ID   HAOX1_MOUSE             Reviewed;         370 AA.
AC   Q9WU19;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 163.
DE   RecName: Full=2-Hydroxyacid oxidase 1 {ECO:0000305|PubMed:9891009};
DE            Short=HAOX1;
DE            EC=1.1.3.15 {ECO:0000305|PubMed:9891009};
DE   AltName: Full=Glycolate oxidase {ECO:0000303|PubMed:9891009};
DE            Short=GOX {ECO:0000303|PubMed:9891009};
DE   AltName: Full=Glyoxylate oxidase {ECO:0000250|UniProtKB:Q9UJM8};
DE            EC=1.2.3.5 {ECO:0000250|UniProtKB:Q9UJM8};
GN   Name=Hao1 {ECO:0000312|MGI:MGI:96011};
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], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP   TISSUE SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=9891009; DOI=10.1074/jbc.274.4.2401;
RA   Kohler S.A., Menotti E., Kuhn L.C.;
RT   "Molecular cloning of mouse glycolate oxidase. High evolutionary
RT   conservation and presence of an iron-responsive element-like sequence in
RT   the mRNA.";
RL   J. Biol. Chem. 274:2401-2407(1999).
RN   [2]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194, AND IDENTIFICATION BY
RP   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   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=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   [4]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-184, AND IDENTIFICATION BY MASS
RP   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).
CC   -!- FUNCTION: Broad substrate specificity (S)-2-hydroxy-acid oxidase that
CC       preferentially oxidizes glycolate (PubMed:9891009). The glyoxylate
CC       produced by the oxidation of glycolate can then be utilized by alanine-
CC       glyoxylate aminotransferase for the peroxisomal synthesis of glycine;
CC       this pathway appears to be an important step for the detoxification of
CC       glyoxylate which, if allowed to accumulate, may be metabolized to
CC       oxalate with formation of kidney stones (By similarity). Can also
CC       catalyze the oxidation glyoxylate, and long chain hydroxyacids such as
CC       2-hydroxyhexadecanoate and 2-hydroxyoctanoate (By similarity). Active
CC       in vitro with the artificial electron acceptor 2,6-
CC       dichlorophenolindophenol (DCIP), but O2 is believed to be the
CC       physiological electron acceptor, leading to the production of H2O2
CC       (PubMed:9891009). {ECO:0000250|UniProtKB:Q9UJM8,
CC       ECO:0000269|PubMed:9891009}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a (2S)-2-hydroxycarboxylate + O2 = a 2-oxocarboxylate + H2O2;
CC         Xref=Rhea:RHEA:16789, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC         ChEBI:CHEBI:35179, ChEBI:CHEBI:58123; EC=1.1.3.15;
CC         Evidence={ECO:0000305|PubMed:9891009};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16790;
CC         Evidence={ECO:0000305|PubMed:9891009};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glycolate + O2 = glyoxylate + H2O2; Xref=Rhea:RHEA:25311,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:29805,
CC         ChEBI:CHEBI:36655; EC=1.1.3.15;
CC         Evidence={ECO:0000305|PubMed:9891009};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25312;
CC         Evidence={ECO:0000305|PubMed:9891009};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glyoxylate + H2O + O2 = H(+) + H2O2 + oxalate;
CC         Xref=Rhea:RHEA:14837, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:30623,
CC         ChEBI:CHEBI:36655; EC=1.2.3.5;
CC         Evidence={ECO:0000250|UniProtKB:Q9UJM8};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14838;
CC         Evidence={ECO:0000250|UniProtKB:Q9UJM8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-hydroxyhexadecanoate + O2 = 2-oxohexadecanoate + H2O2;
CC         Xref=Rhea:RHEA:67944, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC         ChEBI:CHEBI:65097, ChEBI:CHEBI:176593;
CC         Evidence={ECO:0000250|UniProtKB:Q9UJM8};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67945;
CC         Evidence={ECO:0000250|UniProtKB:Q9UJM8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-hydroxyoctanoate + O2 = 2-oxooctanoate + H2O2;
CC         Xref=Rhea:RHEA:67940, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC         ChEBI:CHEBI:133514, ChEBI:CHEBI:176689;
CC         Evidence={ECO:0000250|UniProtKB:Q9UJM8};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67941;
CC         Evidence={ECO:0000250|UniProtKB:Q9UJM8};
CC   -!- COFACTOR:
CC       Name=FMN; Xref=ChEBI:CHEBI:58210;
CC         Evidence={ECO:0000250|UniProtKB:Q9UJM8};
CC   -!- PATHWAY: Amino-acid biosynthesis; glycine biosynthesis.
CC       {ECO:0000250|UniProtKB:Q9UJM8}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q9UJM8}.
CC   -!- SUBCELLULAR LOCATION: Peroxisome matrix {ECO:0000250|UniProtKB:Q9UJM8}.
CC   -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:9891009}.
CC   -!- SIMILARITY: Belongs to the FMN-dependent alpha-hydroxy acid
CC       dehydrogenase family. {ECO:0000255|PROSITE-ProRule:PRU00683}.
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DR   EMBL; AF104312; AAD25332.1; -; mRNA.
DR   CCDS; CCDS16783.1; -.
DR   RefSeq; NP_034533.1; NM_010403.2.
DR   AlphaFoldDB; Q9WU19; -.
DR   SMR; Q9WU19; -.
DR   BioGRID; 200206; 2.
DR   STRING; 10090.ENSMUSP00000028704; -.
DR   BindingDB; Q9WU19; -.
DR   ChEMBL; CHEMBL4295985; -.
DR   iPTMnet; Q9WU19; -.
DR   PhosphoSitePlus; Q9WU19; -.
DR   SwissPalm; Q9WU19; -.
DR   jPOST; Q9WU19; -.
DR   MaxQB; Q9WU19; -.
DR   PaxDb; 10090-ENSMUSP00000028704; -.
DR   ProteomicsDB; 269712; -.
DR   Antibodypedia; 8448; 480 antibodies from 32 providers.
DR   DNASU; 15112; -.
DR   Ensembl; ENSMUST00000028704.3; ENSMUSP00000028704.3; ENSMUSG00000027261.3.
DR   GeneID; 15112; -.
DR   KEGG; mmu:15112; -.
DR   UCSC; uc008mns.1; mouse.
DR   AGR; MGI:96011; -.
DR   CTD; 54363; -.
DR   MGI; MGI:96011; Hao1.
DR   VEuPathDB; HostDB:ENSMUSG00000027261; -.
DR   eggNOG; KOG0538; Eukaryota.
DR   GeneTree; ENSGT00390000018717; -.
DR   HOGENOM; CLU_020639_6_1_1; -.
DR   InParanoid; Q9WU19; -.
DR   OMA; RIWFRPK; -.
DR   OrthoDB; 276514at2759; -.
DR   PhylomeDB; Q9WU19; -.
DR   TreeFam; TF313363; -.
DR   BRENDA; 1.1.3.15; 3474.
DR   Reactome; R-MMU-389661; Glyoxylate metabolism and glycine degradation.
DR   Reactome; R-MMU-9033241; Peroxisomal protein import.
DR   UniPathway; UPA00288; -.
DR   BioGRID-ORCS; 15112; 2 hits in 78 CRISPR screens.
DR   ChiTaRS; Hao1; mouse.
DR   PRO; PR:Q9WU19; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q9WU19; Protein.
DR   Bgee; ENSMUSG00000027261; Expressed in left lobe of liver and 16 other cell types or tissues.
DR   ExpressionAtlas; Q9WU19; baseline and differential.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005782; C:peroxisomal matrix; ISO:MGI.
DR   GO; GO:0005777; C:peroxisome; IDA:HGNC-UCL.
DR   GO; GO:0003973; F:(S)-2-hydroxy-acid oxidase activity; IDA:MGI.
DR   GO; GO:0010181; F:FMN binding; ISS:UniProtKB.
DR   GO; GO:0047969; F:glyoxylate oxidase activity; ISO:MGI.
DR   GO; GO:0001561; P:fatty acid alpha-oxidation; ISS:UniProtKB.
DR   GO; GO:0006545; P:glycine biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0046296; P:glycolate catabolic process; ISS:UniProtKB.
DR   GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR   CDD; cd02809; alpha_hydroxyacid_oxid_FMN; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR012133; Alpha-hydoxy_acid_DH_FMN.
DR   InterPro; IPR000262; FMN-dep_DH.
DR   InterPro; IPR037396; FMN_HAD.
DR   InterPro; IPR008259; FMN_hydac_DH_AS.
DR   PANTHER; PTHR10578:SF137; 2-HYDROXYACID OXIDASE 1; 1.
DR   PANTHER; PTHR10578; S -2-HYDROXY-ACID OXIDASE-RELATED; 1.
DR   Pfam; PF01070; FMN_dh; 1.
DR   PIRSF; PIRSF000138; Al-hdrx_acd_dh; 1.
DR   SUPFAM; SSF51395; FMN-linked oxidoreductases; 1.
DR   PROSITE; PS00557; FMN_HYDROXY_ACID_DH_1; 1.
DR   PROSITE; PS51349; FMN_HYDROXY_ACID_DH_2; 1.
DR   Genevisible; Q9WU19; MM.
PE   1: Evidence at protein level;
KW   Amino-acid biosynthesis; Flavoprotein; FMN; Oxidoreductase; Peroxisome;
KW   Phosphoprotein; Reference proteome.
FT   CHAIN           1..370
FT                   /note="2-Hydroxyacid oxidase 1"
FT                   /id="PRO_0000206319"
FT   DOMAIN          1..365
FT                   /note="FMN hydroxy acid dehydrogenase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT   MOTIF           368..370
FT                   /note="Microbody targeting signal"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        260
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT   BINDING         26
FT                   /ligand="glyoxylate"
FT                   /ligand_id="ChEBI:CHEBI:36655"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         79..81
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         108
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         130
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         132
FT                   /ligand="glyoxylate"
FT                   /ligand_id="ChEBI:CHEBI:36655"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         158
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         167
FT                   /ligand="glyoxylate"
FT                   /ligand_id="ChEBI:CHEBI:36655"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         236
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         258
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         260
FT                   /ligand="glyoxylate"
FT                   /ligand_id="ChEBI:CHEBI:36655"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         263
FT                   /ligand="glyoxylate"
FT                   /ligand_id="ChEBI:CHEBI:36655"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         291..295
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   BINDING         314..315
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
FT   MOD_RES         184
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         194
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         230
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJM8"
SQ   SEQUENCE   370 AA;  41001 MW;  97339211AF9FC19C CRC64;
     MLPRLVCISD YEQHVRSVLQ KSVYDYYRSG ANDQETLADN IQAFSRWKLY PRMLRNVADI
     DLSTSVLGQR VSMPICVGAT AMQCMAHVDG ELATVRACQT MGTGMMLSSW ATSSIEEVAE
     AGPEALRWMQ LYIYKDREIS RQIVKRAEKQ GYKAIFVTVD TPYLGNRIDD VRNRFKLPPQ
     LRMKNFETND LAFSPKGNFG DNSGLAEYVA QAIDPSLSWD DITWLRRLTS LPIVVKGILR
     GDDAKEAVKH GVDGILVSNH GARQLDGVPA TIDVLPEIVE AVEGKVEVFL DGGVRKGTDV
     LKALALGAKA VFVGRPIIWG LAFQGEKGVQ DVLEILKEEF RLAMALSGCQ NVKVIDKTLV
     RKNPLAVSKI
//