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

Names and origin

Protein names

Recommended name:
3-hydroxyanthranilate 3,4-dioxygenase
EC=1.13.11.6

Alternative name(s):
3-hydroxyanthranilate oxygenase
Short name=3-HAO
3-hydroxyanthranilic acid dioxygenase
Short name=HAD

Gene names

Name:

HAAO

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	286 AA.
Sequence status	Complete.
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; quinolinate from L-kynurenine: step 3/3. HAMAP-Rule MF_03019
Subunit structure	Monomer.
Subcellular location	Cytoplasm HAMAP-Rule MF_03019.
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 Reference proteome
Gene Ontology (GO)
Biological_process	NAD biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway neuron homeostasis Inferred from mutant phenotype PubMed 2967497. Source: UniProtKB quinolinate biosynthetic process Non-traceable author statement PubMed 12007609Ref.1. Source: UniProtKB response to cadmium ion Inferred from direct assay PubMed 12007609. Source: UniProtKB response to zinc ion Inferred from direct assay PubMed 12007609. Source: UniProtKB tryptophan catabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from direct assay Ref.1. Source: UniProtKB mitochondrial membrane Inferred from electronic annotation. Source: Compara
Molecular_function	3-hydroxyanthranilate 3,4-dioxygenase activity Inferred from direct assay PubMed 12007609Ref.1. Source: UniProtKB electron carrier activity Non-traceable author statement Ref.1. Source: UniProtKB ferrous iron binding Inferred from direct assay PubMed 12007609. Source: UniProtKB oxygen binding Inferred from electronic annotation. Source: Compara
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 HAMAP-Rule MF_03019

PRO_0000064372

Regions

Region

1 – 160

160

Domain A (catalytic) By similarity

Region

161 – 177

17

Linker By similarity

Region

178 – 286

109

Domain B By similarity

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

I → V. Ref.1 Ref.2 Ref.6
Corresponds to variant rs3816183 [ dbSNP | Ensembl ].

VAR_021507

Natural variant

42

1

T → S.
Corresponds to variant rs3816182 [ dbSNP | Ensembl ].

VAR_030470

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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 October 5, 2010. Version 2. Checksum: 4DA6AC20FC6EC885	FASTA	286	32,556
	10 20 30 40 50 60 MERRLGVRAW VKENRGSFQP PVCNKLMHQE QLKVMFIGGP 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 [UniParc]. Checksum: 3ABF821D6C31CE9E	FASTA	147	17,275
	10 20 30 40 50 60 MERRLGVRAW VKENRGSFQP PVCNKLMHQE QLKVMFIGGP 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, COFACTOR, VARIANT VAL-37.
[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), VARIANT VAL-37.
[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). 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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], VARIANT VAL-37.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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

EMBL
GenBank
DDBJ

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. NM_012205.2.

UniGene

Hs.368805.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P46952.

SMR

P46952. Positions 2-286.

ModBase

Search...

Protein-protein interaction databases

IntAct

P46952. 1 interaction.

MINT

MINT-1468803.

STRING

9606.ENSP00000294973.

PTM databases

PhosphoSite

P46952.

Polymorphism databases

DMDM

308153402.

Proteomic databases

PaxDb

P46952.

PRIDE

P46952.

Protocols and materials databases

DNASU

23498.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000294973; ENSP00000294973; ENSG00000162882.

GeneID

23498.

KEGG

hsa:23498.

UCSC

uc002rst.4. human.

Organism-specific databases

CTD

23498.

GeneCards

GC02M042994.

HGNC

HGNC:4796. HAAO.

HPA

HPA036394.

MIM

604521. gene.

neXtProt

NX_P46952.

PharmGKB

PA29171.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG77058.

HOGENOM

HOG000218448.

HOVERGEN

HBG000018.

InParanoid

P46952.

KO

K00452.

OMA

FYCKDLG.

OrthoDB

EOG4F4SBR.

Enzyme and pathway databases

BioCyc

MetaCyc:HS08749-MONOMER.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00253; UER00330.

Gene expression databases

ArrayExpress

P46952.

Bgee

P46952.

CleanEx

HS_HAAO.

Genevestigator

P46952.

GermOnline

ENSG00000162882. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.10. 2 hits.

HAMAP

MF_00825. 3_HAO.

InterPro

IPR010329. 3hydroanth_dOase.
IPR016700. 3hydroanth_dOase_met.
IPR014710. RmlC-like_jellyroll.
IPR011051. RmlC_Cupin.
[Graphical view]

Pfam

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

PIRSF

PIRSF017681. 3hydroanth_dOase_animal. 1 hit.

SUPFAM

SSF51182. RmlC_like_cupin. 2 hits.

TIGRFAMs

TIGR03037. anthran_nbaC. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

HAAO. human.

EvolutionaryTrace

P46952.

GenomeRNAi

23498.

NextBio

45867.

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:	October 5, 2010
Last modified:	April 3, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.