; 57016; -. DR GeneCards; AKR1B10; -. DR HGNC; HGNC:382; AKR1B10. DR HPA; ENSG00000198074; Tissue enhanced (esophagus, intestine, stomach). DR MIM; 604707; gene. DR neXtProt; NX_O60218; -. DR OpenTargets; ENSG00000198074; -. DR PharmGKB; PA24676; -. DR VEuPathDB; HostDB:ENSG00000198074; -. DR eggNOG; KOG1577; Eukaryota. DR GeneTree; ENSGT00940000154773; -. DR HOGENOM; CLU_023205_0_0_1; -. DR InParanoid; O60218; -. DR OMA; TWHHRVQ; -. DR OrthoDB; 890110at2759; -. DR PhylomeDB; O60218; -. DR TreeFam; TF106492; -. DR BRENDA; 1.1.1.21; 2681. DR PathwayCommons; O60218; -. DR Reactome; R-HSA-975634; Retinoid metabolism and transport. DR SABIO-RK; O60218; -. DR SignaLink; O60218; -. DR UniPathway; UPA00912; -. DR BioGRID-ORCS; 57016; 9 hits in 1111 CRISPR screens. DR ChiTaRS; AKR1B10; human. DR EvolutionaryTrace; O60218; -. DR GeneWiki; AKR1B10; -. DR GenomeRNAi; 57016; -. DR Pharos; O60218; Tchem. DR PRO; PR:O60218; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; O60218; Protein. DR Bgee; ENSG00000198074; Expressed in jejunal mucosa and 137 other cell types or tissues. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0008106; F:alcohol dehydrogenase (NADP+) activity; IDA:UniProtKB. DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IBA:GO_Central. DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; TAS:UniProtKB. DR GO; GO:0047655; F:allyl-alcohol dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0045550; F:geranylgeranyl reductase activity; IDA:UniProtKB. DR GO; GO:0047718; F:indanol dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0001758; F:retinal dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0110095; P:cellular detoxification of aldehyde; IDA:UniProtKB. DR GO; GO:0044597; P:daunorubicin metabolic process; IMP:UniProtKB. DR GO; GO:0044598; P:doxorubicin metabolic process; IMP:UniProtKB. DR GO; GO:0016488; P:farnesol catabolic process; IDA:UniProtKB. DR GO; GO:0001523; P:retinoid metabolic process; IDA:UniProtKB. DR CDD; cd19107; AKR_AKR1B1-19; 1. DR Gene3D; 3.20.20.100; NADP-dependent oxidoreductase domain; 1. DR InterPro; IPR020471; AKR. DR InterPro; IPR018170; Aldo/ket_reductase_CS. DR InterPro; IPR023210; NADP_OxRdtase_dom. DR InterPro; IPR036812; NADP_OxRdtase_dom_sf. DR PANTHER; PTHR11732:SF278; ALDO-KETO REDUCTASE FAMILY 1 MEMBER B10; 1. DR PANTHER; PTHR11732; ALDO/KETO REDUCTASE; 1. DR Pfam; PF00248; Aldo_ket_red; 1. DR PIRSF; PIRSF000097; AKR; 1. DR PRINTS; PR00069; ALDKETRDTASE. DR SUPFAM; SSF51430; NAD(P)-linked oxidoreductase; 1. DR PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1. DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1. DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1. DR Genevisible; O60218; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Lipid metabolism; Lysosome; NADP; KW Oxidoreductase; Reference proteome; Secreted. FT CHAIN 1..316 FT /note="Aldo-keto reductase family 1 member B10" FT /id="PRO_0000124632" FT ACT_SITE 49 FT /note="Proton donor" FT /evidence="ECO:0000269|PubMed:18087047" FT BINDING 20..22 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:18087047" FT BINDING 44 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:18087047" FT BINDING 111 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:18087047" FT BINDING 160..161 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:18087047" FT BINDING 184 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:18087047" FT BINDING 210..217 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:18087047" FT BINDING 261..273 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:18087047" FT SITE 78 FT /note="Lowers pKa of active site Tyr" FT /evidence="ECO:0000250|UniProtKB:P14550" FT MOD_RES 125 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 263 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VARIANT 87 FT /note="P -> S (in dbSNP:rs2303312)" FT /id="VAR_020077" FT VARIANT 286 FT /note="M -> T (in dbSNP:rs3735042)" FT /id="VAR_020078" FT VARIANT 313 FT /note="N -> D (in dbSNP:rs4728329)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9537432, ECO:0000269|PubMed:9565553, FT ECO:0000269|Ref.3, ECO:0000269|Ref.4, ECO:0000269|Ref.5, FT ECO:0007744|PubMed:21269460" FT /id="VAR_013287" FT MUTAGEN 125 FT /note="K->L: Increased affinity and reduced catalytic FT activity towards all-trans-retinaldehyde." FT /evidence="ECO:0000269|PubMed:18087047" FT MUTAGEN 299 FT /note="C->S: Decreased affinity and reduced catalytic FT activity towards 4-hydroxynonenal." FT /evidence="ECO:0000269|PubMed:19013440" FT MUTAGEN 301 FT /note="V->L: Reduced catalytic activity towards FT all-trans-retinaldehyde." FT /evidence="ECO:0000269|PubMed:18087047" FT CONFLICT 76 FT /note="V -> A (in Ref. 3; AAO13380)" FT /evidence="ECO:0000305" FT CONFLICT 100 FT /note="L -> P (in Ref. 3; AAO13380)" FT /evidence="ECO:0000305" FT CONFLICT 288 FT /note="T -> I (in Ref. 3; AAO13380)" FT /evidence="ECO:0000305" FT STRAND 4..6 FT /evidence="ECO:0007829|PDB:1ZUA" FT TURN 8..10 FT /evidence="ECO:0007829|PDB:5Y7N" FT STRAND 12..19 FT /evidence="ECO:0007829|PDB:1ZUA" FT TURN 25..27 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 28..37 FT /evidence="ECO:0007829|PDB:1ZUA" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 47..49 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 52..64 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 70..72 FT /evidence="ECO:0007829|PDB:1ZUA" FT STRAND 74..79 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 81..83 FT /evidence="ECO:0007829|PDB:4WEV" FT HELIX 86..100 FT /evidence="ECO:0007829|PDB:1ZUA" FT STRAND 105..111 FT /evidence="ECO:0007829|PDB:1ZUA" FT STRAND 118..120 FT /evidence="ECO:0007829|PDB:4WEV" FT STRAND 127..131 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 138..150 FT /evidence="ECO:0007829|PDB:1ZUA" FT STRAND 153..161 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 164..171 FT /evidence="ECO:0007829|PDB:1ZUA" FT STRAND 181..186 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 194..202 FT /evidence="ECO:0007829|PDB:1ZUA" FT STRAND 206..211 FT /evidence="ECO:0007829|PDB:1ZUA" FT STRAND 223..225 FT /evidence="ECO:0007829|PDB:5Y7N" FT HELIX 228..230 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 232..240 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 245..254 FT /evidence="ECO:0007829|PDB:1ZUA" FT TURN 255..257 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 267..274 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 283..290 FT /evidence="ECO:0007829|PDB:1ZUA" FT HELIX 302..304 FT /evidence="ECO:0007829|PDB:1ZUA" FT STRAND 305..307 FT /evidence="ECO:0007829|PDB:4GAB" FT HELIX 311..313 FT /evidence="ECO:0007829|PDB:4GAB" SQ SEQUENCE 316 AA; 36020 MW; 0C2FC0E798955A33 CRC64; MATFVELSTK AKMPIVGLGT WKSPLGKVKE AVKVAIDAGY RHIDCAYVYQ NEHEVGEAIQ EKIQEKAVKR EDLFIVSKLW PTFFERPLVR KAFEKTLKDL KLSYLDVYLI HWPQGFKSGD DLFPKDDKGN AIGGKATFLD AWEAMEELVD EGLVKALGVS NFSHFQIEKL LNKPGLKYKP VTNQVECHPY LTQEKLIQYC HSKGITVTAY SPLGSPDRPW AKPEDPSLLE DPKIKEIAAK HKKTAAQVLI RFHIQRNVIV IPKSVTPARI VENIQVFDFK LSDEEMATIL SFNRNWRACN VLQSSHLEDY PFNAEY //