Reviewed, UniProtKB/Swiss-Prot O60218 (AK1BA_HUMAN)

Names and origin

Protein names

Recommended name:
    Aldo-keto reductase family 1 member B10
    EC=1.1.1.-
Alternative name(s):
    Aldose reductase-like
    ARL-1
    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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	316 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.10
Enzyme regulation	Inhibited by tolrestat. Ref.10
Subcellular location	Cytoplasm Probable.
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 KM=0.6 µM for all-trans-retinaldehyde KM=0.7 µM for 9-cis-retinaldehyde

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cellular aldehyde metabolic process Ref.1 Traceable author statement. Source: ProtInc digestion Ref.1 Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW steroid metabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aldo-keto reductase activity Ref.1 Traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACACA	Q13085	3	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

Natural variations

Natural variant

87

1

P → S: dbSNP rs2303312.

VAR_020077

Natural variant

286

1

M → T: dbSNP rs3735042.

VAR_020078

Natural variant

313

1

D → N: dbSNP rs4728329. Ref.2 Ref.6 Ref.7

VAR_013287

Experimental info

Mutagenesis

125

1

K → L: Increased affinity and reduced catalytic activity towards all-trans-retinaldehyde. Ref.10

Mutagenesis

301

1

V → L: Reduced catalytic activity towards all-trans-retinaldehyde. Ref.10

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)
	O60218-1 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 0C2FC0E978955A33	FASTA	316	36,021
	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 PFDAEY

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: 9565553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 9765596] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-313. 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].
[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].
[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].
[6]	"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: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASN-313.
[7]	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], VARIANT ASN-313.
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[9]	"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: 9537432] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 232-316.
[10]	"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: 18087047] [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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
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.

UniGene

Hs.116724

3D structure databases

PDBPDBe

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

ModBase

Search...

Protein-protein interaction databases

IntAct

O60218. 1 interaction.

PTM databases

PhosphoSite

O60218.

2-D gel databases

DOSAC-COBS-2DPAGE

O60218.

Proteomic databases

PRIDE

O60218.

Genome annotation databases

Ensembl

ENSG00000198074. Homo sapiens. [Contig view]

GeneID

57016.

KEGG

hsa:57016.

NMPDR

fig|9606.3.peg.29472.

Organism-specific databases

GeneCards

GC07P133862.
GC07P133901.

H-InvDB

HIX0007102.
HIX0033661.

HGNC

HGNC:382. AKR1B10.

MIM

604707. gene.

PharmGKB

PA24676.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O60218.

HOVERGEN

O60218.

Gene expression databases

Bgee

O60218.

CleanEx

HS_AKR1B10.

GermOnline

ENSG00000198074. Homo sapiens.

Family and domain databases

InterPro

IPR001395. Aldo/ket_red.
IPR018170. Aldo/ket_reductase_CS.
[Graphical view]

Gene3D

G3DSA:3.20.20.100. Aldo/ket_red. 1 hit.

PANTHER

PTHR11732. Aldo/ket_red. 1 hit.

Pfam

PF00248. Aldo_ket_red. 1 hit.
[Graphical view]

ProDom

PD000288. Aldo/ket_red. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

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

ProtoNet

Search...

Other Resources

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:	August 1, 1998
Last modified:	June 16, 2009
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)