HAOX1_RAT
ID HAOX1_RAT Reviewed; 370 AA.
AC B0BNF9;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=2-Hydroxyacid oxidase 1 {ECO:0000305|PubMed:10777549};
DE Short=HAOX1 {ECO:0000303|PubMed:10777549};
DE EC=1.1.3.15 {ECO:0000250|UniProtKB:Q9UJM8};
DE AltName: Full=Glycolate oxidase {ECO:0000250|UniProtKB:Q9UJM8};
DE Short=GOX {ECO:0000250|UniProtKB:Q9UJM8};
DE AltName: Full=Glyoxylate oxidase {ECO:0000250|UniProtKB:Q9UJM8};
DE EC=1.2.3.5 {ECO:0000250|UniProtKB:Q9UJM8};
GN Name=Hao1 {ECO:0000312|RGD:1589750};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [4]
RP SUBCELLULAR LOCATION.
RX PubMed=10777549; DOI=10.1074/jbc.275.17.12590;
RA Jones J.M., Morrell J.C., Gould S.J.;
RT "Identification and characterization of HAOX1, HAOX2, and HAOX3, three
RT human peroxisomal 2-hydroxy acid oxidases.";
RL J. Biol. Chem. 275:12590-12597(2000).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16396499; DOI=10.1021/pr0503073;
RA Moser K., White F.M.;
RT "Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-
RT MS/MS.";
RL J. Proteome Res. 5:98-104(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Broad substrate specificity (S)-2-hydroxy-acid oxidase that
CC preferentially oxidizes glycolate. The glyoxylate produced by the
CC oxidation of glycolate can then be utilized by alanine-glyoxylate
CC aminotransferase for the peroxisomal synthesis of glycine; this pathway
CC appears to be an important step for the detoxification of glyoxylate
CC which, if allowed to accumulate, may be metabolized to oxalate with
CC formation of kidney stones. Can also catalyze the oxidation of
CC glyoxylate, and long chain hydroxyacids such as 2-hydroxyhexadecanoate
CC and 2-hydroxyoctanoate. Active in vitro with the artificial electron
CC acceptor 2,6-dichlorophenolindophenol (DCIP), but O2 is believed to be
CC the physiological electron acceptor, leading to the production of H2O2.
CC {ECO:0000250|UniProtKB:Q9UJM8}.
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:0000250|UniProtKB:Q9UJM8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16790;
CC Evidence={ECO:0000250|UniProtKB:Q9UJM8};
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:0000250|UniProtKB:Q9UJM8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25312;
CC Evidence={ECO:0000250|UniProtKB:Q9UJM8};
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:0000305|PubMed:10777549}.
CC -!- SIMILARITY: Belongs to the FMN-dependent alpha-hydroxy acid
CC dehydrogenase family. {ECO:0000255|PROSITE-ProRule:PRU00683}.
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DR EMBL; AABR07053812; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473949; EDL80285.1; -; Genomic_DNA.
DR EMBL; BC158804; AAI58805.1; -; mRNA.
DR RefSeq; NP_001101250.1; NM_001107780.2.
DR AlphaFoldDB; B0BNF9; -.
DR SMR; B0BNF9; -.
DR STRING; 10116.ENSRNOP00000006330; -.
DR BindingDB; B0BNF9; -.
DR ChEMBL; CHEMBL2021746; -.
DR CarbonylDB; B0BNF9; -.
DR PhosphoSitePlus; B0BNF9; -.
DR PaxDb; B0BNF9; -.
DR PeptideAtlas; B0BNF9; -.
DR PRIDE; B0BNF9; -.
DR Ensembl; ENSRNOT00000006330; ENSRNOP00000006330; ENSRNOG00000004601.
DR GeneID; 311446; -.
DR KEGG; rno:311446; -.
DR CTD; 54363; -.
DR RGD; 1589750; Hao1.
DR eggNOG; KOG0538; Eukaryota.
DR GeneTree; ENSGT00390000018717; -.
DR HOGENOM; CLU_020639_6_1_1; -.
DR InParanoid; B0BNF9; -.
DR OMA; FTRLMQT; -.
DR OrthoDB; 879633at2759; -.
DR PhylomeDB; B0BNF9; -.
DR TreeFam; TF313363; -.
DR Reactome; R-RNO-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-RNO-9033241; Peroxisomal protein import.
DR UniPathway; UPA00288; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Proteomes; UP000234681; Chromosome 3.
DR Bgee; ENSRNOG00000004601; Expressed in liver and 4 other tissues.
DR GO; GO:0005782; C:peroxisomal matrix; ISO:RGD.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0003973; F:(S)-2-hydroxy-acid oxidase activity; ISO:RGD.
DR GO; GO:0010181; F:FMN binding; ISO:RGD.
DR GO; GO:0047969; F:glyoxylate oxidase activity; ISO:RGD.
DR GO; GO:0001561; P:fatty acid alpha-oxidation; ISO:RGD.
DR GO; GO:0006545; P:glycine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046296; P:glycolate catabolic process; ISO:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IEP:RGD.
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_0000453972"
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:0000250|UniProtKB:Q9WU19"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WU19"
FT MOD_RES 230
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJM8"
SQ SEQUENCE 370 AA; 40968 MW; 2CFD33AFCF9021B0 CRC64;
MLPRLVCISD YEQHARTVLQ KSVYDYYKSG ANDQETLADN IRAFSRWKLY PRMLRNVADI
DLSTSVLGQR VSMPICVGAT AMQCMAHVDG ELATVRACQT MGTGMMLSSW ATSSIEEVAE
AGPEALRWMQ LYIYKDREVS SQLVKRAEQM GYKAIFVTVD TPYLGNRFDD VRNRFKLPPQ
LRMKNFETND LAFSPKGNFG DNSGLAEYVA QAIDPSLSWD DIKWLRRLTS LPIVVKGILR
GDDAQEAVKH GVDGILVSNH GARQLDGVPA TIDALPEIVE AVEGKVEVFL DGGVRKGTDV
LKALALGARA VFVGRPIIWG LAFQGEKGVQ DVLEILKEEF RLAMALSGCQ NVKVIDKTLV
RKNPLAVSKI
