AK1BA_HUMAN
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 03-AUG-2022, entry version 191.
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 4-
CC 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 9-cis-
CC retinal as substrate (PubMed:18087047). kcat is 43 min(-1) for 4-
CC hydroxynon-2-enal (PubMed:19013440). kcat is 40 min(-1) for (E)-4-
CC oxonon-2-enal (PubMed:19013440). kcat is 25 min(-1) for 4-
CC 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}.
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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; 48.
DR IntAct; O60218; 16.
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 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; O60218; -.
DR PeptideAtlas; O60218; -.
DR PRIDE; O60218; -.
DR ProteomicsDB; 49247; -.
DR Antibodypedia; 18084; 373 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 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; ECGEGVA; -.
DR OrthoDB; 1016440at2759; -.
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 1031 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 136 other tissues.
DR Genevisible; O60218; HS.
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 Gene3D; 3.20.20.100; -; 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 Pfam; PF00248; Aldo_ket_red; 1.
DR PIRSF; PIRSF000097; AKR; 1.
DR PRINTS; PR00069; ALDKETRDTASE.
DR SUPFAM; SSF51430; SSF51430; 1.
DR PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
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 all-trans-
FT 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
