HAOX1_MOUSE
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 03-AUG-2022, entry version 155.
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; Q9WU19; -.
DR PRIDE; Q9WU19; -.
DR ProteomicsDB; 269712; -.
DR Antibodypedia; 8448; 411 antibodies from 32 providers.
DR DNASU; 15112; -.
DR Ensembl; ENSMUST00000028704; ENSMUSP00000028704; ENSMUSG00000027261.
DR GeneID; 15112; -.
DR KEGG; mmu:15112; -.
DR UCSC; uc008mns.1; mouse.
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; FTRLMQT; -.
DR OrthoDB; 879633at2759; -.
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 73 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 tissues.
DR ExpressionAtlas; Q9WU19; baseline and differential.
DR Genevisible; Q9WU19; MM.
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; -; 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 Pfam; PF01070; FMN_dh; 1.
DR PIRSF; PIRSF000138; Al-hdrx_acd_dh; 1.
DR PROSITE; PS00557; FMN_HYDROXY_ACID_DH_1; 1.
DR PROSITE; PS51349; FMN_HYDROXY_ACID_DH_2; 1.
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
