3HAO_RAT
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 03-AUG-2022, entry version 148.
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;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03019,
CC 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; P46953; -.
DR PRIDE; P46953; -.
DR GeneID; 56823; -.
DR KEGG; rno:56823; -.
DR UCSC; RGD:71071; rat.
DR CTD; 23498; -.
DR RGD; 71071; Haao.
DR eggNOG; KOG3995; Eukaryota.
DR InParanoid; P46953; -.
DR OrthoDB; 1325876at2759; -.
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; IDA:RGD.
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; -; 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 PANTHER; PTHR15497; PTHR15497; 1.
DR Pfam; PF06052; 3-HAO; 1.
DR PIRSF; PIRSF017681; 3hydroanth_dOase_animal; 1.
DR SUPFAM; SSF51182; SSF51182; 2.
DR TIGRFAMs; TIGR03037; anthran_nbaC; 1.
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
