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Protein

Aflatoxin B1 aldehyde reductase member 3

Gene

AKR7A3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei44 – 441NADP1 Publication
Active sitei49 – 491Proton donorBy similarity
Sitei77 – 771Lowers pKa of active site TyrBy similarity
Binding sitei113 – 1131SubstrateBy similarity
Binding sitei169 – 1691NADPBy similarity
Binding sitei222 – 2221NADP1 Publication
Binding sitei232 – 2321SubstrateBy similarity
Binding sitei235 – 2351SubstrateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi143 – 1442NADP1 Publication
Nucleotide bindingi198 – 20811NADP1 PublicationAdd
BLAST
Nucleotide bindingi290 – 2989NADP1 Publication

GO - Molecular functioni

  • aldo-keto reductase (NADP) activity Source: Reactome
  • electron carrier activity Source: UniProtKB

GO - Biological processi

  • cellular aldehyde metabolic process Source: ProtInc
  • xenobiotic metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NAD, NADP

Enzyme and pathway databases

ReactomeiR-HSA-5423646. Aflatoxin activation and detoxification.
SABIO-RKO95154.

Names & Taxonomyi

Protein namesi
Recommended name:
Aflatoxin B1 aldehyde reductase member 3 (EC:1.-.-.-)
Alternative name(s):
AFB1 aldehyde reductase 2
Short name:
AFB1-AR 2
Gene namesi
Name:AKR7A3
Synonyms:AFAR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:390. AKR7A3.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24683.

Polymorphism and mutation databases

BioMutaiAKR7A3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 331331Aflatoxin B1 aldehyde reductase member 3PRO_0000070378Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei6 – 61PhosphoserineBy similarity
Modified residuei85 – 851PhosphoserineCombined sources
Modified residuei227 – 2271PhosphothreonineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO95154.
MaxQBiO95154.
PaxDbiO95154.
PeptideAtlasiO95154.
PRIDEiO95154.

PTM databases

iPTMnetiO95154.
PhosphoSiteiO95154.

Expressioni

Tissue specificityi

Expressed in colon, kidney, liver, pancreas, adenocarcinoma and endometrium.2 Publications

Gene expression databases

BgeeiO95154.
CleanExiHS_AKR7A3.
GenevisibleiO95154. HS.

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF2IPQ9NYB02EBI-748869,EBI-750109

Protein-protein interaction databases

BioGridi116626. 10 interactions.
IntActiO95154. 5 interactions.
MINTiMINT-1435043.
STRINGi9606.ENSP00000355377.

Structurei

Secondary structure

1
331
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi11 – 155Combined sources
Turni20 – 223Combined sources
Helixi25 – 3612Combined sources
Turni37 – 393Combined sources
Beta strandi42 – 443Combined sources
Helixi49 – 524Combined sources
Helixi53 – 597Combined sources
Beta strandi67 – 693Combined sources
Beta strandi73 – 786Combined sources
Helixi88 – 10215Combined sources
Beta strandi107 – 1126Combined sources
Helixi121 – 13313Combined sources
Beta strandi136 – 1449Combined sources
Helixi147 – 16014Combined sources
Beta strandi165 – 1717Combined sources
Helixi178 – 1803Combined sources
Helixi183 – 1908Combined sources
Beta strandi193 – 1975Combined sources
Helixi201 – 2066Combined sources
Helixi211 – 2144Combined sources
Turni215 – 2173Combined sources
Beta strandi220 – 2267Combined sources
Helixi229 – 2368Combined sources
Helixi239 – 25618Combined sources
Helixi257 – 2593Combined sources
Helixi263 – 27412Combined sources
Helixi279 – 2813Combined sources
Beta strandi284 – 2874Combined sources
Helixi292 – 30312Combined sources
Helixi309 – 32214Combined sources
Helixi323 – 3253Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CLPX-ray3.00A/B/C/D/E/F/G/H/I/J/K8-331[»]
ProteinModelPortaliO95154.
SMRiO95154. Positions 9-331.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95154.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410IDYD. Eukaryota.
COG0667. LUCA.
GeneTreeiENSGT00550000074567.
HOGENOMiHOG000250286.
HOVERGENiHBG050576.
InParanoidiO95154.
KOiK15303.
OMAiAFVYSEG.
OrthoDBiEOG77127F.
PhylomeDBiO95154.
TreeFamiTF329173.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR001395. Aldo/ket_red/Kv-b.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR11732. PTHR11732. 2 hits.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
SUPFAMiSSF51430. SSF51430. 1 hit.

Sequencei

Sequence statusi: Complete.

O95154-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRQLSRARP ATVLGAMEMG RRMDAPTSAA VTRAFLERGH TEIDTAFVYS
60 70 80 90 100
EGQSETILGG LGLRLGGSDC RVKIDTKAIP LFGNSLKPDS LRFQLETSLK
110 120 130 140 150
RLQCPRVDLF YLHMPDHSTP VEETLRACHQ LHQEGKFVEL GLSNYAAWEV
160 170 180 190 200
AEICTLCKSN GWILPTVYQG MYNAITRQVE TELFPCLRHF GLRFYAFNPL
210 220 230 240 250
AGGLLTGKYK YEDKNGKQPV GRFFGNTWAE MYRNRYWKEH HFEGIALVEK
260 270 280 290 300
ALQAAYGASA PSMTSATLRW MYHHSQLQGA HGDAVILGMS SLEQLEQNLA
310 320 330
AAEEGPLEPA VVDAFNQAWH LVTHECPNYF R
Length:331
Mass (Da):37,206
Last modified:February 21, 2001 - v2
Checksum:iB9C32C33C7102AB3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti51 – 511E → D in AAD02195 (PubMed:10383892).Curated
Sequence conflicti247 – 2471L → P in AAH42420 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti138 – 1381V → M.2 Publications
Corresponds to variant rs2231198 [ dbSNP | Ensembl ].
VAR_017416
Natural varianti215 – 2151N → D.3 Publications
Corresponds to variant rs1738023 [ dbSNP | Ensembl ].
VAR_017417
Natural varianti323 – 3231T → A.3 Publications
Corresponds to variant rs1738025 [ dbSNP | Ensembl ].
VAR_017418

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF040639 mRNA. Translation: AAD02195.1.
AJ271799 mRNA. Translation: CAC81076.1.
AL035413 Genomic DNA. Translation: CAI22232.1.
BC025709 mRNA. Translation: AAH25709.1.
BC031562 mRNA. Translation: AAH31562.1.
BC042420 mRNA. Translation: AAH42420.2.
CCDSiCCDS193.1.
RefSeqiNP_036199.2. NM_012067.2.
UniGeneiHs.6980.

Genome annotation databases

EnsembliENST00000361640; ENSP00000355377; ENSG00000162482.
GeneIDi22977.
KEGGihsa:22977.
UCSCiuc001bbv.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF040639 mRNA. Translation: AAD02195.1.
AJ271799 mRNA. Translation: CAC81076.1.
AL035413 Genomic DNA. Translation: CAI22232.1.
BC025709 mRNA. Translation: AAH25709.1.
BC031562 mRNA. Translation: AAH31562.1.
BC042420 mRNA. Translation: AAH42420.2.
CCDSiCCDS193.1.
RefSeqiNP_036199.2. NM_012067.2.
UniGeneiHs.6980.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CLPX-ray3.00A/B/C/D/E/F/G/H/I/J/K8-331[»]
ProteinModelPortaliO95154.
SMRiO95154. Positions 9-331.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116626. 10 interactions.
IntActiO95154. 5 interactions.
MINTiMINT-1435043.
STRINGi9606.ENSP00000355377.

PTM databases

iPTMnetiO95154.
PhosphoSiteiO95154.

Polymorphism and mutation databases

BioMutaiAKR7A3.

Proteomic databases

EPDiO95154.
MaxQBiO95154.
PaxDbiO95154.
PeptideAtlasiO95154.
PRIDEiO95154.

Protocols and materials databases

DNASUi22977.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361640; ENSP00000355377; ENSG00000162482.
GeneIDi22977.
KEGGihsa:22977.
UCSCiuc001bbv.2. human.

Organism-specific databases

CTDi22977.
GeneCardsiAKR7A3.
H-InvDBHIX0000196.
HGNCiHGNC:390. AKR7A3.
MIMi608477. gene.
neXtProtiNX_O95154.
PharmGKBiPA24683.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IDYD. Eukaryota.
COG0667. LUCA.
GeneTreeiENSGT00550000074567.
HOGENOMiHOG000250286.
HOVERGENiHBG050576.
InParanoidiO95154.
KOiK15303.
OMAiAFVYSEG.
OrthoDBiEOG77127F.
PhylomeDBiO95154.
TreeFamiTF329173.

Enzyme and pathway databases

ReactomeiR-HSA-5423646. Aflatoxin activation and detoxification.
SABIO-RKO95154.

Miscellaneous databases

EvolutionaryTraceiO95154.
GenomeRNAii22977.
PROiO95154.
SOURCEiSearch...

Gene expression databases

BgeeiO95154.
CleanExiHS_AKR7A3.
GenevisibleiO95154. HS.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR001395. Aldo/ket_red/Kv-b.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR11732. PTHR11732. 2 hits.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
SUPFAMiSSF51430. SSF51430. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "cDNA cloning, expression and activity of a second human aflatoxin B1-metabolizing member of the aldo-keto reductase superfamily, AKR7A3."
    Knight L.P., Primiano T., Groopman J.D., Kensler T.W., Sutter T.R.
    Carcinogenesis 20:1215-1223(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, VARIANTS MET-138; ASP-215 AND ALA-323.
    Tissue: Liver.
  2. "Aflatoxin B1 aldehyde reductase (AFAR) genes cluster at 1p35-1p36.1 in a region frequently altered in human tumour cells."
    Praml C., Savelyeva L., Schwab M.
    Oncogene 22:4765-4773(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS ASP-215 AND ALA-323.
  3. "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].
  4. "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], VARIANTS MET-138; ASP-215 AND ALA-323.
  5. "Protection against aflatoxin B1-induced cytotoxicity by expression of the cloned aflatoxin B1-aldehyde reductases rat AKR7A1 and human AKR7A3."
    Bodreddigari S., Jones L.K., Egner P.A., Groopman J.D., Sutter C.H., Roebuck B.D., Guengerich F.P., Kensler T.W., Sutter T.R.
    Chem. Res. Toxicol. 21:1134-1142(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85 AND THR-227, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  7. "Crystal structure of human aflatoxin B1 aldehyde reductase member 3."
    Structural genomics consortium (SGC)
    Submitted (FEB-2009) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 8-331 IN COMPLEX WITH NADP, SUBUNIT.

Entry informationi

Entry nameiARK73_HUMAN
AccessioniPrimary (citable) accession number: O95154
Secondary accession number(s): Q86SR4
, Q8IVN6, Q8N5V6, Q8TAX1, Q9NUC3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: July 6, 2016
This is version 140 of the entry and version 2 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

Keywords - Technical termi

3D-structure, Complete proteome, 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.