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O60218 (AK1BA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aldo-keto reductase family 1 member B10

EC=1.1.1.-
Alternative name(s):
ARL-1
Aldose reductase-like
Aldose reductase-related protein
Short name=ARP
Short name=hARP
Small intestine reductase
Short name=SI reductase
Gene names
Name:AKR1B10
Synonyms:AKR1B11
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length316 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs. Ref.13

Enzyme regulation

Inhibited by tolrestat. Ref.13

Subcellular location

Lysosome. Secreted. Note: Secreted through a lysosome-mediated non-classical pathway. Ref.12

Tissue specificity

Found in many tissues. Highly expressed in small intestine, colon and adrenal gland.

Sequence similarities

Belongs to the aldo/keto reductase family.

Biophysicochemical properties

Kinetic parameters:

KM=600 µM for D,L-glyceraldehyde Ref.13

KM=0.6 µM for all-trans-retinaldehyde

KM=0.7 µM for 9-cis-retinaldehyde

Ontologies

Keywords
   Cellular componentLysosome
Secreted
   Coding sequence diversityPolymorphism
   LigandNADP
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular aldehyde metabolic process

Traceable author statement Ref.1. Source: ProtInc

daunorubicin metabolic process

Inferred from mutant phenotype PubMed 20837989. Source: UniProtKB

digestion

Traceable author statement Ref.1. Source: ProtInc

doxorubicin metabolic process

Inferred from mutant phenotype PubMed 20837989. Source: UniProtKB

farnesol catabolic process

Inferred from direct assay PubMed 21187079. Source: UniProtKB

phototransduction, visible light

Traceable author statement. Source: Reactome

retinoid metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionaldo-keto reductase (NADP) activity

Traceable author statement Ref.1. Source: UniProtKB

geranylgeranyl reductase activity

Inferred from direct assay PubMed 21187079. Source: UniProtKB

indanol dehydrogenase activity

Inferred from direct assay PubMed 20837989. Source: UniProtKB

retinal dehydrogenase activity

Inferred from direct assay PubMed 21851338. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ACACAQ130854EBI-1572139,EBI-717681

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 316316Aldo-keto reductase family 1 member B10
PRO_0000124632

Regions

Nucleotide binding20 – 223NADP
Nucleotide binding160 – 1612NADP
Nucleotide binding210 – 2178NADP
Nucleotide binding261 – 27313NADP

Sites

Active site491Proton donor
Binding site441NADP
Binding site1111Substrate
Binding site1841NADP
Site781Lowers pKa of active site Tyr By similarity

Amino acid modifications

Modified residue1251N6-acetyllysine Ref.11
Modified residue2631N6-acetyllysine Ref.11

Natural variations

Natural variant871P → S.
Corresponds to variant rs2303312 [ dbSNP | Ensembl ].
VAR_020077
Natural variant2861M → T.
Corresponds to variant rs3735042 [ dbSNP | Ensembl ].
VAR_020078
Natural variant3131N → D. Ref.1 Ref.3 Ref.4 Ref.5 Ref.9 Ref.10 Ref.14
Corresponds to variant rs4728329 [ dbSNP | Ensembl ].
VAR_013287

Experimental info

Mutagenesis1251K → L: Increased affinity and reduced catalytic activity towards all-trans-retinaldehyde. Ref.13
Mutagenesis3011V → L: Reduced catalytic activity towards all-trans-retinaldehyde. Ref.13
Sequence conflict761V → A in AAO13380. Ref.3
Sequence conflict1001L → P in AAO13380. Ref.3
Sequence conflict2881T → I in AAO13380. Ref.3

Secondary structure

...................................................... 316
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O60218 [UniParc].

Last modified February 8, 2011. Version 2.
Checksum: 0C2FC0E798955A33

FASTA31636,020
        10         20         30         40         50         60 
MATFVELSTK AKMPIVGLGT WKSPLGKVKE AVKVAIDAGY RHIDCAYVYQ NEHEVGEAIQ 

        70         80         90        100        110        120 
EKIQEKAVKR EDLFIVSKLW PTFFERPLVR KAFEKTLKDL KLSYLDVYLI HWPQGFKSGD 

       130        140        150        160        170        180 
DLFPKDDKGN AIGGKATFLD AWEAMEELVD EGLVKALGVS NFSHFQIEKL LNKPGLKYKP 

       190        200        210        220        230        240 
VTNQVECHPY LTQEKLIQYC HSKGITVTAY SPLGSPDRPW AKPEDPSLLE DPKIKEIAAK 

       250        260        270        280        290        300 
HKKTAAQVLI RFHIQRNVIV IPKSVTPARI VENIQVFDFK LSDEEMATIL SFNRNWRACN 

       310 
VLQSSHLEDY PFNAEY 

« Hide

References

« Hide 'large scale' references
[1]"Identification and characterization of a novel human aldose reductase-like gene."
Cao D., Fan S.T., Chung S.S.M.
J. Biol. Chem. 273:11429-11435(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-313.
Tissue: Liver tumor.
[2]"Sequence and expression levels in human tissues of a new member of the aldo-keto reductase family."
Hyndman D.J., Flynn T.G.
Biochim. Biophys. Acta 1399:198-202(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Small intestine.
[3]"Representational difference analysis based identification and full-length sequencing of a gene of the aldo-ketoreductase family strongly overexpressed in hepatocellular carcinoma."
Heringlake S.
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-313.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASP-313.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASP-313.
[6]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASP-313.
Tissue: Pancreas.
[10]"New member of aldose reductase family proteins overexpressed in human hepatocellular carcinoma."
Scuric Z., Stain S.C., Anderson W.F., Hwang J.-J.
Hepatology 27:943-950(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 232-316, VARIANT ASP-313.
[11]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-125 AND LYS-263, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Aldo-keto reductase family 1, member B10 is secreted through a lysosome-mediated non-classical pathway."
Luo D.X., Huang M.C., Ma J., Gao Z., Liao D.F., Cao D.
Biochem. J. 438:71-80(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[13]"Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10."
Gallego O., Ruiz F.X., Ardevol A., Dominguez M., Alvarez R., de Lera A.R., Rovira C., Farres J., Fita I., Pares X.
Proc. Natl. Acad. Sci. U.S.A. 104:20764-20769(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH TOLRESTAT AND NADP, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, MUTAGENESIS OF LYS-125 AND VAL-301.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-313, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U37100 mRNA. Translation: AAC17469.1.
AF052577 mRNA. Translation: AAC36465.1.
AF524864 mRNA. Translation: AAO13380.1.
BT006794 mRNA. Translation: AAP35440.1.
CR541801 mRNA. Translation: CAG46600.1.
AC078847 Genomic DNA. No translation available.
CH236950 Genomic DNA. Translation: EAL24069.1.
CH471070 Genomic DNA. Translation: EAW83816.1.
BC008837 mRNA. Translation: AAH08837.1.
AF044961 mRNA. Translation: AAC15671.1.
RefSeqNP_064695.3. NM_020299.4.
UniGeneHs.116724.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZUAX-ray1.25X1-316[»]
4GA8X-ray1.94A1-316[»]
4GABX-ray1.60A1-316[»]
4GQ0X-ray2.10A1-316[»]
4GQGX-ray1.92A1-316[»]
4I5XX-ray2.10A1-316[»]
4ICCX-ray1.75X1-316[»]
4JIHX-ray2.30A1-316[»]
4JIIX-ray2.20X1-316[»]
ProteinModelPortalO60218.
SMRO60218. Positions 1-316.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121325. 3 interactions.
IntActO60218. 1 interaction.
STRING9606.ENSP00000352584.

Chemistry

BindingDBO60218.
ChEMBLCHEMBL5983.

PTM databases

PhosphoSiteO60218.

2D gel databases

DOSAC-COBS-2DPAGEO60218.

Proteomic databases

PaxDbO60218.
PRIDEO60218.

Protocols and materials databases

DNASU57016.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359579; ENSP00000352584; ENSG00000198074.
GeneID57016.
KEGGhsa:57016.
UCSCuc003vrr.3. human.

Organism-specific databases

CTD57016.
GeneCardsGC07P134212.
H-InvDBHIX0007102.
HIX0033661.
HGNCHGNC:382. AKR1B10.
HPAHPA020280.
MIM604707. gene.
neXtProtNX_O60218.
PharmGKBPA24676.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0656.
HOGENOMHOG000250272.
HOVERGENHBG000020.
InParanoidO60218.
KOK00011.
OMAYPFDAEY.
OrthoDBEOG70KGQF.
PhylomeDBO60218.
TreeFamTF106492.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SABIO-RKO60218.

Gene expression databases

BgeeO60218.
CleanExHS_AKR1B10.
GenevestigatorO60218.

Family and domain databases

Gene3D3.20.20.100. 1 hit.
InterProIPR001395. Aldo/ket_red.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase_subgr.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERPTHR11732. PTHR11732. 1 hit.
PfamPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
PIRSFPIRSF000097. AKR. 1 hit.
PRINTSPR00069. ALDKETRDTASE.
SUPFAMSSF51430. SSF51430. 1 hit.
PROSITEPS00798. ALDOKETO_REDUCTASE_1. 1 hit.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO60218.
GeneWikiAKR1B10.
GenomeRNAi57016.
NextBio62758.
PROO60218.
SOURCESearch...

Entry information

Entry nameAK1BA_HUMAN
AccessionPrimary (citable) accession number: O60218
Secondary accession number(s): A4D1P1 expand/collapse secondary AC list , O75890, Q6FHF3, Q8IWZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2002
Last sequence update: February 8, 2011
Last modified: April 16, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM