Reviewed, UniProtKB/Swiss-Prot P46952 (3HAO_HUMAN)

Names and origin

Protein names

Recommended name:
    3-hydroxyanthranilate 3,4-dioxygenase
    EC=1.13.11.6
Alternative name(s):
    3-hydroxyanthranilic acid dioxygenase
      Short name=HAD
    3-hydroxyanthranilate oxygenase
      Short name=3-HAO

Gene names

Name:

HAAO

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	286 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate. Ref.1
Catalytic activity	3-hydroxyanthranilate + O2 = 2-amino-3-carboxymuconate semialdehyde. Ref.1
Cofactor	Fe2+ ion. Ref.1
Pathway	Cofactor biosynthesis; NAD(+) biosynthesis; pyridine-2,3-dicarboxylate from L-kynurenine: step 3/3.
Subunit structure	Monomer.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the 3-HAO family.

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	NAD metabolic process Inferred from Experiment. Source: Reactome neuron maintenance Inferred from mutant phenotype. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW pyridine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW quinolinate biosynthetic process Ref.1 Non-traceable author statement. Source: UniProtKB response to cadmium ion Inferred from direct assay. Source: UniProtKB response to zinc ion Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Ref.1 Inferred from direct assay. Source: UniProtKB soluble fraction Inferred from direct assay. Source: UniProtKB
Molecular function	3-hydroxyanthranilate 3,4-dioxygenase activity Ref.1 Inferred from direct assay. Source: UniProtKB electron carrier activity Ref.1 Non-traceable author statement. Source: UniProtKB ferrous iron binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P46952-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P46952-2)

The sequence of this isoform differs from the canonical sequence as follows:
     148-286: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 286

286

3-hydroxyanthranilate 3,4-dioxygenase

PRO_0000064372

Sites

Metal binding

47

1

Iron; catalytic By similarity

Metal binding

53

1

Iron; catalytic By similarity

Metal binding

91

1

Iron; catalytic By similarity

Binding site

43

1

Dioxygen By similarity

Binding site

53

1

Substrate By similarity

Binding site

95

1

Substrate By similarity

Binding site

105

1

Substrate By similarity

Natural variations

Alternative sequence

148 – 286

139

Missing in isoform 2.

VSP_036239

Natural variant

37

1

V → I: dbSNP rs3816183. Ref.3 Ref.4 Ref.5 Ref.7

VAR_021507

Natural variant

42

1

T → S: dbSNP rs3816182.

VAR_030470

Secondary structure

1

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286

Helix Strand Turn

Details...

Beta strand

4 – 6

3

Helix

7 – 13

7

Helix

15 – 17

3

Turn

20 – 22

3

Beta strand

24 – 37

14

Beta strand

46 – 48

3

Beta strand

53 – 60

8

Beta strand

62 – 68

7

Beta strand

71 – 77

7

Beta strand

81 – 85

5

Beta strand

91 – 95

5

Beta strand

100 – 106

7

Beta strand

114 – 120

7

Beta strand

123 – 132

10

Helix

137 – 149

13

Helix

152 – 156

5

Helix

161 – 163

3

Helix

183 – 189

7

Helix

191 – 195

5

Beta strand

200 – 203

4

Beta strand

207 – 214

8

Beta strand

216 – 221

6

Beta strand

228 – 235

8

Beta strand

237 – 241

5

Beta strand

244 – 248

5

Beta strand

252 – 256

5

Beta strand

262 – 266

5

Beta strand

271 – 277

7

Helix

279 – 281

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 4DA10F20FC635885	FASTA	286	32,542
	10 20 30 40 50 60 MERRLGVRAW VKENRGSFQP PVCNKLMHQE QLKVMFVGGP NTRKDYHIEE GEEVFYQLEG 70 80 90 100 110 120 DMVLRVLEQG KHRDVVIRQG EIFLLPARVP HSPQRFANTV GLVVERRRLE TELDGLRYYV 130 140 150 160 170 180 GDTMDVLFEK WFYCKDLGTQ LAPIIQEFFS SEQYRTGKPI PDQLLKEPPF PLSTRSIMEP 190 200 210 220 230 240 MSLDAWLDSH HRELQAGTPL SLFGDTYETQ VIAYGQGSSE GLRQNVDVWL WQLEGSSVVT 250 260 270 280 MGGRRLSLAP DDSLLVLAGT SYAWERTQGS VALSVTQDPA CKKPLG
	Isoform 2. Checksum: EC64EFABA04007AF	FASTA	147	17,261
	10 20 30 40 50 60 MERRLGVRAW VKENRGSFQP PVCNKLMHQE QLKVMFVGGP NTRKDYHIEE GEEVFYQLEG 70 80 90 100 110 120 DMVLRVLEQG KHRDVVIRQG EIFLLPARVP HSPQRFANTV GLVVERRRLE TELDGLRYYV 130 140 GDTMDVLFEK WFYCKDLGTQ LAPIIQE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase." Malherbe P., Kohler C., da Prada M., Lang G., Kiefer V., Schwarcz R., Lahm H., Cesura A.M. J. Biol. Chem. 269:13792-13797(1994) [PubMed: 7514594] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, COFACTOR.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ILE-37. Tissue: Placenta.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ILE-37. Tissue: Hippocampus.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-37.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ILE-37. Tissue: Brain.
[8]	"Crystal structure of human 3-hydroxyanthranilate 3,4-dioxygenase." Center for eukaryotic structural genomics (CESG) Submitted (AUG-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH NICKEL IONS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z29481 mRNA. Translation: CAA82618.1.
CR457063 mRNA. Translation: CAG33344.1.
CR624693 mRNA. No translation available.
AK295693 mRNA. Translation: BAG58544.1.
AC098824 Genomic DNA. Translation: AAY14701.1.
CH471053 Genomic DNA. Translation: EAX00309.1.
BC029510 mRNA. Translation: AAH29510.1.

IPI

IPI00009375.
IPI00921062.

PIR

A54070.

RefSeq

NP_036337.2.

UniGene

Hs.368805

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QNK	X-ray	1.60	A	2-286	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P46952. 1 interaction.

PTM databases

PhosphoSite

P46952.

Proteomic databases

PRIDE

P46952.

Genome annotation databases

Ensembl

ENSG00000162882. Homo sapiens. [Contig view]

GeneID

23498.

KEGG

hsa:23498.

UCSC

uc002rst.2. human.

Organism-specific databases

GeneCards

GC02M042847.

H-InvDB

HIX0018978.

HGNC

HGNC:4796. HAAO.

MIM

604521. gene.

PharmGKB

PA29171.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P46952.

HOVERGEN

P46952.

Enzyme and pathway databases

BRENDA

1.13.11.6. 247.

Reactome

REACT_11193. Metabolism of vitamins and cofactors.
REACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpress

P46952.

Bgee

P46952.

CleanEx

HS_HAAO.

GermOnline

ENSG00000162882. Homo sapiens.

Family and domain databases

InterPro

IPR010329. 3hydroanth_dOase.
IPR016700. 3hydroanth_dOase_met.
[Graphical view]

Pfam

PF06052. 3-HAO. 1 hit.
[Graphical view]

PIRSF

PIRSF017681. 3hydroanth_dOase_animal. 1 hit.

TIGRFAMs

TIGR03037. anthran_nbaC. 1 hit.

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

3HAO_HUMAN

Accession

Primary (citable) accession number: P46952
Secondary accession number(s): A6NE56 , B4DIN2, Q53QZ7, Q8N6N9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	July 7, 2009
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)