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O43488

- ARK72_HUMAN

UniProt

O43488 - ARK72_HUMAN

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Protein
Aflatoxin B1 aldehyde reductase member 2
Gene
AKR7A2, AFAR, AFAR1, AKR7
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

4-hydroxybutanoate + NADP+ = succinate semialdehyde + NADPH.1 Publication

Kineticsi

  1. KM=20 µM for succinic semialdehyde1 Publication
  2. KM=17 µM for 2-carboxybenzaldehyde
  3. KM=8 µM for 9,10-phenanthrenequinone
  4. KM=102 µM for 1,2-naphthoquinone

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei72 – 721NADP
Active sitei77 – 771Proton donor By similarity
Sitei105 – 1051Lowers pKa of active site Tyr By similarity
Binding sitei141 – 1411Substrate By similarity
Binding sitei197 – 1971NADP
Binding sitei250 – 2501NADP
Binding sitei260 – 2601Substrate By similarity
Binding sitei263 – 2631Substrate By similarity
Binding sitei359 – 3591Substrate By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi171 – 1722NADP
Nucleotide bindingi226 – 23611NADP
Add
BLAST
Nucleotide bindingi318 – 3269NADP

GO - Molecular functioni

  1. alditol:NADP+ 1-oxidoreductase activity Source: ProtInc
  2. electron carrier activity Source: UniProtKB
  3. phenanthrene-9,10-epoxide hydrolase activity Source: UniProtKB

GO - Biological processi

  1. carbohydrate metabolic process Source: ProtInc
  2. cellular aldehyde metabolic process Source: ProtInc
  3. daunorubicin metabolic process Source: UniProtKB
  4. doxorubicin metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NADP

Enzyme and pathway databases

SABIO-RKO43488.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:AKR7A2
Synonyms:AFAR, AFAR1, AKR7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:389. AKR7A2.

Subcellular locationi

Golgi apparatus By similarity. Cytoplasm 1 Publication

GO - Cellular componenti

  1. Golgi apparatus Source: UniProtKB-SubCell
  2. extracellular vesicular exosome Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Golgi apparatus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24682.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 359359Aflatoxin B1 aldehyde reductase member 2
PRO_0000070375Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei128 – 1281N6-acetyllysine By similarity
Modified residuei236 – 2361N6-succinyllysine By similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiO43488.
PaxDbiO43488.
PRIDEiO43488.

2D gel databases

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

PTM databases

PhosphoSiteiO43488.

Miscellaneous databases

PMAP-CutDBO43488.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

ArrayExpressiO43488.
BgeeiO43488.
CleanExiHS_AKR7A2.
GenevestigatoriO43488.

Organism-specific databases

HPAiCAB032587.
CAB032841.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi114142. 6 interactions.
IntActiO43488. 2 interactions.
MINTiMINT-5002225.
STRINGi9606.ENSP00000235835.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi39 – 435
Turni48 – 503
Helixi53 – 6513
Beta strandi70 – 723
Helixi77 – 804
Helixi81 – 877
Beta strandi101 – 1066
Helixi116 – 13015
Beta strandi135 – 1406
Helixi149 – 16113
Beta strandi164 – 1729
Helixi175 – 18814
Beta strandi193 – 1997
Helixi206 – 2083
Helixi211 – 2188
Beta strandi221 – 2255
Helixi229 – 2346
Helixi239 – 2424
Turni243 – 2453
Beta strandi252 – 2543
Helixi257 – 2648
Helixi267 – 28418
Helixi285 – 2873
Helixi291 – 30212
Helixi307 – 3093
Beta strandi312 – 3154
Helixi320 – 33011
Helixi337 – 35014
Helixi351 – 3533

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2BP1X-ray2.40A/B/C/D30-359[»]
ProteinModelPortaliO43488.
SMRiO43488. Positions 37-359.

Miscellaneous databases

EvolutionaryTraceiO43488.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0667.
HOGENOMiHOG000250286.
HOVERGENiHBG050576.
InParanoidiO43488.
KOiK15303.
OMAiCTVKIAT.
OrthoDBiEOG77127F.
PhylomeDBiO43488.
TreeFamiTF329173.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR001395. Aldo/ket_red.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR11732. PTHR11732. 1 hit.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
SUPFAMiSSF51430. SSF51430. 1 hit.

Sequencei

Sequence statusi: Complete.

O43488-1 [UniParc]FASTAAdd to Basket

« Hide

MLSAASRVVS RAAVHCALRS PPPEARALAM SRPPPPRVAS VLGTMEMGRR    50
MDAPASAAAV RAFLERGHTE LDTAFMYSDG QSETILGGLG LGLGGGDCRV 100
KIATKANPWD GKSLKPDSVR SQLETSLKRL QCPQVDLFYL HAPDHGTPVE 150
ETLHACQRLH QEGKFVELGL SNYASWEVAE ICTLCKSNGW ILPTVYQGMY 200
NATTRQVETE LFPCLRHFGL RFYAYNPLAG GLLTGKYKYE DKDGKQPVGR 250
FFGNSWAETY RNRFWKEHHF EAIALVEKAL QAAYGASAPS VTSAALRWMY 300
HHSQLQGAHG DAVILGMSSL EQLEQNLAAT EEGPLEPAVV DAFNQAWHLV 350
AHECPNYFR 359
Length:359
Mass (Da):39,589
Last modified:November 14, 2003 - v3
Checksum:i2C9775FE4B977D2A
GO

Sequence cautioni

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti135 – 1351V → M.
Corresponds to variant rs6670759 [ dbSNP | Ensembl ].
VAR_048209
Natural varianti142 – 1421A → T.2 Publications
Corresponds to variant rs1043657 [ dbSNP | Ensembl ].
VAR_017413
Natural varianti157 – 1571Q → H.1 Publication
Corresponds to variant rs859208 [ dbSNP | Ensembl ].
VAR_017414
Natural varianti180 – 1801E → K.
Corresponds to variant rs859210 [ dbSNP | Ensembl ].
VAR_060222
Natural varianti198 – 1981G → S.
Corresponds to variant rs2231200 [ dbSNP | Ensembl ].
VAR_048210
Natural varianti214 – 2141C → Y.
Corresponds to variant rs2235794 [ dbSNP | Ensembl ].
VAR_017415
Natural varianti255 – 2551S → N.
Corresponds to variant rs2231203 [ dbSNP | Ensembl ].
VAR_048211

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS194.1.
RefSeqiNP_003680.2. NM_003689.3.
UniGeneiHs.571886.

Genome annotation databases

EnsembliENST00000235835; ENSP00000235835; ENSG00000053371.
GeneIDi8574.
KEGGihsa:8574.
UCSCiuc001bbw.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS194.1.
RefSeqi NP_003680.2. NM_003689.3.
UniGenei Hs.571886.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2BP1 X-ray 2.40 A/B/C/D 30-359 [» ]
ProteinModelPortali O43488.
SMRi O43488. Positions 37-359.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114142. 6 interactions.
IntActi O43488. 2 interactions.
MINTi MINT-5002225.
STRINGi 9606.ENSP00000235835.

PTM databases

PhosphoSitei O43488.

2D gel databases

REPRODUCTION-2DPAGE IPI00305978.
O43488.
UCD-2DPAGE O43488.

Proteomic databases

MaxQBi O43488.
PaxDbi O43488.
PRIDEi O43488.

Protocols and materials databases

DNASUi 8574.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000235835 ; ENSP00000235835 ; ENSG00000053371 .
GeneIDi 8574.
KEGGi hsa:8574.
UCSCi uc001bbw.3. human.

Organism-specific databases

CTDi 8574.
GeneCardsi GC01M019630.
H-InvDB HIX0000198.
HGNCi HGNC:389. AKR7A2.
HPAi CAB032587.
CAB032841.
MIMi 603418. gene.
neXtProti NX_O43488.
PharmGKBi PA24682.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0667.
HOGENOMi HOG000250286.
HOVERGENi HBG050576.
InParanoidi O43488.
KOi K15303.
OMAi CTVKIAT.
OrthoDBi EOG77127F.
PhylomeDBi O43488.
TreeFami TF329173.

Enzyme and pathway databases

SABIO-RK O43488.

Miscellaneous databases

EvolutionaryTracei O43488.
GeneWikii AKR7A2.
GenomeRNAii 8574.
NextBioi 32161.
PMAP-CutDB O43488.
PROi O43488.
SOURCEi Search...

Gene expression databases

ArrayExpressi O43488.
Bgeei O43488.
CleanExi HS_AKR7A2.
Genevestigatori O43488.

Family and domain databases

Gene3Di 3.20.20.100. 1 hit.
InterProi IPR001395. Aldo/ket_red.
IPR023210. NADP_OxRdtase_dom.
[Graphical view ]
PANTHERi PTHR11732. PTHR11732. 1 hit.
Pfami PF00248. Aldo_ket_red. 1 hit.
[Graphical view ]
SUPFAMi SSF51430. SSF51430. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiARK72_HUMAN
AccessioniPrimary (citable) accession number: O43488
Secondary accession number(s): O75749, Q5TG63
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Caution

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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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