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P14550 (AK1A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 153. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alcohol dehydrogenase [NADP(+)]

EC=1.1.1.2
Alternative name(s):
Aldehyde reductase
Aldo-keto reductase family 1 member A1
Gene names
Name:AKR1A1
Synonyms:ALDR1, ALR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length325 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyde to glycerol. Has broad substrate specificity. In vitro substrates include succinic semialdehyde, 4-nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D-glucuronic acid. Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN). Ref.12 Ref.13 Ref.14

Catalytic activity

An alcohol + NADP+ = an aldehyde + NADPH.

Subunit structure

Monomer By similarity.

Tissue specificity

Widely expressed. Highly expressed in kidney, salivary gland and liver. Detected in trachea, stomach, brain, lung, prostate, placenta, mammary gland, small intestine and lung. Ref.12 Ref.13

Sequence similarities

Belongs to the aldo/keto reductase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10 Ref.15
Chain2 – 325324Alcohol dehydrogenase [NADP(+)]
PRO_0000124617

Regions

Nucleotide binding211 – 27363NADP By similarity

Sites

Active site501Proton donor
Binding site1131Substrate
Site801Lowers pKa of active site Tyr

Amino acid modifications

Modified residue21N-acetylalanine Ref.15
Modified residue1271N6-acetyllysine; alternate By similarity
Modified residue1271N6-succinyllysine; alternate By similarity
Modified residue1451N6-succinyllysine By similarity

Natural variations

Natural variant521N → S Reduced activity towards daunorubicin. Ref.14
Corresponds to variant rs2229540 [ dbSNP | Ensembl ].
VAR_048212
Natural variant551E → D Reduced activity towards daunorubicin. Ref.14
Corresponds to variant rs6690497 [ dbSNP | Ensembl ].
VAR_058909

Experimental info

Mutagenesis501Y → F: Complete loss of enzymatic activity. Ref.11
Mutagenesis501Y → H: Complete loss of enzymatic activity. Ref.11
Mutagenesis801K → M: Complete loss of enzymatic activity. Ref.11
Mutagenesis1131H → Q: Strong decrease in enzymatic activity. Ref.11
Mutagenesis2991I → A: No change in enzymatic activity. Ref.11
Mutagenesis2991I → C: No change in enzymatic activity. Ref.11
Mutagenesis3001V → C: No change in enzymatic activity. Ref.11
Sequence conflict3051V → A in BAF85772. Ref.4

Secondary structure

....................................................... 325
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P14550 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: F6B27517EB754E37

FASTA32536,573
        10         20         30         40         50         60 
MAASCVLLHT GQKMPLIGLG TWKSEPGQVK AAVKYALSVG YRHIDCAAIY GNEPEIGEAL 

        70         80         90        100        110        120 
KEDVGPGKAV PREELFVTSK LWNTKHHPED VEPALRKTLA DLQLEYLDLY LMHWPYAFER 

       130        140        150        160        170        180 
GDNPFPKNAD GTICYDSTHY KETWKALEAL VAKGLVQALG LSNFNSRQID DILSVASVRP 

       190        200        210        220        230        240 
AVLQVECHPY LAQNELIAHC QARGLEVTAY SPLGSSDRAW RDPDEPVLLE EPVVLALAEK 

       250        260        270        280        290        300 
YGRSPAQILL RWQVQRKVIC IPKSITPSRI LQNIKVFDFT FSPEEMKQLN ALNKNWRYIV 

       310        320 
PMLTVDGKRV PRDAGHPLYP FNDPY 

« Hide

References

« Hide 'large scale' references
[1]"The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases."
Bohren K.M., Bullock B., Wermuth B., Gabbay K.H.
J. Biol. Chem. 264:9547-9551(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.
[2]"The structural organization of the human aldehyde reductase gene, AKR1A1, and mapping to chromosome 1p33-->p32."
Fujii J., Hamaoka R., Matsumoto A., Fujii T., Yamaguchi Y., Egashira M., Miyoshi O., Niikawa N., Taniguchi N.
Cytogenet. Cell Genet. 84:230-232(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Characterization of the human aldehyde reductase gene and promoter."
Barski O.A., Gabbay K.H., Bohren K.M.
Genomics 60:188-198(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[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]"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [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 (SEP-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].
Tissue: Colon and Kidney.
[10]"Primary structure of aldehyde reductase from human liver."
Wermuth B., Omar A., Forster A., di Francesco C., Wolf M., von Wartburg J.-P., Bullock B., Gabbay K.H.
Prog. Clin. Biol. Res. 232:297-307(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-325.
Tissue: Liver.
[11]"Mechanism of human aldehyde reductase: characterization of the active site pocket."
Barski O.A., Gabbay K.H., Grimshaw C.E., Bohren K.M.
Biochemistry 34:11264-11275(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF TYR-50; LYS-80; HIS-113; ILE-299 AND VAL-300.
[12]"Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members."
O'Connor T., Ireland L.S., Harrison D.J., Hayes J.D.
Biochem. J. 343:487-504(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[13]"Metabolic activation of polycyclic aromatic hydrocarbon trans-dihydrodiols by ubiquitously expressed aldehyde reductase (AKR1A1)."
Palackal N.T., Burczynski M.E., Harvey R.G., Penning T.M.
Chem. Biol. Interact. 130:815-824(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[14]"Two allelic variants of aldo-keto reductase 1A1 exhibit reduced in vitro metabolism of daunorubicin."
Bains O.S., Takahashi R.H., Pfeifer T.A., Grigliatti T.A., Reid R.E., Riggs K.W.
Drug Metab. Dispos. 36:904-910(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS SER-52 AND ASP-55.
[15]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[16]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Structures of human and porcine aldehyde reductase: an enzyme implicated in diabetic complications."
El-Kabbani O., Green N.C., Lin G., Carson M., Narayana S.V.L., Moore K.M., Flynn T.G., DeLucas L.J.
Acta Crystallogr. D 50:859-868(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04794 mRNA. Translation: AAA51711.1.
AF036683 expand/collapse EMBL AC list , AF036680, AF036681, AF036682 Genomic DNA. Translation: AAB92369.1.
AF112485, AF112484 Genomic DNA. Translation: AAF01260.1.
AK293083 mRNA. Translation: BAF85772.1.
CR457010 mRNA. Translation: CAG33291.1.
BT007003 mRNA. Translation: AAP35649.1.
AL355480 Genomic DNA. Translation: CAI22459.1.
CH471059 Genomic DNA. Translation: EAX06970.1.
CH471059 Genomic DNA. Translation: EAX06971.1.
CH471059 Genomic DNA. Translation: EAX06972.1.
CH471059 Genomic DNA. Translation: EAX06974.1.
BC000670 mRNA. Translation: AAH00670.1.
BC005394 mRNA. Translation: AAH05394.1.
PIRA33851.
RefSeqNP_001189342.1. NM_001202413.1.
NP_001189343.1. NM_001202414.1.
NP_006057.1. NM_006066.3.
NP_697021.1. NM_153326.2.
UniGeneHs.474584.
Hs.721160.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ALRX-ray2.48A2-325[»]
ProteinModelPortalP14550.
SMRP14550. Positions 2-325.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115610. 4 interactions.
IntActP14550. 2 interactions.
MINTMINT-5001699.
STRING9606.ENSP00000312606.

Chemistry

BindingDBP14550.
ChEMBLCHEMBL2246.

PTM databases

PhosphoSiteP14550.

Polymorphism databases

DMDM113600.

2D gel databases

REPRODUCTION-2DPAGEIPI00220271.
P14550.
SWISS-2DPAGEP14550.
UCD-2DPAGEP14550.

Proteomic databases

PaxDbP14550.
PeptideAtlasP14550.
PRIDEP14550.

Protocols and materials databases

DNASU10327.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000351829; ENSP00000312606; ENSG00000117448.
ENST00000372070; ENSP00000361140; ENSG00000117448.
GeneID10327.
KEGGhsa:10327.
UCSCuc001cod.3. human.

Organism-specific databases

CTD10327.
GeneCardsGC01P046017.
HGNCHGNC:380. AKR1A1.
HPACAB006246.
HPA017919.
HPA019649.
HPA027734.
MIM103830. gene.
neXtProtNX_P14550.
PharmGKBPA24674.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0656.
HOGENOMHOG000250272.
HOVERGENHBG000020.
InParanoidP14550.
KOK00002.
OMAWPYAFER.
OrthoDBEOG70KGQF.
PhylomeDBP14550.
TreeFamTF106492.

Enzyme and pathway databases

SABIO-RKP14550.

Gene expression databases

ArrayExpressP14550.
BgeeP14550.
CleanExHS_AKR1A1.
GenevestigatorP14550.

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

ChiTaRSAKR1A1. human.
EvolutionaryTraceP14550.
GeneWikiAldo-keto_reductase_family_1,_member_A1.
GenomeRNAi10327.
NextBio39151.
PROP14550.
SOURCESearch...

Entry information

Entry nameAK1A1_HUMAN
AccessionPrimary (citable) accession number: P14550
Secondary accession number(s): A8KAL8, D3DQ04, Q6IAZ4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 153 of the entry and version 3 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 1

Human chromosome 1: entries, gene names and cross-references to MIM