ID   ALDOB_MOUSE             Reviewed;         364 AA.
AC   Q91Y97; Q8K034; Q91W73;
DT   23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   24-JAN-2024, entry version 167.
DE   RecName: Full=Fructose-bisphosphate aldolase B;
DE            EC=4.1.2.13 {ECO:0000269|PubMed:25637246};
DE   AltName: Full=Aldolase 2;
DE   AltName: Full=Liver-type aldolase;
GN   Name=Aldob {ECO:0000312|MGI:MGI:87995}; Synonyms=Aldo2;
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 [GENOMIC DNA].
RC   STRAIN=129/Sv;
RA   Funari V.A., Tolan D.R.;
RT   "Mouse aldolase B (aldo2) genomic sequence of the open reading frame
RT   including first poly A site and signals.";
RL   Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Colon, Kidney, and Liver;
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   PROTEIN SEQUENCE OF 2-12 AND 108-120, CLEAVAGE OF INITIATOR METHIONINE,
RP   ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Skeletal muscle;
RA   Kanor S., Quadroni M., Bienvenut W.V.;
RL   Submitted (MAR-2006) to UniProtKB.
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36 AND THR-39, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36; THR-39 AND SER-206, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Kidney, and Liver;
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   [6]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-13; LYS-121 AND LYS-317, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
RN   [7]
RP   DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=25637246; DOI=10.1016/j.ymgme.2015.01.001;
RA   Oppelt S.A., Sennott E.M., Tolan D.R.;
RT   "Aldolase-B knockout in mice phenocopies hereditary fructose intolerance in
RT   humans.";
RL   Mol. Genet. Metab. 114:445-450(2015).
RN   [8]
RP   FUNCTION, AND INTERACTION WITH G6PD AND TP53.
RX   PubMed=35122041; DOI=10.1038/s43018-020-0086-7;
RA   Li M., He X., Guo W., Yu H., Zhang S., Wang N., Liu G., Sa R., Shen X.,
RA   Jiang Y., Tang Y., Zhuo Y., Yin C., Tu Q., Li N., Nie X., Li Y., Hu Z.,
RA   Zhu H., Ding J., Li Z., Liu T., Zhang F., Zhou H., Li S., Yue J., Yan Z.,
RA   Cheng S., Tao Y., Yin H.;
RT   "Aldolase B suppresses hepatocellular carcinogenesis by inhibiting G6PD and
RT   pentose phosphate pathways.";
RL   Nat. Cancer 1:735-747(2020).
CC   -!- FUNCTION: Catalyzes the aldol cleavage of fructose 1,6-biphosphate to
CC       form two triosephosphates dihydroxyacetone phosphate and D-
CC       glyceraldehyde 3-phosphate in glycolysis as well as the reverse
CC       stereospecific aldol addition reaction in gluconeogenesis. In
CC       fructolysis, metabolizes fructose 1-phosphate derived from the
CC       phosphorylation of dietary fructose by fructokinase into
CC       dihydroxyacetone phosphate and D-glyceraldehyde (PubMed:25637246). Acts
CC       as an adapter independently of its enzymatic activity, exerts a tumor
CC       suppressor role by stabilizing the ternary complex with G6PD and TP53
CC       to inhibit G6PD activity and keep oxidative pentose phosphate
CC       metabolism in check (PubMed:35122041). {ECO:0000269|PubMed:25637246,
CC       ECO:0000269|PubMed:35122041}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-
CC         phosphate + dihydroxyacetone phosphate; Xref=Rhea:RHEA:14729,
CC         ChEBI:CHEBI:32966, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776; EC=4.1.2.13;
CC         Evidence={ECO:0000269|PubMed:25637246};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14730;
CC         Evidence={ECO:0000305|PubMed:25637246};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14731;
CC         Evidence={ECO:0000305|PubMed:25637246};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-fructose 1-phosphate = D-glyceraldehyde +
CC         dihydroxyacetone phosphate; Xref=Rhea:RHEA:30851, ChEBI:CHEBI:17378,
CC         ChEBI:CHEBI:57642, ChEBI:CHEBI:138881;
CC         Evidence={ECO:0000269|PubMed:25637246};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30852;
CC         Evidence={ECO:0000305|PubMed:25637246};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30853;
CC         Evidence={ECO:0000305|PubMed:25637246};
CC   -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC       phosphate and glycerone phosphate from D-glucose: step 4/4.
CC       {ECO:0000305|PubMed:25637246}.
CC   -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC       {ECO:0000305|PubMed:25637246}.
CC   -!- PATHWAY: Carbohydrate metabolism; fructose metabolism.
CC       {ECO:0000269|PubMed:25637246}.
CC   -!- SUBUNIT: Homotetramer. Interacts with BBS1, BBS2, BBS4 and BBS7. Forms
CC       a ternary complex with G6PD and TP53; this interaction is direct.
CC       {ECO:0000269|PubMed:35122041}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P05062}. Cytoplasm, cytoskeleton, microtubule
CC       organizing center, centrosome, centriolar satellite
CC       {ECO:0000250|UniProtKB:P05062}.
CC   -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate. On
CC       a fructose diet, they develop fructose intolerance associated with
CC       hepatic steatosis and mortality. {ECO:0000269|PubMed:25637246}.
CC   -!- MISCELLANEOUS: In vertebrates, 3 forms of this ubiquitous glycolytic
CC       enzyme are found, aldolase A in muscle, aldolase B in liver and
CC       aldolase C in brain.
CC   -!- SIMILARITY: Belongs to the class I fructose-bisphosphate aldolase
CC       family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF403567; AAL06323.1; -; Genomic_DNA.
DR   EMBL; AF403565; AAL06323.1; JOINED; Genomic_DNA.
DR   EMBL; AF403566; AAL06323.1; JOINED; Genomic_DNA.
DR   EMBL; BC016435; AAH16435.1; -; mRNA.
DR   EMBL; BC022113; AAH22113.1; -; mRNA.
DR   EMBL; BC024056; AAH24056.1; -; mRNA.
DR   EMBL; BC024112; AAH24112.1; -; mRNA.
DR   EMBL; BC026577; AAH26577.1; -; mRNA.
DR   EMBL; BC030724; AAH30724.1; -; mRNA.
DR   EMBL; BC030725; AAH30725.1; -; mRNA.
DR   EMBL; BC034169; AAH34169.1; -; mRNA.
DR   EMBL; BC034171; AAH34171.1; -; mRNA.
DR   EMBL; BC034172; AAH34172.1; -; mRNA.
DR   EMBL; BC034173; AAH34173.1; -; mRNA.
DR   EMBL; BC036130; AAH36130.1; -; mRNA.
DR   EMBL; BC036131; AAH36131.1; -; mRNA.
DR   EMBL; BC036132; AAH36132.1; -; mRNA.
DR   EMBL; BC036133; AAH36133.1; -; mRNA.
DR   CCDS; CCDS18176.1; -.
DR   RefSeq; NP_659152.1; NM_144903.3.
DR   AlphaFoldDB; Q91Y97; -.
DR   SMR; Q91Y97; -.
DR   BioGRID; 230944; 1.
DR   STRING; 10090.ENSMUSP00000029987; -.
DR   CarbonylDB; Q91Y97; -.
DR   iPTMnet; Q91Y97; -.
DR   MetOSite; Q91Y97; -.
DR   PhosphoSitePlus; Q91Y97; -.
DR   SwissPalm; Q91Y97; -.
DR   CPTAC; non-CPTAC-3333; -.
DR   CPTAC; non-CPTAC-3334; -.
DR   jPOST; Q91Y97; -.
DR   MaxQB; Q91Y97; -.
DR   PaxDb; 10090-ENSMUSP00000029987; -.
DR   PeptideAtlas; Q91Y97; -.
DR   ProteomicsDB; 285809; -.
DR   Pumba; Q91Y97; -.
DR   Antibodypedia; 1025; 473 antibodies from 33 providers.
DR   DNASU; 230163; -.
DR   Ensembl; ENSMUST00000029987.10; ENSMUSP00000029987.10; ENSMUSG00000028307.10.
DR   GeneID; 230163; -.
DR   KEGG; mmu:230163; -.
DR   UCSC; uc008svw.1; mouse.
DR   AGR; MGI:87995; -.
DR   CTD; 229; -.
DR   MGI; MGI:87995; Aldob.
DR   VEuPathDB; HostDB:ENSMUSG00000028307; -.
DR   eggNOG; KOG1557; Eukaryota.
DR   GeneTree; ENSGT00950000182987; -.
DR   HOGENOM; CLU_031243_0_0_1; -.
DR   InParanoid; Q91Y97; -.
DR   OMA; ANCQAAQ; -.
DR   OrthoDB; 3664741at2759; -.
DR   PhylomeDB; Q91Y97; -.
DR   TreeFam; TF314203; -.
DR   Reactome; R-MMU-70171; Glycolysis.
DR   Reactome; R-MMU-70263; Gluconeogenesis.
DR   Reactome; R-MMU-70350; Fructose catabolism.
DR   UniPathway; UPA00109; UER00183.
DR   UniPathway; UPA00138; -.
DR   UniPathway; UPA00202; -.
DR   BioGRID-ORCS; 230163; 2 hits in 76 CRISPR screens.
DR   ChiTaRS; Aldob; mouse.
DR   PRO; PR:Q91Y97; -.
DR   Proteomes; UP000000589; Chromosome 4.
DR   RNAct; Q91Y97; Protein.
DR   Bgee; ENSMUSG00000028307; Expressed in right kidney and 111 other cell types or tissues.
DR   ExpressionAtlas; Q91Y97; baseline and differential.
DR   GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:MGI.
DR   GO; GO:0005815; C:microtubule organizing center; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0030867; C:rough endoplasmic reticulum membrane; ISO:MGI.
DR   GO; GO:0030868; C:smooth endoplasmic reticulum membrane; ISO:MGI.
DR   GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR   GO; GO:0008092; F:cytoskeletal protein binding; ISO:MGI.
DR   GO; GO:0070061; F:fructose binding; ISO:MGI.
DR   GO; GO:0061609; F:fructose-1-phosphate aldolase activity; IMP:MGI.
DR   GO; GO:0004332; F:fructose-bisphosphate aldolase activity; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0060090; F:molecular adaptor activity; ISO:MGI.
DR   GO; GO:0031210; F:phosphatidylcholine binding; ISO:MGI.
DR   GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; ISO:MGI.
DR   GO; GO:0006001; P:fructose catabolic process; IDA:MGI.
DR   GO; GO:0061624; P:fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate; IMP:MGI.
DR   GO; GO:0006000; P:fructose metabolic process; ISO:MGI.
DR   GO; GO:0006094; P:gluconeogenesis; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006096; P:glycolytic process; ISS:UniProtKB.
DR   GO; GO:0061625; P:glycolytic process through fructose-1-phosphate; IC:MGI.
DR   GO; GO:0061615; P:glycolytic process through fructose-6-phosphate; IC:MGI.
DR   GO; GO:0006116; P:NADH oxidation; ISO:MGI.
DR   GO; GO:1905856; P:negative regulation of pentose-phosphate shunt; ISO:MGI.
DR   GO; GO:0043434; P:response to peptide hormone; ISO:MGI.
DR   GO; GO:0010043; P:response to zinc ion; ISO:MGI.
DR   GO; GO:0070072; P:vacuolar proton-transporting V-type ATPase complex assembly; ISO:MGI.
DR   CDD; cd00948; FBP_aldolase_I_a; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 1.
DR   InterPro; IPR029768; Aldolase_I_AS.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR000741; FBA_I.
DR   NCBIfam; NF033379; FrucBisAld_I; 1.
DR   PANTHER; PTHR11627; FRUCTOSE-BISPHOSPHATE ALDOLASE; 1.
DR   PANTHER; PTHR11627:SF2; FRUCTOSE-BISPHOSPHATE ALDOLASE B; 1.
DR   Pfam; PF00274; Glycolytic; 1.
DR   SUPFAM; SSF51569; Aldolase; 1.
DR   PROSITE; PS00158; ALDOLASE_CLASS_I; 1.
DR   Genevisible; Q91Y97; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW   Glycolysis; Lyase; Phosphoprotein; Reference proteome; Schiff base.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|Ref.3"
FT   CHAIN           2..364
FT                   /note="Fructose-bisphosphate aldolase B"
FT                   /id="PRO_0000216941"
FT   ACT_SITE        188
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P00883"
FT   ACT_SITE        230
FT                   /note="Schiff-base intermediate with dihydroxyacetone-P"
FT                   /evidence="ECO:0000250|UniProtKB:P00883"
FT   BINDING         43
FT                   /ligand="beta-D-fructose 1,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:32966"
FT                   /evidence="ECO:0000250|UniProtKB:P00883"
FT   BINDING         272..274
FT                   /ligand="beta-D-fructose 1,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:32966"
FT                   /evidence="ECO:0000250|UniProtKB:P00883"
FT   BINDING         304
FT                   /ligand="beta-D-fructose 1,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:32966"
FT                   /evidence="ECO:0000250|UniProtKB:P00883"
FT   SITE            364
FT                   /note="Necessary for preference for fructose 1,6-
FT                   bisphosphate over fructose 1-phosphate"
FT                   /evidence="ECO:0000250|UniProtKB:P00883"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000269|Ref.3"
FT   MOD_RES         13
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         36
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         39
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         89
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P05062"
FT   MOD_RES         119
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P05062"
FT   MOD_RES         121
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         132
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P05062"
FT   MOD_RES         206
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         272
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P05062"
FT   MOD_RES         276
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P05062"
FT   MOD_RES         299
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00884"
FT   MOD_RES         301
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00884"
FT   MOD_RES         309
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P05062"
FT   MOD_RES         317
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   CONFLICT        81
FT                   /note="H -> Y (in Ref. 2; AAH34173)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        155..156
FT                   /note="AD -> DH (in Ref. 1; AAL06323)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   364 AA;  39507 MW;  E6CD995D0073ED47 CRC64;
     MAHRFPALTP EQKKELSEIA QRIVANGKGI LAADESVGTM GNRLQRIKVE NTEENRRQFR
     ELLFSVDNSI SQSIGGVILF HETLYQKDSQ GNLFRNVLKE KGIVVGIKLD QGGAPLAGTN
     KETTIQGLDG LSERCAQYKK DGVDFGKWRA VLRIADQCPS SLAIQENANA LARYASICQQ
     NGLVPIVEPE VLPDGDHDLE HCQYVSEKVL AAVYKALNDH HVYLEGTLLK PNMVTAGHAC
     TKKYTPEQVA MATVTALHRT VPAAVPGICF LSGGMSEEDA TLNLNAINRC PLPRPWKLSF
     SYGRALQASA LAAWGGKAAN KKATQEAFMK RAMANCQAAQ GQYVHTGSSG AAATQSLFTA
     SYTY
//