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O43488 (ARK72_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. 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:
Aflatoxin B1 aldehyde reductase member 2

EC=1.1.1.n11
Alternative name(s):
AFB1 aldehyde reductase 1
Short name=AFB1-AR 1
Aldoketoreductase 7
Succinic semialdehyde reductase
Short name=SSA reductase
Gene names
Name:AKR7A2
Synonyms:AFAR, AFAR1, AKR7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length359 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Has NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen. Ref.3 Ref.9

Catalytic activity

4-hydroxybutanoate + NADP+ = succinate semialdehyde + NADPH. Ref.7

Subunit structure

Homodimer. Ref.3

Subcellular location

Golgi apparatus By similarity. Cytoplasm Ref.3.

Tissue specificity

Detected in brain, liver, small intestine and testis, and at lower levels in heart, prostate, skeletal muscle and spleen. Detected in kidney proximal and distal tubules, endothelial cells lining the Bowman's capsules and some cysts. Detected at low levels in lung and pancreas (at protein level). Widely expressed. Ref.3 Ref.7

Sequence similarities

Belongs to the aldo/keto reductase family. Aldo/keto reductase 2 subfamily.

Caution

It is uncertain whether Met-1 or Met-30 is the initiator.

Biophysicochemical properties

Kinetic parameters:

KM=20 µM for succinic semialdehyde Ref.7

KM=17 µM for 2-carboxybenzaldehyde

KM=8 µM for 9,10-phenanthrenequinone

KM=102 µM for 1,2-naphthoquinone

Sequence caution

The sequence AAC52104.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH04111.3 differs from that shown. Reason: Erroneous initiation.

The sequence AAH10852.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH11586.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH12171.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH13996.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAP36011.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAA76347.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAB72321.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 359359Aflatoxin B1 aldehyde reductase member 2
PRO_0000070375

Regions

Nucleotide binding171 – 1722NADP
Nucleotide binding226 – 23611NADP
Nucleotide binding318 – 3269NADP

Sites

Active site771Proton donor By similarity
Binding site721NADP
Binding site1411Substrate By similarity
Binding site1971NADP
Binding site2501NADP
Binding site2601Substrate By similarity
Binding site2631Substrate By similarity
Binding site3591Substrate By similarity
Site1051Lowers pKa of active site Tyr By similarity

Amino acid modifications

Modified residue1281N6-acetyllysine By similarity
Modified residue2361N6-succinyllysine By similarity

Natural variations

Natural variant1351V → M.
Corresponds to variant rs6670759 [ dbSNP | Ensembl ].
VAR_048209
Natural variant1421A → T. Ref.3 Ref.12
Corresponds to variant rs1043657 [ dbSNP | Ensembl ].
VAR_017413
Natural variant1571Q → H. Ref.12
Corresponds to variant rs859208 [ dbSNP | Ensembl ].
VAR_017414
Natural variant1801E → K.
Corresponds to variant rs859210 [ dbSNP | Ensembl ].
VAR_060222
Natural variant1981G → S.
Corresponds to variant rs2231200 [ dbSNP | Ensembl ].
VAR_048210
Natural variant2141C → Y.
Corresponds to variant rs2235794 [ dbSNP | Ensembl ].
VAR_017415
Natural variant2551S → N.
Corresponds to variant rs2231203 [ dbSNP | Ensembl ].
VAR_048211

Secondary structure

....................................................... 359
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43488 [UniParc].

Last modified November 14, 2003. Version 3.
Checksum: 2C9775FE4B977D2A

FASTA35939,589
        10         20         30         40         50         60 
MLSAASRVVS RAAVHCALRS PPPEARALAM SRPPPPRVAS VLGTMEMGRR MDAPASAAAV 

        70         80         90        100        110        120 
RAFLERGHTE LDTAFMYSDG QSETILGGLG LGLGGGDCRV KIATKANPWD GKSLKPDSVR 

       130        140        150        160        170        180 
SQLETSLKRL QCPQVDLFYL HAPDHGTPVE ETLHACQRLH QEGKFVELGL SNYASWEVAE 

       190        200        210        220        230        240 
ICTLCKSNGW ILPTVYQGMY NATTRQVETE LFPCLRHFGL RFYAYNPLAG GLLTGKYKYE 

       250        260        270        280        290        300 
DKDGKQPVGR FFGNSWAETY RNRFWKEHHF EAIALVEKAL QAAYGASAPS VTSAALRWMY 

       310        320        330        340        350 
HHSQLQGAHG DAVILGMSSL EQLEQNLAAT EEGPLEPAVV DAFNQAWHLV AHECPNYFR 

« Hide

References

« Hide 'large scale' references
[1]"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].
[2]"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] OF 2-359.
Tissue: Pancreas, Skin and Uterus.
[3]"Molecular cloning, expression and catalytic activity of a human AKR7 member of the aldo-keto reductase superfamily: evidence that the major 2-carboxybenzaldehyde reductase from human liver is a homologue of rat aflatoxin B1-aldehyde reductase."
Ireland L.S., Harrison D.J., Neal G.E., Hayes J.D.
Biochem. J. 332:21-34(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-359, PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT THR-142.
Tissue: Liver.
[4]"Cloning of the human aflatoxin B1-aldehyde reductase gene at 1p35-1p36.1 in a region frequently altered in human tumor cells."
Praml C., Savelyeva L., Perri P., Schwab M.
Cancer Res. 58:5014-5018(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-359.
Tissue: Brain.
[5]"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] OF 30-359.
[6]Lubec G., Vishwanath V.
Submitted (MAR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 222-236; 251-261 AND 279-297, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Brain and Cajal-Retzius cell.
[7]"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: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
[8]"Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct subclass of aldo-keto reductase 7 family proteins."
Kelly V.P., Sherratt P.J., Crouch D.H., Hayes J.D.
Biochem. J. 366:847-861(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GENE STRUCTURE.
[9]"Synthesis and catabolism of gamma-hydroxybutyrate in SH-SY5Y human neuroblastoma cells: role of the aldo-keto reductase AKR7A2."
Lyon R.C., Johnston S.M., Watson D.G., McGarvie G., Ellis E.M.
J. Biol. Chem. 282:25986-25992(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"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].
[11]"Structure of the aflatoxin aldehyde reductase in complex with NADPH."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NADP.
[12]"Genetic variation of aflatoxin B1 aldehyde reductase genes (AFAR) in human tumour cells."
Praml C., Schulz W., Claas A., Mollenhauer J., Poustka A., Ackermann R., Schwab M., Henrich K.-O.
Cancer Lett. 272:160-166(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-142 AND HIS-157.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL035413 Genomic DNA. Translation: CAB72321.1. Different initiation.
BC004111 mRNA. Translation: AAH04111.3. Different initiation.
BC007352 mRNA. Translation: AAH07352.2.
BC010852 mRNA. Translation: AAH10852.1. Different initiation.
BC011586 mRNA. Translation: AAH11586.1. Different initiation.
BC012171 mRNA. Translation: AAH12171.1. Different initiation.
BC013996 mRNA. Translation: AAH13996.1. Different initiation.
AF026947 mRNA. Translation: AAC52104.1. Different initiation.
Y16675 mRNA. Translation: CAA76347.1. Different initiation.
BT007347 mRNA. Translation: AAP36011.1. Different initiation.
BK000395 mRNA. Translation: DAA00088.1.
CCDSCCDS194.1.
RefSeqNP_003680.2. NM_003689.3.
UniGeneHs.571886.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BP1X-ray2.40A/B/C/D30-359[»]
ProteinModelPortalO43488.
SMRO43488. Positions 37-359.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114142. 6 interactions.
IntActO43488. 2 interactions.
MINTMINT-5002225.
STRING9606.ENSP00000235835.

PTM databases

PhosphoSiteO43488.

2D gel databases

REPRODUCTION-2DPAGEIPI00305978.
O43488.
UCD-2DPAGEO43488.

Proteomic databases

MaxQBO43488.
PaxDbO43488.
PRIDEO43488.

Protocols and materials databases

DNASU8574.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000235835; ENSP00000235835; ENSG00000053371.
GeneID8574.
KEGGhsa:8574.
UCSCuc001bbw.3. human.

Organism-specific databases

CTD8574.
GeneCardsGC01M019630.
H-InvDBHIX0000198.
HGNCHGNC:389. AKR7A2.
HPACAB032587.
CAB032841.
MIM603418. gene.
neXtProtNX_O43488.
PharmGKBPA24682.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0667.
HOGENOMHOG000250286.
HOVERGENHBG050576.
InParanoidO43488.
KOK15303.
OMACTVKIAT.
OrthoDBEOG77127F.
PhylomeDBO43488.
TreeFamTF329173.

Enzyme and pathway databases

SABIO-RKO43488.

Gene expression databases

ArrayExpressO43488.
BgeeO43488.
CleanExHS_AKR7A2.
GenevestigatorO43488.

Family and domain databases

Gene3D3.20.20.100. 1 hit.
InterProIPR001395. Aldo/ket_red.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERPTHR11732. PTHR11732. 1 hit.
PfamPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
SUPFAMSSF51430. SSF51430. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceO43488.
GeneWikiAKR7A2.
GenomeRNAi8574.
NextBio32161.
PMAP-CutDBO43488.
PROO43488.
SOURCESearch...

Entry information

Entry nameARK72_HUMAN
AccessionPrimary (citable) accession number: O43488
Secondary accession number(s): O75749, Q5TG63
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 14, 2003
Last modified: July 9, 2014
This is version 139 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