ARK73_HUMAN
ID ARK73_HUMAN Reviewed; 331 AA.
AC O95154; Q86SR4; Q8IVN6; Q8N5V6; Q8TAX1; Q9NUC3;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Aflatoxin B1 aldehyde reductase member 3;
DE EC=1.-.-.-;
DE AltName: Full=AFB1 aldehyde reductase 2;
DE Short=AFB1-AR 2;
GN Name=AKR7A3; Synonyms=AFAR2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, AND VARIANTS MET-138; ASP-215
RP AND ALA-323.
RC TISSUE=Liver;
RX PubMed=10383892; DOI=10.1093/carcin/20.7.1215;
RA Knight L.P., Primiano T., Groopman J.D., Kensler T.W., Sutter T.R.;
RT "cDNA cloning, expression and activity of a second human aflatoxin B1-
RT metabolizing member of the aldo-keto reductase superfamily, AKR7A3.";
RL Carcinogenesis 20:1215-1223(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS ASP-215 AND
RP ALA-323.
RX PubMed=12879023; DOI=10.1038/sj.onc.1206684;
RA Praml C., Savelyeva L., Schwab M.;
RT "Aflatoxin B1 aldehyde reductase (AFAR) genes cluster at 1p35-1p36.1 in a
RT region frequently altered in human tumour cells.";
RL Oncogene 22:4765-4773(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS MET-138; ASP-215 AND
RP ALA-323.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18416522; DOI=10.1021/tx7004458;
RA Bodreddigari S., Jones L.K., Egner P.A., Groopman J.D., Sutter C.H.,
RA Roebuck B.D., Guengerich F.P., Kensler T.W., Sutter T.R.;
RT "Protection against aflatoxin B1-induced cytotoxicity by expression of the
RT cloned aflatoxin B1-aldehyde reductases rat AKR7A1 and human AKR7A3.";
RL Chem. Res. Toxicol. 21:1134-1142(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85 AND THR-227, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 8-331 IN COMPLEX WITH NADP, AND
RP SUBUNIT.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human aflatoxin B1 aldehyde reductase member 3.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Can reduce the dialdehyde protein-binding form of aflatoxin
CC B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in
CC protection of liver against the toxic and carcinogenic effects of AFB1,
CC a potent hepatocarcinogen. {ECO:0000269|PubMed:18416522}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|Ref.7}.
CC -!- INTERACTION:
CC O95154; O43488: AKR7A2; NbExp=6; IntAct=EBI-748869, EBI-748855;
CC O95154; O95154: AKR7A3; NbExp=6; IntAct=EBI-748869, EBI-748869;
CC O95154; Q15323: KRT31; NbExp=3; IntAct=EBI-748869, EBI-948001;
CC O95154; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-748869, EBI-11959885;
CC O95154; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-748869, EBI-750109;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in colon, kidney, liver, pancreas,
CC adenocarcinoma and endometrium. {ECO:0000269|PubMed:12879023,
CC ECO:0000269|PubMed:18416522}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto
CC reductase 2 subfamily. {ECO:0000305}.
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DR EMBL; AF040639; AAD02195.1; -; mRNA.
DR EMBL; AJ271799; CAC81076.1; -; mRNA.
DR EMBL; AL035413; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025709; AAH25709.1; -; mRNA.
DR EMBL; BC031562; AAH31562.1; -; mRNA.
DR EMBL; BC042420; AAH42420.2; -; mRNA.
DR CCDS; CCDS193.1; -.
DR RefSeq; NP_036199.2; NM_012067.2.
DR PDB; 2CLP; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K=8-331.
DR PDBsum; 2CLP; -.
DR AlphaFoldDB; O95154; -.
DR SMR; O95154; -.
DR BioGRID; 116626; 17.
DR IntAct; O95154; 12.
DR STRING; 9606.ENSP00000355377; -.
DR iPTMnet; O95154; -.
DR PhosphoSitePlus; O95154; -.
DR BioMuta; AKR7A3; -.
DR jPOST; O95154; -.
DR MassIVE; O95154; -.
DR MaxQB; O95154; -.
DR PaxDb; O95154; -.
DR PeptideAtlas; O95154; -.
DR PRIDE; O95154; -.
DR ProteomicsDB; 50669; -.
DR Antibodypedia; 29611; 166 antibodies from 28 providers.
DR DNASU; 22977; -.
DR Ensembl; ENST00000361640.5; ENSP00000355377.4; ENSG00000162482.5.
DR GeneID; 22977; -.
DR KEGG; hsa:22977; -.
DR MANE-Select; ENST00000361640.5; ENSP00000355377.4; NM_012067.3; NP_036199.2.
DR UCSC; uc001bbv.2; human.
DR CTD; 22977; -.
DR DisGeNET; 22977; -.
DR GeneCards; AKR7A3; -.
DR HGNC; HGNC:390; AKR7A3.
DR HPA; ENSG00000162482; Tissue enhanced (intestine, liver, pancreas, stomach).
DR MIM; 608477; gene.
DR neXtProt; NX_O95154; -.
DR OpenTargets; ENSG00000162482; -.
DR PharmGKB; PA24683; -.
DR VEuPathDB; HostDB:ENSG00000162482; -.
DR eggNOG; ENOG502QU2T; Eukaryota.
DR GeneTree; ENSGT00940000163704; -.
DR HOGENOM; CLU_023205_1_1_1; -.
DR InParanoid; O95154; -.
DR OMA; KRYWNDT; -.
DR OrthoDB; 1226539at2759; -.
DR PhylomeDB; O95154; -.
DR TreeFam; TF329173; -.
DR PathwayCommons; O95154; -.
DR Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
DR SABIO-RK; O95154; -.
DR SignaLink; O95154; -.
DR BioGRID-ORCS; 22977; 47 hits in 1035 CRISPR screens.
DR EvolutionaryTrace; O95154; -.
DR GenomeRNAi; 22977; -.
DR Pharos; O95154; Tbio.
DR PRO; PR:O95154; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O95154; protein.
DR Bgee; ENSG00000162482; Expressed in duodenum and 178 other tissues.
DR ExpressionAtlas; O95154; baseline and differential.
DR Genevisible; O95154; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; IBA:GO_Central.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046223; P:aflatoxin catabolic process; IEA:Ensembl.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; TAS:ProtInc.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR SUPFAM; SSF51430; SSF51430; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; NAD; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..331
FT /note="Aflatoxin B1 aldehyde reductase member 3"
FT /id="PRO_0000070378"
FT ACT_SITE 49
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 44
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.7"
FT BINDING 113
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 143..144
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.7"
FT BINDING 169
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 198..208
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.7"
FT BINDING 222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.7"
FT BINDING 232
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 290..298
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.7"
FT SITE 77
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38918"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 227
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 138
FT /note="V -> M (in dbSNP:rs2231198)"
FT /evidence="ECO:0000269|PubMed:10383892,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_017416"
FT VARIANT 215
FT /note="N -> D (in dbSNP:rs1738023)"
FT /evidence="ECO:0000269|PubMed:10383892,
FT ECO:0000269|PubMed:12879023, ECO:0000269|PubMed:15489334"
FT /id="VAR_017417"
FT VARIANT 323
FT /note="T -> A (in dbSNP:rs1738025)"
FT /evidence="ECO:0000269|PubMed:10383892,
FT ECO:0000269|PubMed:12879023, ECO:0000269|PubMed:15489334"
FT /id="VAR_017418"
FT CONFLICT 51
FT /note="E -> D (in Ref. 1; AAD02195)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="L -> P (in Ref. 4; AAH42420)"
FT /evidence="ECO:0000305"
FT STRAND 11..15
FT /evidence="ECO:0007829|PDB:2CLP"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 25..36
FT /evidence="ECO:0007829|PDB:2CLP"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:2CLP"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 53..59
FT /evidence="ECO:0007829|PDB:2CLP"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:2CLP"
FT STRAND 73..78
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 88..102
FT /evidence="ECO:0007829|PDB:2CLP"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 121..133
FT /evidence="ECO:0007829|PDB:2CLP"
FT STRAND 136..144
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 147..160
FT /evidence="ECO:0007829|PDB:2CLP"
FT STRAND 165..171
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 183..190
FT /evidence="ECO:0007829|PDB:2CLP"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 201..206
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 211..214
FT /evidence="ECO:0007829|PDB:2CLP"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:2CLP"
FT STRAND 220..226
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 229..236
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 239..256
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 263..274
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:2CLP"
FT STRAND 284..287
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 292..303
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 309..322
FT /evidence="ECO:0007829|PDB:2CLP"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:2CLP"
SQ SEQUENCE 331 AA; 37206 MW; B9C32C33C7102AB3 CRC64;
MSRQLSRARP ATVLGAMEMG RRMDAPTSAA VTRAFLERGH TEIDTAFVYS EGQSETILGG
LGLRLGGSDC RVKIDTKAIP LFGNSLKPDS LRFQLETSLK RLQCPRVDLF YLHMPDHSTP
VEETLRACHQ LHQEGKFVEL GLSNYAAWEV AEICTLCKSN GWILPTVYQG MYNAITRQVE
TELFPCLRHF GLRFYAFNPL AGGLLTGKYK YEDKNGKQPV GRFFGNTWAE MYRNRYWKEH
HFEGIALVEK ALQAAYGASA PSMTSATLRW MYHHSQLQGA HGDAVILGMS SLEQLEQNLA
AAEEGPLEPA VVDAFNQAWH LVTHECPNYF R
