ID   ALD2_MOUSE              Reviewed;         316 AA.
AC   P45377; Q99JN4;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   27-MAR-2024, entry version 171.
DE   RecName: Full=Aldose reductase-related protein 2;
DE            Short=AR;
DE            EC=1.1.1.21;
DE   AltName: Full=Aldehyde reductase;
DE   AltName: Full=Fibroblast growth factor-regulated protein;
DE   AltName: Full=Protein FR-1;
GN   Name=Akr1b8; Synonyms=Fgfrp;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ;
RX   PubMed=7510692; DOI=10.1016/s0021-9258(17)37237-x;
RA   Donohue P.J., Alberts G.F., Hampton B.S., Winkles J.A.;
RT   "A delayed-early gene activated by fibroblast growth factor-1 encodes a
RT   protein related to aldose reductase.";
RL   J. Biol. Chem. 269:8604-8609(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
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   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Lung, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH NADPH AND INHIBITOR.
RX   PubMed=7578036; DOI=10.1021/bi00044a009;
RA   Wilson D.K., Nakano T., Petrash M., Quiocho F.A.;
RT   "1.7-A structure of FR-1, a fibroblast growth factor-induced member of the
RT   aldo-keto reductase family, complexed with coenzyme and inhibitor.";
RL   Biochemistry 34:14323-14330(1995).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an alditol + NAD(+) = an aldose + H(+) + NADH;
CC         Xref=Rhea:RHEA:12785, Rhea:RHEA-COMP:9554, Rhea:RHEA-COMP:9555,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15693, ChEBI:CHEBI:17522,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.21;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an alditol + NADP(+) = an aldose + H(+) + NADPH;
CC         Xref=Rhea:RHEA:12789, Rhea:RHEA-COMP:9554, Rhea:RHEA-COMP:9555,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15693, ChEBI:CHEBI:17522,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.21;
CC   -!- SUBUNIT: Monomer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- INDUCTION: By FGF-1.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR   EMBL; U04204; AAA16953.1; -; mRNA.
DR   EMBL; BC005789; AAH05789.1; -; mRNA.
DR   CCDS; CCDS19991.1; -.
DR   PIR; A53440; A53440.
DR   RefSeq; NP_032038.1; NM_008012.1.
DR   PDB; 1FRB; X-ray; 1.70 A; A=2-316.
DR   PDBsum; 1FRB; -.
DR   AlphaFoldDB; P45377; -.
DR   SMR; P45377; -.
DR   STRING; 10090.ENSMUSP00000040244; -.
DR   SwissLipids; SLP:000001939; -.
DR   GlyGen; P45377; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P45377; -.
DR   PhosphoSitePlus; P45377; -.
DR   SwissPalm; P45377; -.
DR   REPRODUCTION-2DPAGE; IPI00273096; -.
DR   REPRODUCTION-2DPAGE; P45377; -.
DR   EPD; P45377; -.
DR   jPOST; P45377; -.
DR   MaxQB; P45377; -.
DR   PaxDb; 10090-ENSMUSP00000040244; -.
DR   PeptideAtlas; P45377; -.
DR   ProteomicsDB; 296393; -.
DR   Pumba; P45377; -.
DR   DNASU; 14187; -.
DR   Ensembl; ENSMUST00000038406.7; ENSMUSP00000040244.6; ENSMUSG00000029762.7.
DR   GeneID; 14187; -.
DR   KEGG; mmu:14187; -.
DR   UCSC; uc009bgz.1; mouse.
DR   AGR; MGI:107673; -.
DR   CTD; 14187; -.
DR   MGI; MGI:107673; Akr1b8.
DR   VEuPathDB; HostDB:ENSMUSG00000029762; -.
DR   eggNOG; KOG1577; Eukaryota.
DR   GeneTree; ENSGT00940000154773; -.
DR   HOGENOM; CLU_023205_0_0_1; -.
DR   InParanoid; P45377; -.
DR   OMA; KLWPTDQ; -.
DR   OrthoDB; 890110at2759; -.
DR   PhylomeDB; P45377; -.
DR   TreeFam; TF106492; -.
DR   Reactome; R-MMU-193144; Estrogen biosynthesis.
DR   BioGRID-ORCS; 14187; 2 hits in 79 CRISPR screens.
DR   ChiTaRS; Akr1b8; mouse.
DR   EvolutionaryTrace; P45377; -.
DR   PRO; PR:P45377; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; P45377; Protein.
DR   Bgee; ENSMUSG00000029762; Expressed in pyloric antrum and 215 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005576; C:extracellular region; ISO:MGI.
DR   GO; GO:0005764; C:lysosome; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR   GO; GO:0008106; F:alcohol dehydrogenase (NADP+) activity; ISO:MGI.
DR   GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; ISO:MGI.
DR   GO; GO:0004303; F:estradiol 17-beta-dehydrogenase [NAD(P)] activity; ISO:MGI.
DR   GO; GO:0045550; F:geranylgeranyl reductase activity; ISO:MGI.
DR   GO; GO:0047718; F:indanol dehydrogenase activity; ISO:MGI.
DR   GO; GO:0070401; F:NADP+ binding; ISO:MGI.
DR   GO; GO:0052650; F:NADP-retinol dehydrogenase activity; ISO:MGI.
DR   GO; GO:0070402; F:NADPH binding; ISO:MGI.
DR   GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; ISO:MGI.
DR   GO; GO:0016918; F:retinal binding; ISO:MGI.
DR   GO; GO:0001758; F:retinal dehydrogenase activity; ISO:MGI.
DR   GO; GO:0019751; P:polyol metabolic process; IEA:Ensembl.
DR   GO; GO:0042574; P:retinal metabolic process; IEA:Ensembl.
DR   CDD; cd19107; AKR_AKR1B1-19; 1.
DR   Gene3D; 3.20.20.100; NADP-dependent oxidoreductase domain; 1.
DR   InterPro; IPR020471; AKR.
DR   InterPro; IPR018170; Aldo/ket_reductase_CS.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR   PANTHER; PTHR11732:SF278; ALDO-KETO REDUCTASE FAMILY 1 MEMBER B10; 1.
DR   PANTHER; PTHR11732; ALDO/KETO REDUCTASE; 1.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   PIRSF; PIRSF000097; AKR; 1.
DR   PRINTS; PR00069; ALDKETRDTASE.
DR   SUPFAM; SSF51430; NAD(P)-linked oxidoreductase; 1.
DR   PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR   PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR   PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
DR   Genevisible; P45377; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; NADP; Oxidoreductase; Reference proteome.
FT   CHAIN           1..316
FT                   /note="Aldose reductase-related protein 2"
FT                   /id="PRO_0000124631"
FT   ACT_SITE        49
FT                   /note="Proton donor"
FT   BINDING         111
FT                   /ligand="substrate"
FT   BINDING         211..273
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|PubMed:7578036"
FT   SITE            78
FT                   /note="Lowers pKa of active site Tyr"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        242
FT                   /note="E -> K (in Ref. 2; AAH05789)"
FT                   /evidence="ECO:0000305"
FT   STRAND          4..6
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   STRAND          12..16
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           25..37
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   STRAND          42..44
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           47..49
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           52..64
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           70..72
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   STRAND          74..79
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           81..83
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           86..100
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   STRAND          105..110
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           138..150
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   STRAND          153..161
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           164..171
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   STRAND          182..186
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           194..202
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   STRAND          206..211
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   TURN            228..230
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           232..240
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           245..254
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   TURN            255..257
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           267..274
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           283..290
FT                   /evidence="ECO:0007829|PDB:1FRB"
FT   HELIX           302..304
FT                   /evidence="ECO:0007829|PDB:1FRB"
SQ   SEQUENCE   316 AA;  36121 MW;  0C6F0A7BA806497C CRC64;
     MATFVELSTK AKMPIVGLGT WKSPPNQVKE AVKAAIDAGY RHIDCAYAYC NENEVGEAIQ
     EKIKEKAVQR EDLFIVSKLW PTCFEKKLLK EAFQKTLTDL KLDYLDLYLI HWPQGLQPGK
     ELFPKDDQGR ILTSKTTFLE AWEGMEELVD QGLVKALGVS NFNHFQIERL LNKPGLKHKP
     VTNQVECHPY LTQEKLIQYC HSKGISVTAY SPLGSPDRPS AKPEDPSLLE DPKIKEIAAK
     HEKTSAQVLI RFHIQRNVVV IPKSVTPSRI QENIQVFDFQ LSDEEMATIL SFNRNWRACL
     LPETVNMEEY PYDAEY
//