ARK74_HUMAN
ID ARK74_HUMAN Reviewed; 331 AA.
AC Q8NHP1; Q5U614;
DT 15-DEC-2003, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 7.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Aflatoxin B1 aldehyde reductase member 4;
DE EC=1.-.-.-;
DE AltName: Full=AFB1 aldehyde reductase 3;
DE Short=AFB1-AR 3;
DE AltName: Full=Aldoketoreductase 7-like;
GN Name=AKR7L; Synonyms=AFAR3, AKR7A4;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 45-331 (ISOFORM 2).
RC TISSUE=Colon;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 73-331, VARIANT THR-255, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Uterus;
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).
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 (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NHP1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NHP1-3; Sequence=VSP_059796;
CC -!- TISSUE SPECIFICITY: Mainly expressed in uterus.
CC {ECO:0000269|PubMed:12879023}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto
CC reductase 2 subfamily. {ECO:0000305}.
CC -!- CAUTION: AKR7L is both a gene and a pseudogene in the human population,
CC the reference genome corresponding currently to the non-functional
CC allele with a stop codon at position 106 (GRCh38/hg38). The sequence
CC shown here with a Arg at position 106 is the one of the functional
CC protein. The functional allele is rare. {ECO:0000305}.
CC -!- CAUTION: It has been speculated that AKR7L encodes a selenoprotein,
CC which includes a selenocysteine (Sec) residue in lieu of a UGA
CC translational termination codon at position 106 (PubMed:12879023).
CC However, there is no evidence that such a protein is produced in vivo.
CC {ECO:0000269|PubMed:12879023, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH35351.1; Type=Erroneous translation; Note==Erroneous CDS prediction.; Evidence={ECO:0000305};
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DR EMBL; AL035413; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035351; AAH35351.1; ALT_SEQ; mRNA.
DR EMBL; AJ278012; CAC79668.1; -; mRNA.
DR CCDS; CCDS192.2; -. [Q8NHP1-1]
DR RefSeq; NP_001335350.1; NM_001348421.1. [Q8NHP1-1]
DR AlphaFoldDB; Q8NHP1; -.
DR SMR; Q8NHP1; -.
DR IntAct; Q8NHP1; 1.
DR iPTMnet; Q8NHP1; -.
DR PhosphoSitePlus; Q8NHP1; -.
DR BioMuta; AKR7L; -.
DR DMDM; 294862545; -.
DR jPOST; Q8NHP1; -.
DR MassIVE; Q8NHP1; -.
DR MaxQB; Q8NHP1; -.
DR PeptideAtlas; Q8NHP1; -.
DR PRIDE; Q8NHP1; -.
DR ProteomicsDB; 73727; -. [Q8NHP1-1]
DR DNASU; 246181; -.
DR GeneID; 246181; -.
DR KEGG; hsa:246181; -.
DR UCSC; uc057cwj.1; human. [Q8NHP1-1]
DR CTD; 246181; -.
DR DisGeNET; 246181; -.
DR GeneCards; AKR7L; -.
DR HGNC; HGNC:24056; AKR7L.
DR MIM; 608478; gene.
DR neXtProt; NX_Q8NHP1; -.
DR PharmGKB; PA164715300; -.
DR InParanoid; Q8NHP1; -.
DR OrthoDB; 1226539at2759; -.
DR PhylomeDB; Q8NHP1; -.
DR PathwayCommons; Q8NHP1; -.
DR Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
DR SignaLink; Q8NHP1; -.
DR BioGRID-ORCS; 246181; 0 hits in 36 CRISPR screens.
DR ChiTaRS; AKR7L; human.
DR GenomeRNAi; 246181; -.
DR Pharos; Q8NHP1; Tdark.
DR PRO; PR:Q8NHP1; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q8NHP1; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Alternative splicing; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..331
FT /note="Aflatoxin B1 aldehyde reductase member 4"
FT /id="PRO_0000070379"
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:0000250"
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:0000250"
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:0000250"
FT BINDING 222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 232
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 290..298
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT SITE 77
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95154"
FT VAR_SEQ 170..331
FT /note="GMYSATTRQVETELFPCLRHFGLRFYAYNPLAGGLLTGKYKYEDKDGKQPVG
FT RFFGTQWAEIYRNHFWKEHHFEGIALVEKALQAAYGASAPSMTSAALRWMYHHSQLQGA
FT HGDAVILGMSSLEQLEQNLAAAEEGPLEPAVVDAFNQAWHLFAHECPNYFI -> LLEG
FT APLRGHCPGGEGPAGRVWRQRSQHDLGRPPVDVPPLTAAGCPRGRGHPGHVQPGAAGAE
FT LGSGRGRAPGAGCRGRL (in isoform 2)"
FT /id="VSP_059796"
FT VARIANT 255
FT /note="A -> T (in dbSNP:rs2235795)"
FT /evidence="ECO:0000269|PubMed:12879023"
FT /id="VAR_046190"
FT VARIANT 322
FT /note="F -> V (in dbSNP:rs2982534)"
FT /id="VAR_046191"
FT CONFLICT 186
FT /note="C -> Y (in Ref. 3; CAC79668)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 331 AA; 36970 MW; 409E866FA1D2DA56 CRC64;
MSRQLSRARP ATVLGAMEMG RRMDAPTSAA VTRAFLERGH TEIDTAFLYS DGQSETILGG
LGLRMGSSDC RVKIATKANP WIGNSLKPDS VRSQLETSLK RLQCPRVDLF YLHAPDHSAP
VEETLRACHQ LHQEGKFVEL GLSNYAAWEV AEICTLCKSN GWILPTVYQG MYSATTRQVE
TELFPCLRHF GLRFYAYNPL AGGLLTGKYK YEDKDGKQPV GRFFGTQWAE IYRNHFWKEH
HFEGIALVEK ALQAAYGASA PSMTSAALRW MYHHSQLQGA HGDAVILGMS SLEQLEQNLA
AAEEGPLEPA VVDAFNQAWH LFAHECPNYF I
