ID   3HAO_RAT                Reviewed;         286 AA.
AC   P46953; P70474; Q5RKK0; Q64556;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-1998, sequence version 2.
DT   08-NOV-2023, entry version 152.
DE   RecName: Full=3-hydroxyanthranilate 3,4-dioxygenase {ECO:0000255|HAMAP-Rule:MF_03019};
DE            EC=1.13.11.6 {ECO:0000255|HAMAP-Rule:MF_03019, ECO:0000269|PubMed:2940338};
DE   AltName: Full=3-hydroxyanthranilate oxygenase {ECO:0000255|HAMAP-Rule:MF_03019};
DE            Short=3-HAO {ECO:0000255|HAMAP-Rule:MF_03019};
DE   AltName: Full=3-hydroxyanthranilic acid dioxygenase {ECO:0000255|HAMAP-Rule:MF_03019};
DE            Short=HAD {ECO:0000255|HAMAP-Rule:MF_03019};
GN   Name=Haao;
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 [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=8541664; DOI=10.1271/bbb.59.2191;
RA   Nakagawa Y., Asai H., Mori H., Kitoh J., Nakano K.;
RT   "Increase in the level of mRNA for 3-hydroxyanthranilate 3,4-dioxygenase in
RT   brain of epilepsy-prone El mice.";
RL   Biosci. Biotechnol. Biochem. 59:2191-2192(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
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   PARTIAL NUCLEOTIDE SEQUENCE [MRNA] OF 44-236, AND PARTIAL PROTEIN SEQUENCE.
RX   PubMed=7514594; DOI=10.1016/s0021-9258(17)36717-0;
RA   Malherbe P., Kohler C., da Prada M., Lang G., Kiefer V., Schwarcz R.,
RA   Lahm H., Cesura A.M.;
RT   "Molecular cloning and functional expression of human 3-hydroxyanthranilic-
RT   acid dioxygenase.";
RL   J. Biol. Chem. 269:13792-13797(1994).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX   PubMed=2940338; DOI=10.1111/j.1471-4159.1986.tb02826.x;
RA   Foster A.C., White R.J., Schwarcz R.;
RT   "Synthesis of quinolinic acid by 3-hydroxyanthranilic acid oxygenase in rat
RT   brain tissue in vitro.";
RL   J. Neurochem. 47:23-30(1986).
CC   -!- FUNCTION: Catalyzes the oxidative ring opening of 3-hydroxyanthranilate
CC       to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes
CC       to quinolinate. {ECO:0000255|HAMAP-Rule:MF_03019,
CC       ECO:0000269|PubMed:2940338}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3-hydroxyanthranilate + O2 = (2Z,4Z)-2-amino-3-carboxymuconate
CC         6-semialdehyde; Xref=Rhea:RHEA:17953, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:36559, ChEBI:CHEBI:77612; EC=1.13.11.6;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03019,
CC         ECO:0000269|PubMed:2940338};
CC   -!- COFACTOR:
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03019, ECO:0000269|PubMed:2940338};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=3.6 uM for 3-hydroxyanthranilate {ECO:0000269|PubMed:2940338};
CC         Vmax=73.7 pmol/h/mg enzyme {ECO:0000269|PubMed:2940338};
CC   -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from
CC       L-kynurenine: step 3/3. {ECO:0000255|HAMAP-Rule:MF_03019}.
CC   -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_03019}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000255|HAMAP-
CC       Rule:MF_03019}.
CC   -!- SIMILARITY: Belongs to the 3-HAO family. {ECO:0000255|HAMAP-
CC       Rule:MF_03019}.
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DR   EMBL; D44494; BAA07937.1; -; mRNA.
DR   EMBL; BC085739; AAH85739.1; -; mRNA.
DR   EMBL; D28339; BAA21019.1; -; mRNA.
DR   RefSeq; NP_064461.1; NM_020076.2.
DR   AlphaFoldDB; P46953; -.
DR   SMR; P46953; -.
DR   IntAct; P46953; 4.
DR   STRING; 10116.ENSRNOP00000043835; -.
DR   BindingDB; P46953; -.
DR   ChEMBL; CHEMBL3108658; -.
DR   iPTMnet; P46953; -.
DR   PhosphoSitePlus; P46953; -.
DR   PaxDb; 10116-ENSRNOP00000043835; -.
DR   GeneID; 56823; -.
DR   KEGG; rno:56823; -.
DR   UCSC; RGD:71071; rat.
DR   AGR; RGD:71071; -.
DR   CTD; 23498; -.
DR   RGD; 71071; Haao.
DR   eggNOG; KOG3995; Eukaryota.
DR   InParanoid; P46953; -.
DR   OrthoDB; 2907058at2759; -.
DR   PhylomeDB; P46953; -.
DR   TreeFam; TF300246; -.
DR   Reactome; R-RNO-71240; Tryptophan catabolism.
DR   UniPathway; UPA00253; UER00330.
DR   PRO; PR:P46953; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:0031966; C:mitochondrial membrane; IDA:RGD.
DR   GO; GO:0000334; F:3-hydroxyanthranilate 3,4-dioxygenase activity; IDA:RGD.
DR   GO; GO:0008198; F:ferrous iron binding; ISO:RGD.
DR   GO; GO:0005506; F:iron ion binding; IDA:RGD.
DR   GO; GO:0019825; F:oxygen binding; IDA:RGD.
DR   GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IBA:GO_Central.
DR   GO; GO:0043420; P:anthranilate metabolic process; IEA:UniProtKB-UniRule.
DR   GO; GO:0009435; P:NAD biosynthetic process; ISO:RGD.
DR   GO; GO:0070050; P:neuron cellular homeostasis; ISO:RGD.
DR   GO; GO:0019805; P:quinolinate biosynthetic process; ISO:RGD.
DR   GO; GO:0046874; P:quinolinate metabolic process; IDA:RGD.
DR   GO; GO:0046686; P:response to cadmium ion; ISO:RGD.
DR   GO; GO:0010043; P:response to zinc ion; ISO:RGD.
DR   GO; GO:0006569; P:tryptophan catabolic process; IEA:UniProtKB-UniRule.
DR   CDD; cd06123; cupin_HAO; 1.
DR   Gene3D; 2.60.120.10; Jelly Rolls; 1.
DR   HAMAP; MF_00825; 3_HAO; 1.
DR   InterPro; IPR010329; 3hydroanth_dOase.
DR   InterPro; IPR016700; 3hydroanth_dOase_met.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   InterPro; IPR011051; RmlC_Cupin_sf.
DR   NCBIfam; TIGR03037; anthran_nbaC; 1.
DR   PANTHER; PTHR15497; 3-HYDROXYANTHRANILATE 3,4-DIOXYGENASE; 1.
DR   PANTHER; PTHR15497:SF1; 3-HYDROXYANTHRANILATE 3,4-DIOXYGENASE; 1.
DR   Pfam; PF06052; 3-HAO; 1.
DR   PIRSF; PIRSF017681; 3hydroanth_dOase_animal; 1.
DR   SUPFAM; SSF51182; RmlC-like cupins; 2.
PE   1: Evidence at protein level;
KW   Cytoplasm; Dioxygenase; Direct protein sequencing; Iron; Metal-binding;
KW   Oxidoreductase; Pyridine nucleotide biosynthesis; Reference proteome.
FT   CHAIN           1..286
FT                   /note="3-hydroxyanthranilate 3,4-dioxygenase"
FT                   /id="PRO_0000064374"
FT   REGION          1..160
FT                   /note="Domain A (catalytic)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   REGION          161..177
FT                   /note="Linker"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   REGION          178..286
FT                   /note="Domain B"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   BINDING         43
FT                   /ligand="O2"
FT                   /ligand_id="ChEBI:CHEBI:15379"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   BINDING         47
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   BINDING         53
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   BINDING         53
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   BINDING         91
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   BINDING         95
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   BINDING         105
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03019"
FT   CONFLICT        29
FT                   /note="R -> Q (in Ref. 2; AAH85739)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        44
FT                   /note="K -> S (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        199
FT                   /note="S -> F (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        204
FT                   /note="G -> C (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        214
FT                   /note="H -> Y (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        229
FT                   /note="W -> P (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   286 AA;  32582 MW;  B4F535AD8949DAB7 CRC64;
     MERCVRVKSW VEENRASFQP PVCNKLMHRE QLKIMFVGGP NTRKDYHIEE GEEVFYQLEG
     DMVLRVLEQG EHRDVVIRQG EIFLLPARVP HSPQRFANTM GLVIERRRME TELDGLRYYV
     GDTEDVLFEK WFHCKDLGTQ LAPIIQEFFH SEQYRTGKPN PDQLLKEPPF PLSTRSVMEP
     MSLKAWLESH SRELQAGTSL SLFGDSYETQ VIAHGQGSSK GPRQDVDVWL WQLEGSSKVT
     MGGQCVALAP DDSLLVPAGF SYMWERAQGS VALSVTQDPA CKKPLG
//