O60218 (AK1BA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	316 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Lysosome Secreted
Coding sequence diversity	Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular 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_component	cytosol Traceable author statement. Source: Reactome extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	aldo-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
ACACA	Q13085	4	EBI-1572139,EBI-717681

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 316

316

Aldo-keto reductase family 1 member B10

PRO_0000124632

Regions

Nucleotide binding

20 – 22

3

NADP

Nucleotide binding

160 – 161

2

NADP

Nucleotide binding

210 – 217

8

NADP

Nucleotide binding

261 – 273

13

NADP

Sites

Active site

49

1

Proton donor

Binding site

44

1

NADP

Binding site

111

1

Substrate

Binding site

184

1

NADP

Site

78

1

Lowers pKa of active site Tyr By similarity

Amino acid modifications

Modified residue

125

1

N6-acetyllysine Ref.11

Modified residue

263

1

N6-acetyllysine Ref.11

Natural variations

Natural variant

87

1

P → S.
Corresponds to variant rs2303312 [ dbSNP | Ensembl ].

VAR_020077

Natural variant

286

1

M → T.
Corresponds to variant rs3735042 [ dbSNP | Ensembl ].

VAR_020078

Natural variant

313

1

N → 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

Mutagenesis

125

1

K → L: Increased affinity and reduced catalytic activity towards all-trans-retinaldehyde. Ref.13

Mutagenesis

301

1

V → L: Reduced catalytic activity towards all-trans-retinaldehyde. Ref.13

Sequence conflict

76

1

V → A in AAO13380. Ref.3

Sequence conflict

100

1

L → P in AAO13380. Ref.3

Sequence conflict

288

1

T → I in AAO13380. Ref.3

Secondary structure

1

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316

Helix Strand Turn

Details...

Beta strand

4 – 6

3

Beta strand

12 – 19

8

Turn

25 – 27

3

Helix

28 – 37

10

Beta strand

42 – 44

3

Helix

47 – 49

3

Helix

52 – 64

13

Helix

70 – 72

3

Beta strand

74 – 79

6

Helix

86 – 100

15

Beta strand

105 – 111

7

Beta strand

127 – 131

5

Helix

138 – 150

13

Beta strand

153 – 161

9

Helix

164 – 171

8

Beta strand

181 – 186

6

Helix

194 – 202

9

Beta strand

206 – 211

6

Helix

228 – 230

3

Helix

232 – 240

9

Helix

245 – 254

10

Turn

255 – 257

3

Helix

267 – 274

8

Helix

283 – 290

8

Helix

302 – 304

3

Sequences

	Sequence		Length	Mass (Da)
	O60218 [UniParc]. Last modified February 8, 2011. Version 2. Checksum: 0C2FC0E798955A33	FASTA	316	36,020
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY.
+	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.

IPI

IPI00105407.

RefSeq

NP_064695.3. NM_020299.4.

UniGene

Hs.116724.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZUA	X-ray	1.25	X	1-316	[»]
4GAB	X-ray	1.60	A	1-316	[»]

ProteinModelPortal

O60218.

SMR

O60218. Positions 1-316.

ModBase

Search...

Protein-protein interaction databases

IntAct

O60218. 1 interaction.

STRING

9606.ENSP00000352584.

PTM databases

PhosphoSite

O60218.

2D gel databases

DOSAC-COBS-2DPAGE

O60218.

Proteomic databases

PaxDb

O60218.

PRIDE

O60218.

Protocols and materials databases

DNASU

57016.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000359579; ENSP00000352584; ENSG00000198074.

GeneID

57016.

KEGG

hsa:57016.

UCSC

uc003vrr.3. human.

Organism-specific databases

CTD

57016.

GeneCards

GC07P134212.

H-InvDB

HIX0007102.
HIX0033661.

HGNC

HGNC:382. AKR1B10.

HPA

HPA020280.

MIM

604707. gene.

neXtProt

NX_O60218.

PharmGKB

PA24676.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0656.

HOGENOM

HOG000250272.

HOVERGEN

HBG000020.

InParanoid

O60218.

KO

K00011.

OMA

GVSNFSH.

OrthoDB

EOG4VMFFR.

PhylomeDB

O60218.

Enzyme and pathway databases

SABIO-RK

O60218.

Gene expression databases

Bgee

O60218.

CleanEx

HS_AKR1B10.

Genevestigator

O60218.

GermOnline

ENSG00000198074. Homo sapiens.

Family and domain databases

Gene3D

3.20.20.100. 1 hit.

InterPro

IPR001395. Aldo/ket_red.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase_subgr.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]

PANTHER

PTHR11732. PTHR11732. 1 hit.

Pfam

PF00248. Aldo_ket_red. 1 hit.
[Graphical view]

PIRSF

PIRSF000097. AKR. 1 hit.

PRINTS

PR00069. ALDKETRDTASE.

SUPFAM

SSF51430. Aldo/ket_red. 1 hit.

PROSITE

PS00798. ALDOKETO_REDUCTASE_1. 1 hit.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O60218.

ChEMBL

CHEMBL5983.

EvolutionaryTrace

O60218.

GenomeRNAi

57016.

NextBio

62758.

SOURCE

Search...

Entry information

Entry name

AK1BA_HUMAN

Accession

Primary (citable) accession number: O60218
Secondary accession number(s): A4D1P1 , O75890, Q6FHF3, Q8IWZ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2002
Last sequence update:	February 8, 2011
Last modified:	May 29, 2013
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.