AKCL2_HUMAN
ID AKCL2_HUMAN Reviewed; 320 AA.
AC Q96JD6; Q86Z16; Q86Z17; Q86Z18; Q9BU71;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=1,5-anhydro-D-fructose reductase;
DE Short=AF reductase;
DE EC=1.1.1.263 {ECO:0000250|UniProtKB:Q9DCT1};
DE AltName: Full=Aldo-keto reductase family 1 member C-like protein 2;
DE AltName: Full=Aldo-keto reductase family 1 member E2;
DE AltName: Full=LoopADR;
DE AltName: Full=Testis aldo-keto reductase {ECO:0000303|PubMed:15118078};
DE Short=htAKR {ECO:0000303|PubMed:15118078};
DE AltName: Full=Testis-specific protein;
DE Short=hTSP;
GN Name=AKR1E2; Synonyms=AKR1CL2, AKRDC1;
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] (ISOFORMS 2; 3; 4 AND 5), BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=12604216; DOI=10.1016/s0009-2797(02)00187-4;
RA Nishinaka T., Azuma Y., Ushijima S., Miki T., Yabe-Nishimura C.;
RT "Human testis specific protein: a new member of aldo-keto reductase
RT superfamily.";
RL Chem. Biol. Interact. 143:299-305(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Small intestine;
RA Hyndman D.J., Li L., Flynn T.G.;
RT "LoopADR: a novel human aldo-keto reductase.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Lung;
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, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND
RP ALTERNATIVE SPLICING.
RX PubMed=15118078; DOI=10.1093/molehr/gah062;
RA Azuma Y., Nishinaka T., Ushijima S., Soh J., Katsuyama M., Lu H.P.,
RA Kawata M., Yabe-Nishimura C., Miki T.;
RT "Characterization of htAKR, a novel gene product in the aldo-keto reductase
RT family specifically expressed in human testis.";
RL Mol. Hum. Reprod. 10:527-533(2004).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of 1,5-anhydro-D-
CC fructose (AF) to 1,5-anhydro-D-glucitol (By similarity). Has low NADPH-
CC dependent reductase activity towards 9,10-phenanthrenequinone (in
CC vitro) (PubMed:12604216, PubMed:15118078).
CC {ECO:0000250|UniProtKB:Q9DCT1, ECO:0000269|PubMed:12604216,
CC ECO:0000269|PubMed:15118078}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,5-anhydro-D-glucitol + NADP(+) = 1,5-anhydro-D-fructose +
CC H(+) + NADPH; Xref=Rhea:RHEA:20665, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16070, ChEBI:CHEBI:16715, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.1.1.263;
CC Evidence={ECO:0000250|UniProtKB:Q9DCT1};
CC -!- ACTIVITY REGULATION: Inhibited by p-chloromercuribenzoic acid and
CC alkyliodines. {ECO:0000250|UniProtKB:P82125}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.1 uM for 9,10-phenanthrenequinone with NADPH as cofactor
CC {ECO:0000269|PubMed:12604216};
CC KM=44.3 uM for 9,10-phenanthrenequinone (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:15118078};
CC KM=166 uM for NADPH (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:15118078};
CC KM=2.3 mM for NADH (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:15118078};
CC Vmax=0.42 nmol/min/mg enzyme towards 9,10-phenanthrenequinone with
CC NADPH as cofactor {ECO:0000269|PubMed:12604216};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P82125}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q96JD6-1; Sequence=Displayed;
CC Name=2; Synonyms=HTSP2 {ECO:0000303|PubMed:12604216}, htAKR2
CC {ECO:0000303|PubMed:15118078};
CC IsoId=Q96JD6-2; Sequence=VSP_025615;
CC Name=3; Synonyms=HTSP1 {ECO:0000303|PubMed:12604216}, htAKR1
CC {ECO:0000303|PubMed:15118078};
CC IsoId=Q96JD6-3; Sequence=VSP_025615, VSP_025616, VSP_025617;
CC Name=4; Synonyms=HTSP4 {ECO:0000303|PubMed:12604216}, htAKR4
CC {ECO:0000303|PubMed:15118078};
CC IsoId=Q96JD6-4; Sequence=VSP_025616, VSP_025617;
CC Name=5; Synonyms=HTSP3 {ECO:0000303|PubMed:12604216}, htAKR3
CC {ECO:0000303|PubMed:15118078};
CC IsoId=Q96JD6-5; Sequence=VSP_025614;
CC -!- TISSUE SPECIFICITY: Specifically expressed in testis (PubMed:12604216,
CC PubMed:15118078). Expressed in testicular germ cells and testis
CC interstitial cells (PubMed:15118078). {ECO:0000269|PubMed:12604216,
CC ECO:0000269|PubMed:15118078}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; AB040820; BAC54565.1; -; mRNA.
DR EMBL; AB040821; BAC54566.1; -; mRNA.
DR EMBL; AB040822; BAC54567.1; -; mRNA.
DR EMBL; AB055603; BAC54568.1; -; mRNA.
DR EMBL; AF263242; AAK58523.1; -; mRNA.
DR EMBL; AC091817; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002862; AAH02862.1; -; mRNA.
DR CCDS; CCDS31134.1; -. [Q96JD6-1]
DR CCDS; CCDS59209.1; -. [Q96JD6-2]
DR CCDS; CCDS59210.1; -. [Q96JD6-5]
DR RefSeq; NP_001035267.1; NM_001040177.2. [Q96JD6-1]
DR RefSeq; NP_001257950.1; NM_001271021.1. [Q96JD6-2]
DR RefSeq; NP_001257954.1; NM_001271025.1. [Q96JD6-5]
DR AlphaFoldDB; Q96JD6; -.
DR SMR; Q96JD6; -.
DR STRING; 9606.ENSP00000298375; -.
DR BindingDB; Q96JD6; -.
DR DrugBank; DB06077; Lumateperone.
DR iPTMnet; Q96JD6; -.
DR PhosphoSitePlus; Q96JD6; -.
DR BioMuta; AKR1E2; -.
DR DMDM; 269849539; -.
DR EPD; Q96JD6; -.
DR jPOST; Q96JD6; -.
DR MassIVE; Q96JD6; -.
DR PaxDb; Q96JD6; -.
DR PeptideAtlas; Q96JD6; -.
DR PRIDE; Q96JD6; -.
DR ProteomicsDB; 76943; -. [Q96JD6-1]
DR ProteomicsDB; 76944; -. [Q96JD6-2]
DR ProteomicsDB; 76945; -. [Q96JD6-3]
DR ProteomicsDB; 76946; -. [Q96JD6-4]
DR Antibodypedia; 23956; 176 antibodies from 27 providers.
DR DNASU; 83592; -.
DR Ensembl; ENST00000298375.12; ENSP00000298375.7; ENSG00000165568.18. [Q96JD6-1]
DR Ensembl; ENST00000334019.4; ENSP00000335034.4; ENSG00000165568.18. [Q96JD6-2]
DR Ensembl; ENST00000345253.9; ENSP00000335603.5; ENSG00000165568.18. [Q96JD6-5]
DR Ensembl; ENST00000463345.5; ENSP00000436794.1; ENSG00000165568.18. [Q96JD6-4]
DR Ensembl; ENST00000532248.5; ENSP00000432947.1; ENSG00000165568.18. [Q96JD6-3]
DR GeneID; 83592; -.
DR KEGG; hsa:83592; -.
DR MANE-Select; ENST00000298375.12; ENSP00000298375.7; NM_001040177.3; NP_001035267.1.
DR UCSC; uc001ihi.5; human. [Q96JD6-1]
DR CTD; 83592; -.
DR DisGeNET; 83592; -.
DR GeneCards; AKR1E2; -.
DR HGNC; HGNC:23437; AKR1E2.
DR HPA; ENSG00000165568; Tissue enriched (testis).
DR MIM; 617451; gene.
DR neXtProt; NX_Q96JD6; -.
DR OpenTargets; ENSG00000165568; -.
DR PharmGKB; PA165548224; -.
DR VEuPathDB; HostDB:ENSG00000165568; -.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000153272; -.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; Q96JD6; -.
DR OMA; AEMYANE; -.
DR OrthoDB; 1016440at2759; -.
DR PhylomeDB; Q96JD6; -.
DR TreeFam; TF106492; -.
DR BioCyc; MetaCyc:HS15341-MON; -.
DR PathwayCommons; Q96JD6; -.
DR SABIO-RK; Q96JD6; -.
DR BioGRID-ORCS; 83592; 12 hits in 1076 CRISPR screens.
DR GenomeRNAi; 83592; -.
DR Pharos; Q96JD6; Tbio.
DR PRO; PR:Q96JD6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96JD6; protein.
DR Bgee; ENSG00000165568; Expressed in left testis and 146 other tissues.
DR ExpressionAtlas; Q96JD6; baseline and differential.
DR Genevisible; Q96JD6; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0050571; F:1,5-anhydro-D-fructose reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR CDD; cd19110; AKR_AKR1E1-2; 1.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
DR InterPro; IPR044484; AKR1E2.
DR InterPro; IPR018170; Aldo/ket_reductase_CS.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR PIRSF; PIRSF000097; AKR; 1.
DR PRINTS; PR00069; ALDKETRDTASE.
DR SUPFAM; SSF51430; SSF51430; 1.
DR PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..320
FT /note="1,5-anhydro-D-fructose reductase"
FT /id="PRO_0000287880"
FT ACT_SITE 40
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT BINDING 35
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT BINDING 102
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT BINDING 194
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT BINDING 265..277
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT SITE 69
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT VAR_SEQ 154..251
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:12604216"
FT /id="VSP_025614"
FT VAR_SEQ 194..250
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12604216"
FT /id="VSP_025615"
FT VAR_SEQ 307
FT /note="I -> M (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12604216,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_025616"
FT VAR_SEQ 308..320
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12604216,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_025617"
FT VARIANT 52
FT /note="C -> G (in dbSNP:rs35429729)"
FT /id="VAR_032356"
FT VARIANT 86
FT /note="K -> R (in dbSNP:rs17133693)"
FT /id="VAR_032357"
FT CONFLICT 312
FT /note="K -> N (in Ref. 2; AAK58523)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 320 AA; 36589 MW; A73E06225E7F15DD CRC64;
MGDIPAVGLS SWKASPGKVT EAVKEAIDAG YRHFDCAYFY HNEREVGAGI RCKIKEGAVR
REDLFIATKL WCTCHKKSLV ETACRKSLKA LKLNYLDLYL IHWPMGFKPP HPEWIMSCSE
LSFCLSHPRV QDLPLDESNM VIPSDTDFLD TWEAMEDLVI TGLVKNIGVS NFNHEQLERL
LNKPGLRFKP LTNQIECHPY LTQKNLISFC QSRDVSVTAY RPLGGSCEGV DLIDNPVIKR
IAKEHGKSPA QILIRFQIQR NVIVIPGSIT PSHIKENIQV FDFELTQHDM DNILSLNRNL
RLAMFPITKN HKDYPFHIEY
