Information on EC 1.13.11.5 -

Information on EC 1.13.11.5 - homogentisate 1,2-dioxygenase:

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EC NUMBER	COMMENTARY
1.13.11.5	-

RECOMMENDED NAME	GeneOntology No.
homogentisate 1,2-dioxygenase	GO:0004411

REACTION	REACTION DIAGRAM	COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
homogentisate + O2 = 4-maleylacetoacetate		-	-	-	-
homogentisate + O2 = 4-maleylacetoacetate		catalytic mechanism	Homo sapiens	-	439392

REACTION TYPE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
oxidation	-	-	-	-
redox reaction	-	-	-	-
reduction	-	-	-	-

PATHWAY	KEGG Link	MetaCyc Link
tyrosine degradation I	-	TYRFUMCAT-PWY

SYSTEMATIC NAME	IUBMB Comments
homogentisate:oxygen 1,2-oxidoreductase (decyclizing)	Requires Fe2+.

SYNONYMS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
EC 1.13.1.5	-	-	formerly	-
EC 1.99.2.5	-	-	formerly	-
ElHDO	Exophiala lecanii-corni	Q6JDV6	-	657627
HgD	Homo sapiens	-	-	674157, 697403, 712909
HgD	Bos taurus	-	-	712929, 712990
HGO	-	-	-	-
HGO	Homo sapiens	-	-	657859
HGO	Arabidopsis thaliana	Q9ZRA2	-	670622
HGO	Phanerochaete chrysosporium	-	-	670853
HGOa	Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera	-	-	706809
HGOb	Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera	-	-	706809
HmgA	Pseudomonas putida	-	-	677068
HmgA	Pseudomonas aeruginosa	-	-	686387
HmgA	Streptomyces coelicolor	-	-	686802
homogentisate 1,2-dioxygenase	Homo sapiens	-	-	697403
homogentisate 1,2-dioxygenase	Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera	-	-	706809
homogentisate dioxygenase	-	-	-	-
homogentisate dioxygenase	Arabidopsis thaliana	Q9ZRA2	-	670622
homogentisate dioxygenase	Phanerochaete chrysosporium	-	-	670853
homogentisate dioxygenase	Homo sapiens	-	-	674157
homogentisate oxidase	-	-	-	-
homogentisate oxygenase	-	-	-	-
homogentisate phytyl-transferase	Cistus creticus	-	involved in isoprenoid biosynthetic pathway	699799
homogentisic acid 1,2-dioxygenase	Homo sapiens	-	-	712909
homogentisic acid oxidase	-	-	-	-
homogentisic acid oxygenase	-	-	-	-
homogentisic oxygenase	-	-	-	-
homogentisicase	-	-	-	-
HPT	Cistus creticus	-	-	699799
HTO	-	-	-	-

CAS REGISTRY NUMBER	COMMENTARY
9029-49-6	-

ORGANISM	COMMENTARY	LITERATURE	SEQUENCE CODE	SEQUENCE DB	SOURCE
Agave toumeyana	-	439385	-	-
Agrostemma githago	-	439385	-	-
Arabidopsis thaliana	-	670622	Q9ZRA2	SwissProt
Aspergillus niger	UBC 814	439386	-	-
Bos taurus	-	396333, 439390, 439392	-	-
Bos taurus	-	712929	B8YB76	UniProt
Bos taurus	gene HGD	712990	B8YB76	UniProt
Bos taurus Chinese red cattle	-	712929	B8YB76	UniProt
Cavia porcellus	-	439383	-	-
Cistus creticus	-	699799	-	-
Daucus carota	-	439385	-	-
Drosophyllum lusitanicum	-	439385	-	-
Emericella nidulans	filamentous ascomycete; strain biA1	439391	Q00667	Uniprot
Emericella nidulans	filamentous ascomycete; strains biA1 and veA1	439389	-	-
Emericella nidulans BiA1	strain biA1	439391	Q00667	-
Exophiala lecanii-corni	-	657627	Q6JDV6	SwissProt
Glycine max	-	439385	-	-
Homo sapiens	-	439387, 674157, 697403	Q93099	Uniprot
Homo sapiens	-	439390, 439392, 657859, 712561, 712909, 712935	-	-
Melilotus albus	-	439385	-	-
Mus musculus	-	439388, 439392, 439393	-	-
Mus musculus	normal and alkaptonuric mice, which completely lack HTO	439390	-	-
Nicotiana sylvestris	-	439385	-	-
Oryctolagus cuniculus	-	439383	-	-
Oryctolagus cuniculus	male rabbits	439390	-	-
Phanerochaete chrysosporium	-	670853	-	-
Phaseolus vulgaris	var. nanus	439385	-	-
Pigeon	-	439383	-	-
Pimpinella anisum	-	439385	-	-
Pseudomonas aeruginosa	synthesis of homogentisate-1,2-dioxygenase (HmgA) is highly induced in anaerobic norCB bacteria, and not detected in wild-type extracts	686387	-	-
Pseudomonas chlororaphis	strain O6	686266	-	-
Pseudomonas fluorescens	-	396333, 439380	-	-
Pseudomonas putida	strain KT 2440	677068	-	-
Rattus norvegicus	-	439381, 439382, 439383	-	-
Ruta graveolens	-	439385	-	-
Solenostemon scutellarioides	-	439385	-	-
Streptomyces coelicolor	-	686802	-	-
Vitis vinifera x Vitis riparia	-	706809	-	-
Vitis vinifera x Vitis vinifera	-	706809	-	-

GENERAL INFORMATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
evolution	Homo sapiens	-	the G161R natural mutation in the HGD gene occurs in a Hungarian population, originating from Slovakia, resists over 300 years, alkaptonuria phenotype overview	712909
malfunction	Homo sapiens	-	alkaptonuria is a rare autosomal recessive disease, associated with deficiency of homogentisate 1,2-dioxygenase activity in the liver. This leads to an accumulation of homogentisic acid and its oxidized derivatives in polymerized form in connective tissues, especially in joints. Homogentisic acid induces apoptosis in chondrocytes. N-acetylcysteine decreases apoptosis induced in chondrocytes by HGA, increases chondrocyte growth reduced by homogentisate, and partially restores proteoglycan release inhibited by homogentisate, the effect is improved by addition of ascorbic acid. Evaluation of antioxidant drugs for the treatment of ochronotic alkaptonuria, caused by homogentisate 1,2-dioxygenase activity mutation, in an in vitro human cell model, overview	712561
physiological function	Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera	-	involved in aromatic amino acid metabolism	706809
metabolism	Homo sapiens	-	the enzyme is involved in tyrosine catabolism	712935
additional information	Bos taurus	B8YB76	HGD-BstXI genotypes show significant effects on cooking loss, drip loss, net meat weight, carcass weight, and eye muscle area. Also the HGD-HaeIII genotypes significantly affect cooking loss, muscle fibre diameter, shear force, drip loss, and carcass yield ratio. Phenotypes, overview	712929
additional information	Homo sapiens	-	mutations in homogentisate 1,2-dioxygenase cause alkaptonuria and subsequent ochronosis, an uncommon cause of backache. The phenotype includes limited spine mobility and chronic disk degeneration, overview	712935

SUBSTRATE	PRODUCT	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY/ Substrate	LITERATURE/ Substrate	COMMENTARY/ Product	LITERATURE/ Product	Reversibility r=reversible ir=irreversible ?=not specified
3-chlorohomogentisate + O2	3-chloro-4-maleylacetoacetate		Homo sapiens	-	1% of activity with homogentisate	657859	-	-	?
3-methylhomogentisate + O2	3-methyl-4-maleylacetoacetate		Homo sapiens	-	10% of activity with homogentisate	657859	-	-	?
homogentisate + O2	4-maleylacetoacetate		Phaseolus vulgaris	-	-	439385	-	439385	?
homogentisate + O2	4-maleylacetoacetate		Mus musculus	-	-	439388	-	439388	?
homogentisate + O2	4-maleylacetoacetate		Mus musculus	-	-	439390	-	439390	?
homogentisate + O2	4-maleylacetoacetate		Mus musculus	-	-	439392	-	439392	?
homogentisate + O2	4-maleylacetoacetate		Mus musculus	-	-	439393	-	439393	ir
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	Q93099	-	439387	-	439387	?
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	-	-	439390	-	439390	?
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	-	-	657859, 697403	-	-	?
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	-	-	674157	-	-	ir
homogentisate + O2	4-maleylacetoacetate		Oryctolagus cuniculus	-	-	439390	-	439390	?
homogentisate + O2	4-maleylacetoacetate		Emericella nidulans	Q00667	-	439391	-	439391	?
homogentisate + O2	4-maleylacetoacetate		Glycine max	-	-	439385	-	439385	?
homogentisate + O2	4-maleylacetoacetate		Pseudomonas fluorescens	-	-	396333	-	396333	?
homogentisate + O2	4-maleylacetoacetate		Pseudomonas putida	-	-	677068	-	-	ir
homogentisate + O2	4-maleylacetoacetate		Daucus carota, Nicotiana sylvestris, Ruta graveolens	-	-	439385	-	439385	?
homogentisate + O2	4-maleylacetoacetate		Phanerochaete chrysosporium	-	-	670853	-	-	ir
homogentisate + O2	4-maleylacetoacetate		Melilotus albus, Solenostemon scutellarioides, Agrostemma githago, Agave toumeyana, Drosophyllum lusitanicum, Pimpinella anisum	-	-	439385	-	439385	?
homogentisate + O2	4-maleylacetoacetate		Arabidopsis thaliana	Q9ZRA2	-	670622	-	-	ir
homogentisate + O2	4-maleylacetoacetate		Rattus norvegicus	-	-	439382	product is 4-maleylacetoacetate, which is converted by a specific cis-trans isomerase to 4-fumarylacetoacetate	439382	?
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	-	utilizes a nonheme iron to incorporate both atoms of molecular oxygen into homogentisate, identical with 2,5-dihydroxyphenylacetate	439392	-	439392	?
homogentisate + O2	4-maleylacetoacetate		Emericella nidulans	-	highly specific for homogentisate	439389	-	439389	?
homogentisate + O2	4-maleylacetoacetate		Aspergillus niger	-	specific for homogentisate	439386	-	439386	?
homogentisate + O2	4-maleylacetoacetate		Pseudomonas fluorescens	-	specific for homogentisate	439380	-	439380	?
homogentisate + O2	4-maleylacetoacetate		Mus musculus	-	homogentisate is the natural substrate, key reaction in the catabolic pathway of aromatic amino acids, oxidative cleavage of the aromatic ring	439393	-	439393	ir
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	-	enzyme catalyzes an intermediate step in the catabolism of tyrosine and phenylalanine	439390	-	-	?
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	-	enzyme cleaves the aromatic ring during the metabolic degradation of phenylalanine and tyrosine	439392	-	-	?
homogentisate + O2	4-maleylacetoacetate		Mus musculus	-	homogentisate catabolism	439388	-	-	?
homogentisate + O2	4-maleylacetoacetate		Phaseolus vulgaris, Glycine max, Daucus carota, Nicotiana sylvestris, Ruta graveolens, Melilotus albus, Solenostemon scutellarioides, Agrostemma githago, Agave toumeyana, Drosophyllum lusitanicum, Pimpinella anisum	-	homogentisate ring-cleavage pathway, key enzyme of the ring-cleavage reaction in the catabolic sequence of enzymes from L-tyrosine to acetoacetate and fumarate	439385	-	-	?
homogentisate + O2	4-maleylacetoacetate		Aspergillus niger	-	one of the key enzymes involved in catabolism of phenylalanine, tyrosine, phenylacetic acid and hydroxyphenylacetic acids	439386	-	-	?
homogentisate + O2	4-maleylacetoacetate		Emericella nidulans	-	one of the enzymes mediating phenylalanine catabolism	439389	-	-	?
homogentisate + O2	4-maleylacetoacetate		Emericella nidulans	Q00667	catalyzes an essential step in phenylalanine catabolism	439391	-	-	?
homogentisate + O2	4-maleylacetoacetate		Exophiala lecanii-corni	Q6JDV6	ElHDO expression is induced during growth on ethylbenzene	657627	-	-	?
homogentisate + O2	4-maleylacetoacetate		Streptomyces coelicolor	-	hmgA is necessary for tyrosine catabolism and the proper production of actinorhodin. Transcription of hmgA is activated by HpdA in the presence of tyrosine	686802	-	-	?
homogentisate + O2	4-fumarylacetoacetate		Cavia porcellus, Rattus norvegicus, Oryctolagus cuniculus, Pigeon	-	-	439383	-	439383	?
homogentisate + O2	4-fumarylacetoacetate		Rattus norvegicus	-	homogentisic acid is oxidatively cleaved between carbons 1 and 2 to yield 4-fumarylacetoacetic acid, enzyme requires high oxygen tension for maximal activity	439381	-	439381	?
additional information	?	-	Pseudomonas fluorescens	-	not as substrates: salicylic acid, catechol, 2,3-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, 2,6-dihydroxybenzoic acid, o-hydroxyphenylacetic acid, p-hydroxyphenylacetic acid, 3,4-dihydroxyphenylacetic acid	439380	-	-	-
additional information	?	-	Rattus norvegicus	-	enzyme contains essential sulfhydryl groups	439382	-	-	-
additional information	?	-	Emericella nidulans	-	not as substrates: phenylacetate, 2-hydroxyphenylacetate, 3-hydroxyphenylacetate, 4-hydroxyphenylacetate, phenylalanine, tyrosine, phenylpyruvate, gentisate	439389	-	-	-
additional information	?	-	Homo sapiens	-	enzyme structure, conformation of the active site, enzyme contains a 280-residue N-terminal domain and a 140-residue C-terminal domain, associated as a hexamer arranged as a dimer of trimers	439392	-	-	-
additional information	?	-	Arabidopsis thaliana	Q9ZRA2	gentisate is not a substrate	670622	-	-	-
additional information	?	-	Pseudomonas chlororaphis	-	growth of the hmgA mutant on L-tyrosine as sole carbon and energy sources is impaired. Growth on L-tyrosine is restored and production of the brown melanin pigment is eliminated when the mutant is complemented with the wild-type hmgA gene. The change in aromatic amino acids metabolism caused by the deletion of the hmgA gene function does not impair production of phenazines and biological traits connected to these secondary compounds: inhibition of fungal growth and inhibition of barley seed germination	686266	-	-	-

NATURAL SUBSTRATES	NATURAL PRODUCTS	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY SUBSTRATE	LITERATURE (Substrate)	COMMENTARY PRODUCT	LITERATURE (Product)
homogentisate + O2	4-maleylacetoacetate		Mus musculus	-	-	439390, 439392	-	-
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	-	-	657859, 697403	-	-
homogentisate + O2	4-maleylacetoacetate		Mus musculus	-	homogentisate is the natural substrate, key reaction in the catabolic pathway of aromatic amino acids, oxidative cleavage of the aromatic ring	439393	-	439393
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	-	enzyme catalyzes an intermediate step in the catabolism of tyrosine and phenylalanine	439390	-	-
homogentisate + O2	4-maleylacetoacetate		Homo sapiens	-	enzyme cleaves the aromatic ring during the metabolic degradation of phenylalanine and tyrosine	439392	-	-
homogentisate + O2	4-maleylacetoacetate		Mus musculus	-	homogentisate catabolism	439388	-	-
homogentisate + O2	4-maleylacetoacetate		Phaseolus vulgaris, Glycine max, Daucus carota, Nicotiana sylvestris, Ruta graveolens, Melilotus albus, Solenostemon scutellarioides, Agrostemma githago, Agave toumeyana, Drosophyllum lusitanicum, Pimpinella anisum	-	homogentisate ring-cleavage pathway, key enzyme of the ring-cleavage reaction in the catabolic sequence of enzymes from L-tyrosine to acetoacetate and fumarate	439385	-	-
homogentisate + O2	4-maleylacetoacetate		Aspergillus niger	-	one of the key enzymes involved in catabolism of phenylalanine, tyrosine, phenylacetic acid and hydroxyphenylacetic acids	439386	-	-
homogentisate + O2	4-maleylacetoacetate		Emericella nidulans	-	one of the enzymes mediating phenylalanine catabolism	439389	-	-
homogentisate + O2	4-maleylacetoacetate		Emericella nidulans	Q00667	catalyzes an essential step in phenylalanine catabolism	439391	-	-
homogentisate + O2	4-maleylacetoacetate		Streptomyces coelicolor	-	hmgA is necessary for tyrosine catabolism and the proper production of actinorhodin. Transcription of hmgA is activated by HpdA in the presence of tyrosine	686802	-	-
additional information	?	-	Pseudomonas chlororaphis	-	growth of the hmgA mutant on L-tyrosine as sole carbon and energy sources is impaired. Growth on L-tyrosine is restored and production of the brown melanin pigment is eliminated when the mutant is complemented with the wild-type hmgA gene. The change in aromatic amino acids metabolism caused by the deletion of the hmgA gene function does not impair production of phenazines and biological traits connected to these secondary compounds: inhibition of fungal growth and inhibition of barley seed germination	686266	-	-

COFACTOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
ascorbate	Arabidopsis thaliana	Q9ZRA2	-	670622	2D-image

METALS and IONS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
Fe2+	Pseudomonas fluorescens	-	Fe2+ is required as cofactor	396333, 439380
Fe2+	Bos taurus	-	ferrous ion is required for maximal activity at pH 7 and pH 5.3; ferrous mercaptans at the active center	396333
Fe2+	Rattus norvegicus	-	contains non-porphyrin iron, valence change of enzymic iron during reaction: ferric and ferrous iron	439382
Fe2+	Aspergillus niger	-	requires Fe2+	439386
Fe2+	Emericella nidulans	-	dependent on the presence of Fe2+	439389
Fe2+	Emericella nidulans	Q00667	70% reduction of enzyme activity in crude extract in absence of Fe2+ and absolutely requirement for Fe2+ of the fusion protein of homogentisate dioxygenase and glutathione S-transferase, expressed in Escherichia coli	439391
Fe2+	Bos taurus	-	-	439392
Fe2+	Homo sapiens	-	contains a nonheme Fe2+ at the active site, that is coordinated near the interface between subunits in the HGO trimer by Glu-341, His-335 and His-371	439392
Fe2+	Mus musculus	-	-	439392
Fe2+	Mus musculus	-	Fe2+ is an absolutely obligate cofactor and cannot be replaced by other divalent cations, highest enzyme activity in vitro at 2 mM Fe2+	439393
Fe2+	Homo sapiens	-	required for activity	657859
Fe2+	Arabidopsis thaliana	Q9ZRA2	-	670622
Fe2+	Homo sapiens	-	required	674157
additional information	Pseudomonas fluorescens	-	other metallic ions, such as Fe3+, Co2+, Mn2+, Cu+ and Cu2+, cannot replace Fe2+	439380
additional information	Mus musculus	-	Fe3+ cannot replace Fe2+	439393

INHIBITORS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
1,10-phenanthroline	Homo sapiens	-	inactivation in the absence of O2 due to formation of a white precipitate corresponding to apoprotein	657859	2D-image
2,2'-dipyridyl	Rattus norvegicus	-	complete inhibition	439382	2D-image
2,2'-dipyridyl	Drosophyllum lusitanicum	-	5 mM, complete inhibition	439385	2D-image
2-hydroxyphenylacetate	Aspergillus niger	-	strong competitive inhibition with respect to homogentisate	439386	2D-image
2-mercaptoethanol	Pseudomonas fluorescens	-	-	439380	2D-image
3,4-Dihydroxyphenylacetate	Emericella nidulans	-	1 mM, 48% inhibition, substrate analogue	439389	2D-image
3-chlorohomogentisate	Homo sapiens	-	inactivation in the presence of O2 due to formation of a white precipitate corresponding to apoprotein	657859	2D-image
3-hydroxyphenylacetate	Aspergillus niger	-	competitive inhibition with respect to homogentisate	439386	2D-image
ascorbate	Mus musculus	-	strong inhibitory effect, but stabilizes	439393	2D-image
ascorbic acid	Homo sapiens	-	38% inhibition at pH 6.2	657859	2D-image
azide	Rattus norvegicus	-	-	439382	2D-image
benzoquinoneacetic acid	Rattus norvegicus	-	-	439382	-
CaCl2	Oryctolagus cuniculus	-	0.001 mM, 56% inhibition	439390	2D-image
Co2+	Mus musculus	-	incubation with Fe2+ plus Co2+ in equimolar concentrations inhibits	439393	2D-image
Cu2+	Mus musculus	-	incubation with Fe2+ plus Cu2+ in equimolar concentrations inhibits	439393	2D-image
cyanide	Rattus norvegicus	-	3 mM inhibits	439381	2D-image
cyanide	Rattus norvegicus	-	-	439382	2D-image
cysteic acid	Rattus norvegicus	-	weak inhibition	439382	2D-image
cysteine	Rattus norvegicus	-	inhibition not reversed by glutathione	439382	2D-image
cystine	Rattus norvegicus	-	inhibition not reversed by glutathione	439382	2D-image
diphosphate	Rattus norvegicus	-	-	439382	2D-image
FeSO4	Homo sapiens	-	0.25 mM, 42% inhibition	657859	2D-image
glutathione	Mus musculus	-	reduced glutathione slightly inhibits	439393	2D-image
Hg2+	Rattus norvegicus	-	inhibition reversed by glutathione	439382	2D-image
HgCl2	Oryctolagus cuniculus	-	20 mM, complete inhibition	439390	2D-image
Lewisite	Bos taurus	-	inhibits by competing with Fe2+ for a common enzymic binding site	396333	2D-image
NaCl	Oryctolagus cuniculus	-	0.001 mM, 63% inhibition	439390	2D-image
Ni2+	Mus musculus	-	incubation with Fe2+ plus Ni2+ in equimolar concentrations inhibits	439393	2D-image
p-chloromercuribenzoate	Pseudomonas fluorescens	-	competitive inhibition with respect to Fe2+ but not to homogentisate	396333, 439380	2D-image
p-chloromercuribenzoate	Bos taurus	-	inhibits by competing with Fe2+ for a common enzymic binding site	396333	2D-image
p-chloromercuribenzoate	Rattus norvegicus	-	inhibition reversed by glutathione	439382	2D-image
p-hydroxyphenylacetic acid	Oryctolagus cuniculus	-	80 mM, complete inhibition, substrate analogue	439390	2D-image
p-hydroxyphenylpyruvate	Emericella nidulans	-	1 mM, 68% inhibition, substrate analogue	439389	2D-image
phosphate	Rattus norvegicus	-	-	439382	2D-image
Sulfhydryl reagents	Aspergillus niger	-	strong inhibition	439386	2D-image
Superoxide dismutase	Aspergillus niger	-	inhibits the reaction indicating the involvement of superoxide anions in the dioxygenase reaction	439386	-
Zn2+	Mus musculus	-	incubation with Fe2+ plus Zn2+ in equimolar concentrations inhibits	439393	2D-image
Methylmercuric bromide	Bos taurus	-	inhibits by competing with Fe2+ for a common enzymic binding site	396333	2D-image
additional information	Mus musculus	-	not inhibited by Ca2+ and Mn2+	439393	-

ACTIVATING COMPOUND	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
4-Hydroxy-3-methoxybenzaldehyde	Phanerochaete chrysosporium	-	2 mM	670853	2D-image
ascorbate	Pseudomonas fluorescens	-	required for maximal activity at pH 6	396333, 439380	2D-image
ascorbate	Bos taurus	-	required for maximal activity at pH 7	396333	2D-image
ascorbate	Rattus norvegicus	-	activates	439382	2D-image
ascorbate	Emericella nidulans	-	dependent on the presence of ascorbate, presumably to maintain iron in the reduced form	439389	2D-image
cysteine	Pseudomonas fluorescens	-	activates	439380	2D-image
cysteine	Rattus norvegicus	-	activates	439382	2D-image
glutathione	Pseudomonas fluorescens	-	required for maximal activity at pH 6 and 5.4	396333, 439380	2D-image
glutathione	Bos taurus	-	reduced glutathione is required for maximal activity at pH 7	396333	2D-image
glutathione	Rattus norvegicus	-	activates	439382	2D-image
additional information	Bos taurus	-	pH 7.0: a combination of ascorbate, reduced glutathione and ferrous iron is required for activation, pH 5.3: ferrous iron alone fully activates	396333	-
additional information	Emericella nidulans	-	enzymes of phenylalanine catabolism including HGO are strongly induced by the presence of phenylalanine or phenylacetate	439389	-
additional information	Emericella nidulans	Q00667	fusion protein of homogentisate dioxygenase and glutathione S-transferase, expressed in Escherichia coli is fully active in absence of ascorbate	439391	-
additional information	Cistus creticus	-	induced gene expression by water deficit	699799	-

KM VALUE [mM]	KM VALUE [mM] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.009	-	Homogentisate	Emericella nidulans	-	-	439389	2D-image
0.009	-	Homogentisate	Homo sapiens	-	25�C, pH 8.0	657859	2D-image
0.01	-	Homogentisate	Oryctolagus cuniculus	-	-	439390	2D-image
0.014	-	Homogentisate	Homo sapiens	-	37�C, pH 7.0	657859	2D-image
0.015	-	Homogentisate	Homo sapiens	-	37�C, pH 6.2	657859	2D-image
0.016	-	Homogentisate	Homo sapiens	-	25�C, pH 7.0	657859	2D-image
0.022	-	Homogentisate	Homo sapiens	-	25�C, pH 6.2	657859	2D-image
0.031	-	Homogentisate	Arabidopsis thaliana	Q9ZRA2	in the absence of ascorbate and Fe2+	670622	2D-image
0.042	-	Homogentisate	Homo sapiens	-	25�C, pH 5.5	657859	2D-image
0.188	-	Homogentisate	Mus musculus	-	-	439393	2D-image
0.6	-	Homogentisate	Pseudomonas fluorescens	-	at pH 6	396333, 439380	2D-image
0.6	-	Homogentisate	Aspergillus niger	-	-	439386	2D-image

TURNOVER NUMBER [1/s]	TURNOVER NUMBER MAXIMUM[1/s]	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.53	-	3-chlorohomogentisate	Homo sapiens	-	25�C, pH 6.2	657859	2D-image
5.3	-	3-methylhomogentisate	Homo sapiens	-	25�C, pH 6.2	657859	2D-image
10.1	-	Homogentisate	Homo sapiens	-	25�C, pH 8.0	657859	2D-image
32.2	-	Homogentisate	Homo sapiens	-	25�C, pH 7.0	657859	2D-image
41.5	-	Homogentisate	Homo sapiens	-	25�C, pH 5.5	657859	2D-image
43.4	-	Homogentisate	Homo sapiens	-	37�C, pH 7.0	657859	2D-image
56	-	Homogentisate	Homo sapiens	-	25�C, pH 6.2	657859	2D-image
64.3	-	Homogentisate	Homo sapiens	-	37�C, pH 6.2	657859	2D-image

kcat/KM VALUE [1/mMs^-1]	kcat/KM VALUE [1/mMs^-1] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

Ki VALUE [mM]	Ki VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

IC50 VALUE [mM]	IC50 VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

SPECIFIC ACTIVITY [µmol/min/mg]	SPECIFIC ACTIVITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
0.125	-	Melilotus albus	-	-	439385
0.17	-	Pimpinella anisum	-	-	439385
0.25	-	Daucus carota	-	-	439385
0.39	-	Ruta graveolens	-	-	439385
0.405	-	Agrostemma githago	-	-	439385
0.495	-	Glycine max	-	-	439385
0.515	-	Phaseolus vulgaris	-	-	439385
0.625	-	Agave toumeyana	-	-	439385
0.75	1	Emericella nidulans	-	value in crude lysates	439389
1.16	-	Nicotiana sylvestris	-	-	439385
2.59	-	Solenostemon scutellarioides	-	-	439385
5.17	-	Aspergillus niger	-	-	439386
8.25	-	Pseudomonas fluorescens	-	-	439380
28.3	-	Homo sapiens	-	recombinant HGO	657859
additional information	-	Drosophyllum lusitanicum	-	-	439385
additional information	-	Mus musculus, Oryctolagus cuniculus	-	-	439390
additional information	-	Mus musculus	-	-	439393

pH OPTIMUM	pH MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
5	-	Oryctolagus cuniculus	-	-	439390
6	-	Pseudomonas fluorescens	-	-	439380
6.1	-	Mus musculus	-	-	439393
6.2	-	Homo sapiens	-	Good buffer	657859
6.4	-	Aspergillus niger	-	-	439386
6.5	7	Emericella nidulans	-	-	439389

pH RANGE	pH RANGE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
5	8	Homo sapiens	-	approx. 15% of maximal activity at pH 5.0 and pH 8.0, respectively	657859

TEMPERATURE OPTIMUM	TEMPERATURE OPTIMUM MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
30	-	Pseudomonas fluorescens	-	assay at	439380
30	-	Oryctolagus cuniculus	-	-	439390
38	-	Rattus norvegicus	-	assay at	439381

TEMPERATURE RANGE	TEMPERATURE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

pI VALUE	pI VALUE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
5.74	-	Pseudomonas putida	-	calculated value	677068
6.7	-	Phanerochaete chrysosporium	-	theoretical value	670853

SOURCE TISSUE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	SOURCE
bone	Homo sapiens	-	-	712909, 712935
brain	Mus musculus	-	expression of HGO gene	439388
chondrocyte	Homo sapiens	-	-	712561
colon	Homo sapiens	-	-	439387
embryo	Homo sapiens	-	liver from a 20 week old male embryo	439390
flower	Arabidopsis thaliana	Q9ZRA2	-	670622
heart	Mus musculus	-	expression of HGO gene	439388
kidney	Cavia porcellus, Oryctolagus cuniculus, Pigeon	-	less activity than in liver or in rat kidney	439383
kidney	Rattus norvegicus	-	40% of enzyme activity in liver	439383
kidney	Homo sapiens	-	-	439387
kidney	Mus musculus	-	expression of HGO gene	439388
kidney	Bos taurus	B8YB76	-	712990
leaf	Arabidopsis thaliana	Q9ZRA2	-	670622
leaf	Cistus creticus	-	-	699799
leukocyte	Homo sapiens	-	-	697403
liver	Rattus norvegicus	-	-	439381, 439382
liver	Cavia porcellus, Oryctolagus cuniculus, Pigeon, Rattus norvegicus	-	higher activity than in kidney	439383
liver	Homo sapiens	-	-	439387
liver	Mus musculus	-	-	439388, 439390, 439393
liver	Bos taurus	-	-	439390, 712990
liver	Homo sapiens	-	embryonal liver	439390
liver	Oryctolagus cuniculus	-	-	439390
muscle	Mus musculus	-	expression of HGO gene	439388
mycelium	Phanerochaete chrysosporium	-	-	670853
pancreas	Mus musculus	-	expression of HGO gene	439388
placenta	Mus musculus	-	expression of HGO gene	439388
prostate gland	Homo sapiens	-	-	439387
root	Arabidopsis thaliana	Q9ZRA2	-	670622
small intestine	Homo sapiens	-	-	439387
spinal cord	Homo sapiens	-	-	712935
lung	Mus musculus	-	expression of HGO gene	439388
additional information	Cavia porcellus	-	not in heart	439383
additional information	Rattus norvegicus	-	not in cardiac and skeletal muscle, brain, spleen, intestine, pancreas, salivary gland, germinal epithelium, blood	439383
additional information	Bos taurus	B8YB76	tissue distribution of HGD, semi-quantitative RT-PCR analysis, overview	712990

LOCALIZATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	GeneOntology No.	LITERATURE	SOURCE
cytosol	Mus musculus	-	-	5829	439393
soluble	Bos taurus	-	-	-	396333

PDB	SCOP	CATH	ORGANISM
1ey2, download	SCOP (1ey2)	CATH (1ey2)	Homo sapiens
1eyb, download	SCOP (1eyb)	CATH (1eyb)	Homo sapiens

MOLECULAR WEIGHT	MOLECULAR WEIGHT MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
48000	-	Pseudomonas putida	-	SDS-PAGE	677068
52900	-	Phanerochaete chrysosporium	-	theoretical value	670853
149000	-	Mus musculus	-	gel filtration	439393
150000	-	Mus musculus	-	-	439392
199000	-	Arabidopsis thaliana	Q9ZRA2	gel filtration	670622
200000	-	Aspergillus niger	-	gel filtration	439386
254000	-	Bos taurus	-	-	439392
380000	-	Pseudomonas fluorescens	-	ultracentrifugal analysis	396333, 439380
424000	478000	Homo sapiens	-	equilibrium sedimentation studies	439392
450000	480000	Homo sapiens, Mus musculus, Oryctolagus cuniculus	-	sucrose density gradient centrifugation, can be degraded in two proteins of 200 and 230 kDa, probably due to inactivation by air	439390

SUBUNITS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
?	Mus musculus	-	x * 49000, SDS-PAGE	439388
?	Emericella nidulans	Q00667	x * 50168, calculated from the amino acid sequence	439391
hexamer	Homo sapiens	-	hexamer arranged as a dimer of trimers, subunit structure, functional importance of the hexamer in vivo	439392
hexamer	Homo sapiens	-	6 * 50150, mass spectrometry	657859
homohexamer	Homo sapiens	-	or dimer of trimer, X-ray crystallography	674157
monomer	Homo sapiens, Mus musculus, Oryctolagus cuniculus	-	1 * 450000-480000, SDS-PAGE	439390
tetramer	Arabidopsis thaliana	Q9ZRA2	4 * 49750, gel filtration	670622
trimer	Mus musculus	-	3 * 49000, SDS-PAGE	439393

POSTTRANSLATIONAL MODIFICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
no glycoprotein	Oryctolagus cuniculus	-	enzyme is not glycosylated	439390

Crystallization/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
crystal structures of apo-HGO and HGO containing an iron	Homo sapiens	-	439392
-	Pseudomonas fluorescens	-	396333, 439380

pH STABILITY	pH STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
6	7.2	Pseudomonas fluorescens	-	-20�C, stable for several weeks	439380

TEMPERATURE STABILITY	TEMPERATURE STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
25	55	Mus musculus	-	almost linear decrease of activity	439393
37	-	Homo sapiens	-	50% loss of activity after 17 s, pH 7.0; 50% loss of activity after 28 s, pH 6.2	657859
45	-	Mus musculus	-	65% loss of activity	439393

GENERAL STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
10% acetone stabilizes	Bos taurus	-	396333
rather stable enzyme, can be repeatedly thawed and frozen without significant loss of activity	Emericella nidulans	-	439389
ascorbate stabilizes, it probably protects Fe2+ from spontaneous oxidation	Mus musculus	-	439393
unlike the mammalian enzyme, the bacterial enzyme is fairly stable on aging or during storage	Pseudomonas fluorescens	-	396333, 439380

ORGANIC SOLVENT	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

OXIDATION STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
Fe2+, organic mercurials and reducing agents protect the enzyme from irreversible aerobic oxidation	Bos taurus	-	396333
inactivation by air probably causes degradation of enzyme in two proteins	Oryctolagus cuniculus	-	439390
sensitive to O2, easily inactivated by aeration	Pseudomonas fluorescens	-	439380

STORAGE STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
4�C, 20 mM Tris-Cl pH 7.8, 0.5 M NaCl, 0.3 M imidazole, 24 h, loses two third of its activity	Arabidopsis thaliana	Q9ZRA2	670622
-20�C, in absence of Fe2+, about 3 days, stable	Aspergillus niger	-	439386
-20�C, 50 mM potassium phosphate buffer, pH 7.0, crude extracts, 5 months, 25% loss of activity	Emericella nidulans	-	439389
-80, 20 mM Hepps, pH 8.0, 100 mM NaCl, 4 months, no loss of activity	Homo sapiens	-	657859
-20�C, pH 6.0-7.2, in absence of Fe2+, several weeks, stable	Pseudomonas fluorescens	-	439380

Purification/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
partial purification	Agave toumeyana, Agrostemma githago	-	439385
nickel chelate affinity chromatography	Arabidopsis thaliana	Q9ZRA2	670622
19.2fold purification	Aspergillus niger	-	439386
-	Bos taurus	-	439390
partial purification	Bos taurus	-	396333
partial purification	Daucus carota	-	439385
190fold purification	Drosophyllum lusitanicum	-	439385
purification of a fusion protein of homogentisate dioxygenase and glutathione S-transferase, expressed in Escherichia coli	Emericella nidulans	Q00667	439391
partial purification	Glycine max	-	439385
-	Homo sapiens	-	439390, 439392
recombinant His-tagged HGO, Ni-affinity, Mono Q	Homo sapiens	-	657859
partial purification	Melilotus albus	-	439385
-	Mus musculus	-	439388, 439390
330fold purification	Mus musculus	-	439393
partial purification	Nicotiana sylvestris	-	439385
54.1fold purification	Oryctolagus cuniculus	-	439390
partial purification	Phaseolus vulgaris, Pimpinella anisum	-	439385
-	Pseudomonas fluorescens	-	439380
Superdex gel filtration and Q-Sepharose column chromatography	Pseudomonas putida	-	677068
partial purification	Rattus norvegicus	-	439382
partial purification	Ruta graveolens, Solenostemon scutellarioides	-	439385

Cloned/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
expressed in Escherichia coli	Arabidopsis thaliana	Q9ZRA2	670622
DNA and amino acid sequence determination and analysis, genotyping, polymorphism of the HGD gene in the exon 1 and intron 1	Bos taurus	B8YB76	712929
gene HGD, DNA and amino acid sequence determination and analysis, genotyping, semi-quantitative RT-PCR analysis. Identification of nine single nucleotide polymorphisms, five in the coding region and four intronic	Bos taurus	B8YB76	712990
hmgA gene encoding homogentisate dioxygenase, a 448 residue polypeptide, is cloned, sequenced and characterized, gene is expressed in Escherichia coli as a fusion to glutathione S-transferase	Emericella nidulans	Q00667	439391
-	Exophiala lecanii-corni	Q6JDV6	657627
expression of His-tagged HGO in Escherichia coli	Homo sapiens	-	657859
genotyping	Homo sapiens	-	712909
HGO gene on chromosome 3 is cloned, completely sequenced and characterized, identification of its promoter region, transcriptional control of the gene	Homo sapiens	-	439387
PCR of coding region of DNA extracted from EDTA blood sample	Homo sapiens	-	697403
complete HGO cDNA, encoding for a 50 kDa protein, is cloned and sequenced	Mus musculus	-	439388

EXPRESSION	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

ENGINEERING	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
G161R	Homo sapiens	-	naturally occuring mutation in the HGD gene, resulting in a specific genotype appearing in a Hungarian population, originating from Slovakia, with alkaptonuria, phenotype overview	712909
G360R	Homo sapiens	-	active site mutation in exon 13	697403
additional information	Emericella nidulans	-	strain carrying an homogentisate dioxygenase gene disruption with full genotype biA1, methG1, deltahmgA without enzyme activity	439389
additional information	Emericella nidulans	Q00667	mutant strain biA1, methG1, argB2 with homogentisate dioxygenase gene disruption has no homogentisate dioxygenase activity and accumulates homogentisate	439391
K57N	Homo sapiens	-	active site mutation in exon 3	697403
additional information	Homo sapiens	-	alkaptonuric humans are deficient for homogentisate 1,2-dioxygenase and carry two copies of a loss-of-function allele of HGO gene	439387
additional information	Homo sapiens	-	human gene for alkaptonuria is mapped to chromosome 3q2	439390
additional information	Homo sapiens	-	20 missence mutations in HGO from alkaptonuria patients	439392
additional information	Mus musculus	-	alkaptonuric mouse lacks enzyme activity and have recessive mutation aku, mapped to chromosome 16, inbred strain C57BLG/J is heterozygous for the aku mutation	439390
additional information	Mus musculus	-	-	439392

Renatured/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

APPLICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
diagnostics	Emericella nidulans	-	crude enzyme preparations can be used for a spectrophotometric method for routine, sensitive determination of homogentisate in human urine	439389
medicine	Homo sapiens	-	alkaptonuria: rare hereditary disorder of the phenylalanine catabolism, patients are deficient in homogentisate 1,2-dioxygenase and carry two copies of a loss-of-function allele of HGO gene, disease causes homogentisic aciduria, ochronosis and arthritis	439387
medicine	Homo sapiens	-	inactivation of enzyme in kidney and liver causes the basic defect of alkaptonuria	439390
medicine	Homo sapiens	-	HGO deficiency causes alkaptonuria, inherited as a recessive Mendelian trait, HGO inhibitors may be useful in the treatment of hereditary tyrosinemia type I, HT1	439392
medicine	Homo sapiens	-	missense mutation in exon 13 (G360R) and exon 3 (K57N) affecting homogentisate 1,2-dioxygenase function by interfering with substrate traffic at active site causing alkaptonuria, a rare recessive phanylalanine/tyrosine metabolism disorder	697403
medicine	Mus musculus	-	HGO gene is responsible for alkaptonuria	439388
medicine	Mus musculus	-	-	439390, 439392

DISEASE	TITLE OF PUBLICATION	LINK TO PUBMED
Alkaptonuria	A late and difficult diagnosis of ochronosis.	PubMed
Alkaptonuria	A metabolic cause of spinal deformity.	PubMed
Alkaptonuria	A novel missense HGD gene mutation, K57N, in a patient with alkaptonuria.	PubMed
Alkaptonuria	A quantitative assessment of alkaptonuria : Testing the reliability of two disease severity scoring systems.	PubMed
Alkaptonuria	Alkaptonuria and intramedullary calcification.	PubMed
Alkaptonuria	Alkaptonuria and lumbar disc herniation. Report of three cases.	PubMed
Alkaptonuria	Alkaptonuria and ochronosis in three siblings. Ascorbic acid treatment monitored by urinary HGA excretion.	PubMed
Alkaptonuria	Alkaptonuria and ochronosis: case report and review.	PubMed
Alkaptonuria	Alkaptonuria and renal failure: a case report.	PubMed
Alkaptonuria	Alkaptonuria in France: past experience and lessons for the future.	PubMed
Alkaptonuria	Alkaptonuria in Italy: polymorphic haplotype background, mutational profile, and description of four novel mutations in the homogentisate 1,2-dioxygenase gene.	PubMed
Alkaptonuria	Alkaptonuria is a novel human secondary amyloidogenic disease.	PubMed
Alkaptonuria	Alkaptonuria presenting as lumbar disc prolapse: case report and review of literature.	PubMed
Alkaptonuria	Alkaptonuria, ochronosis, and ochronotic arthropathy.	PubMed
Alkaptonuria	Alkaptonuria--a review of surgical and autopsy pathology.	PubMed
Alkaptonuria	Alkaptonuria.	PubMed, PubMed
Alkaptonuria	Alkaptonuria: a case report.	PubMed
Alkaptonuria	Alkaptonuric ochronosis with aortic valve and joint replacements and femoral fracture: a case report and literature review.	PubMed
Alkaptonuria	Allelic heterogeneity of alkaptonuria in Central Europe.	PubMed
Alkaptonuria	Aortic stenosis in cardiovascular ochronosis.	PubMed
Alkaptonuria	Ashy ears.	PubMed
Alkaptonuria	Bilateral hip arthroplasty for ochronotic arthropathy.	PubMed
Alkaptonuria	Cementless total knee arthroplasty in ochronotic arthropathy: a case report with a 4-year follow-up.	PubMed
Alkaptonuria	Cloning of the homogentisate 1,2-dioxygenase gene, the key enzyme of alkaptonuria in mouse.	PubMed
Alkaptonuria	Devastating ochronotic arthropathy with successful bilateral hip and knee arthroplasties.	PubMed
Alkaptonuria	Early detection of alkaptonuria.	PubMed
Alkaptonuria	Early-onset ocular ochronosis in a girl with alkaptonuria (AKU) and a novel mutation in homogentisate 1,2-dioxygenase (HGD).	PubMed
Alkaptonuria	Endogenous ochronosis.	PubMed
Alkaptonuria	Evaluation of anti-oxidant treatments in an in vitro model of alkaptonuric ochronosis.	PubMed
Alkaptonuria	Evaluation of antioxidant drugs for the treatment of ochronotic alkaptonuria in an in vitro human cell model.	PubMed
Alkaptonuria	Exacerbation of the ochronosis of alkaptonuria due to renal insufficiency and improvement after renal transplantation.	PubMed
Alkaptonuria	From darkening urine to early diagnosis of alkaptonuria.	PubMed
Alkaptonuria	Fungal metabolic model for human type I hereditary tyrosinaemia.	PubMed
Alkaptonuria	Hemolysis in a Patient With Alkaptonuria and Chronic Kidney Failure.	PubMed
Alkaptonuria	Hereditary ochronosis: hyperpigmented skin overlying cartilaginous structures.	PubMed
Alkaptonuria	Hip arthroplasty for ochronosis.	PubMed
Alkaptonuria	Identification of the mutation in the alkaptonuria mouse model. Mutations in brief no. 216. Online.	PubMed
Alkaptonuria	Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain.	PubMed
Alkaptonuria	Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuria.	PubMed
Alkaptonuria	Natural history of alkaptonuria revisited: analyses based on scoring systems.	PubMed
Alkaptonuria	Natural history of alkaptonuria.	PubMed
Alkaptonuria	Neonatal severe primary hyperparathyroidism and alkaptonuria in a boy born to related parents with familial hypocalciuric hypercalcemia.	PubMed
Alkaptonuria	Nine cases of Alkaptonuria in one family in southern Jordan.	PubMed
Alkaptonuria	Nuclear medicine techniques in the assessment of alkaptonuria.	PubMed
Alkaptonuria	Ochronosis and lumbar disc herniation.	PubMed
Alkaptonuria	Ochronosis: a report of a case and a review of literature.	PubMed
Alkaptonuria	Ochronosis: report of two familial cases.	PubMed
Alkaptonuria	Ochronotic arthropathy: diagnosis and management: a critical review.	PubMed
Alkaptonuria	Ochronotic arthropathy: disappearance of alkaptonuria after liver transplantation for hepatitis B-related cirrhosis.	PubMed
Alkaptonuria	Ochronotic rheumatism in Algeria: clinical, radiological, biological and molecular studies--a case study of 14 patients in 11 families.	PubMed
Alkaptonuria	Ocular ochronosis from alkaptonuria.	PubMed
Alkaptonuria	Ocular ochronosis in alkaptonuria patients carrying mutations in the homogentisate 1,2-dioxygenase gene.	PubMed
Alkaptonuria	Osteoarthritis? Ochronotic arthritis! : A case study and review of the literature.	PubMed
Alkaptonuria	Redox-proteomics of the effects of homogentisic acid in an in vitro human serum model of alkaptonuric ochronosis.	PubMed
Alkaptonuria	Shoulder arthroplasty in alkaptonuric arthropathy: a clinical case report and literature review.	PubMed
Alkaptonuria	Three-generational alkaptonuria in a non-consanguineous family.	PubMed
Alkaptonuria	Unrecognized ochronosis--a case report.	PubMed
Alkaptonuria	[A child with dark discoloration of urine]	PubMed
Alkaptonuria	[Alkaptonuria: a rare cause of urine discoloration. Report of a case in a newborn]	PubMed
Alkaptonuria	[Alkaptonuria: a rare metabolic disorder. A report of two cases in siblings]	PubMed
Alkaptonuria	[Case report of a patient with ochronosis and arthroplasty of the hip and both knees]	PubMed
Alkaptonuria	[Endogenous ochronosis: a case description]	PubMed
Alkaptonuria	[Important bilateral corneal astigmatism in a case of ocular ochronosis]	PubMed
Alkaptonuria	[Knee ochronotic arthropathy and arthroscopic findings]	PubMed
Alkaptonuria	[Ochronotic arthropathy in alkaptonuria. Radiological manifestations and physiopathological signs]	PubMed
Alkaptonuria	[Ochronotic changes in alkaptonuria: a case report]	PubMed
Aortic Valve Stenosis	Aortic stenosis in endogenous ochronosis.	PubMed
Arthritis	Alkaptonuria and intramedullary calcification.	PubMed
Arthritis	Molecular analyses of the HGO gene mutations in Turkish alkaptonuria patients suggest that the R58fs mutation originated from central Asia and was spread throughout Europe and Anatolia by human migrations.	PubMed
Back Pain	A metabolic cause of spinal deformity.	PubMed
Genetic Diseases, Inborn	Alkaptonuria.	PubMed
Genetic Diseases, Inborn	[Alkaptonuria: a rare cause of urine discoloration. Report of a case in a newborn]	PubMed
homogentisate 1,2-dioxygenase deficiency	Exacerbation of the ochronosis of alkaptonuria due to renal insufficiency and improvement after renal transplantation.	PubMed
homogentisate 1,2-dioxygenase deficiency	Natural history of alkaptonuria.	PubMed
homogentisate 1,2-dioxygenase deficiency	[Alkaptonuria: a rare metabolic disorder. A report of two cases in siblings]	PubMed
homogentisate 1,2-dioxygenase deficiency	[Knee ochronotic arthropathy and arthroscopic findings]	PubMed
homogentisate 1,2-dioxygenase deficiency	[Ochronotic changes in alkaptonuria: a case report]	PubMed
Joint Diseases	Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain.	PubMed
Metabolic Diseases	Alkaptonuria and lumbar disc herniation. Report of three cases.	PubMed
Metabolic Diseases	Fungal metabolic model for human type I hereditary tyrosinaemia.	PubMed
Metabolic Diseases	Shoulder arthroplasty in alkaptonuric arthropathy: a clinical case report and literature review.	PubMed
Metabolic Diseases	[A child with dark discoloration of urine]	PubMed
Metabolic Diseases	[Arthroplasty for the treatment of joint degeneration caused by ochronosis in two cases.]	PubMed
Metabolic Diseases	[Important bilateral corneal astigmatism in a case of ocular ochronosis]	PubMed
Metabolic Diseases	[Knee ochronotic arthropathy and arthroscopic findings]	PubMed
Metabolic Diseases	[Ochronotic arthropathy in alkaptonuria. Radiological manifestations and physiopathological signs]	PubMed
Neoplasms	D-Aminoacid oxidase and homogentisate oxygenase activities in the tumor bearing rats.	PubMed
Osteoarthritis	Ochronosis: a report of a case and a review of literature.	PubMed
Tyrosinemias	Tissue distribution of 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1-3-dione (NTBC): effect on enzymes involved in tyrosine catabolism and relevance to ocular toxicity in the rat.	PubMed

REF.	AUTHORS	TITLE	JOURNAL	VOL.	PAGES	YEAR	ORGANISM	LINK TO PUBMED	SOURCE
396333	Nozaki, M.	Nonheme iron dioxygenase	Mol. Mech. Oxygen Activ. (Hayaishi, O., ed.) Academic Press, New York		135-165	1974	Bos taurus, Pseudomonas fluorescens	-
439380	Adachi, K.; Iwayama, Y.; Tanioka, H.; Takeda, Y.	Purification and properties of homogentisate oxygenase from Pseudomonas fluorescens	Biochim. Biophys. Acta	118	88-97	1966	Pseudomonas fluorescens	PubMed
439381	Ravdin, R.G.; Crandall, D.I.	The enzymatic conversion of homogentisic acid to 4-fumarylacetoacetic acid	J. Biol. Chem.	189	137-149	1951	Rattus norvegicus	PubMed
439382	Knox, W.E.; Edwards, S.W.	Homogentisate oxidase of liver	J. Biol. Chem.	216	479-487	1955	Rattus norvegicus	PubMed
439383	Crandall, D.I.; Halikis, D.N.	Homogentisic acid oxidase. I. Distribution in animal tissues and relation to tyrosine metabolism in rat kidney	J. Biol. Chem.	208	629-638	1954	Cavia porcellus, Oryctolagus cuniculus, Pigeon, Rattus norvegicus	PubMed
439385	Durand, R.; Zenk, M.H.	Enzymes of the homogentisate ring-cleavage pathway in cell suspension cultures of higher plants	FEBS Lett.	39	218-220	1974	Agave toumeyana, Agrostemma githago, Daucus carota, Drosophyllum lusitanicum, Glycine max, Melilotus albus, Nicotiana sylvestris, Phaseolus vulgaris, Pimpinella anisum, Ruta graveolens, Solenostemon scutellarioides	PubMed
439386	Sugumaran, M.; Vaidyanathan, C.S.	Affinity chromatography of homogentisate-1,2-dioxygenase from Aspergillus niger	FEMS Microbiol. Lett.	4	343-347	1978	Aspergillus niger	-
439387	Granadino, B.; Beltran-Valero de Bernabe, D.; Fernandez-Canon, J.M.; Penalva, M.A.; Rodriguez de Cordoba, S.	The human homogentisate 1,2-dioxygenase (HGO) gene	Genomics	43	115-122	1997	Homo sapiens	PubMed
439388	Schmidt, S.R.; Gehrig, A.; Koehler, M.R.; Schmid, M.; Muller, C.R.; Kress, W.	Cloning of the homogentisate 1,2-dioxygenase gene, the key enzyme of alkaptonuria in mouse	Mamm. Genome	8	168-171	1997	Mus musculus	PubMed
439389	Fernandez-Canon, J.M.; Penalva, M.A.	Spectrophotometric determination of homogentisate using Aspergillus nidulans homogentisate dioxygenase	Anal. Biochem.	245	218-221	1997	Emericella nidulans	PubMed
439390	Hudecova, S.; Strakova, Z.; Krizanova, O.	Purification of the homogentisic acid oxidase from mammalian liver	Int. J. Biochem. Cell Biol.	27	1357-1363	1995	Bos taurus, Homo sapiens, Mus musculus, Oryctolagus cuniculus	PubMed
439391	Fernandez-Canon, J.M.; Penalva, M.A.	Molecular characterization of a gene encoding a homogentisate dioxygenase from Aspergillus nidulans and identification of its human and plant homologues	J. Biol. Chem.	270	21199-21205	1995	Emericella nidulans	PubMed
439392	Titus, G.P.; Mueller, H.A.; Burgner, J.; Rodriguez de Cordoba, S.; Penalva, M.A.; Timm, D.E.	Crystal structure of human homogentisate dioxygenase	Nat. Struct. Biol.	7	542-546	2000	Bos taurus, Homo sapiens, Mus musculus	PubMed
439393	Schmidt, S.R.; Muller, C.R.; Kress, W.	Murine liver homogentisate 1,2-dioxygenase. Purification to homogeneity and novel biochemical properties	Eur. J. Biochem.	228	425-430	1995	Mus musculus	PubMed
657627	Gunsch, C.K.; Cheng, Q.; Kinney, K.A.; Szaniszlo, P.J.; Whitman, C.P.	Identification of a homogentisate-1,2-dioxygenase gene in the fungus Exophiala lecanii-corni: analysis and implications	Appl. Microbiol. Biotechnol.	68	405-411	2005	Exophiala lecanii-corni	PubMed
657859	Veldhuizen, E.J.; Vaillancourt, F.H.; Whiting, C.J.; Hsiao, M.M.; Gingras, G.; Xiao, Y.; Tanguay, R.M.; Boukouvalas, J.; Eltis, L.D.	Steady-state kinetics and inhibition of anaerobically purified human homogentisate 1,2-dioxygenase	Biochem. J.	386	305-314	2005	Homo sapiens	PubMed
670622	Dixon, D.P.; Edwards, R.	Enzymes of tyrosine catabolism in Arabidopsis thaliana	Plant Sci.	171	360-366	2006	Arabidopsis thaliana	PubMed
670853	Shimizu, M.; Yuda, N.; Nakamura, T.; Tanaka, H.; Wariishi, H.	Metabolic regulation at the tricarboxylic acid and glyoxylate cycles of the lignin-degrading basidiomycete Phanerochaete chrysosporium against exogenous addition of vanillin	Proteomics	5	3919-3931	2005	Phanerochaete chrysosporium	PubMed
674157	Borowski, T.; Georgiev, V.; Siegbahn, P.E.	Catalytic reaction mechanism of homogentisate dioxygenase: a hybrid DFT study	J. Am. Chem. Soc.	127	17303-17314	2005	Homo sapiens	PubMed
677068	Kim, Y.H.; Cho, K.; Yun, S.H.; Kim, J.Y.; Kwon, K.H.; Yoo, J.S.; Kim, S.I.	Analysis of aromatic catabolic pathways in Pseudomonas putida KT 2440 using a combined proteomic approach: 2-DE/MS and cleavable isotope-coded affinity tag analysis	Proteomics	6	1301-1318	2006	Pseudomonas putida	PubMed
686266	Kang, B.R.; Han, S.H.; Cho, S.M.; Anderson, A.J.; Kim, I.S.; Park, S.K.; Kim, Y.C.	Characterization of a homogentisate dioxygenase mutant in Pseudomonas chlororaphis O6	Curr. Microbiol.	56	145-149	2008	Pseudomonas chlororaphis	PubMed
686387	Yoon, S.S.; Karabulut, A.C.; Lipscomb, J.D.; Hennigan, R.F.; Lymar, S.V.; Groce, S.L.; Herr, A.B.; Howell, M.L.; Kiley, P.J.; Schurr, M.J.; Gaston, B.; Choi, K.H.; Schweizer, H.P.; Hassett, D.J.	Two-pronged survival strategy for the major cystic fibrosis pathogen, Pseudomonas aeruginosa, lacking the capacity to degrade nitric oxide during anaerobic respiration	EMBO J.	26	3662-3672	2007	Pseudomonas aeruginosa	PubMed
686802	Zhang, Y.; Wang, L.; Zhang, S.; Yang, H.; Tan, H.	hmgA, transcriptionally activated by HpdA, influences the biosynthesis of actinorhodin in Streptomyces coelicolor	FEMS Microbiol. Lett.	280	219-225	2008	Streptomyces coelicolor	PubMed
697403	Grasko, J.M.; Hooper, A.J.; Brown, J.W.; McKnight, C.J.; Burnett, J.R.	A novel missense HGD gene mutation, K57N, in a patient with alkaptonuria	Clin. Chim. Acta	403	254-256	2009	Homo sapiens	PubMed
699799	Munne-Bosch, S.; Falara, V.; Pateraki, I.; Lopez-Carbonell, M.; Cela, J.; Kanellis, A.K.	Physiological and molecular responses of the isoprenoid biosynthetic pathway in a drought-resistant Mediterranean shrub, Cistus creticus exposed to water deficit	J. Plant Physiol.	166	136-145	2009	Cistus creticus	PubMed
706809	Battilana, J.; Costantini, L.; Emanuelli, F.; Sevini, F.; Segala, C.; Moser, S.; Velasco, R.; Versini, G.; Stella Grando, M.	The 1-deoxy-D: -xylulose 5-phosphate synthase gene co-localizes with a major QTL affecting monoterpene content in grapevine	Theor. Appl. Genet.	118	653-669	2009	Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera	PubMed
712561	Tinti, L.; Spreafico, A.; Braconi, D.; Millucci, L.; Bernardini, G.; Chellini, F.; Cavallo, G.; Selvi, E.; Galeazzi, M.; Marcolongo, R.; Gallagher, J.A.; Santucci, A.	Evaluation of antioxidant drugs for the treatment of ochronotic alkaptonuria in an in vitro human cell model	J. Cell. Physiol.	225	84-91	2010	Homo sapiens	PubMed
712909	Toth, K.; Kiss-Laaszlo, Z.; Lenart, E.; Juhasz, K.; Takacs, K.; Bender, T.; Szabo, J.	Familiar ochronotic arthropathy-caused by a gene mutation traced three hundred years	Joint Bone Spine	77	355-357	2010	Homo sapiens	PubMed
712929	Zhou, G.L.; Cao, Y.; Li, M.; Zhang, L.C.; Yu, Y.S.; Jin, H.G.	Meat quality and carcass traits in relation to HGD-BstXI and HGD-HaeIII PCR-RFLP polymorphism in Chinese red cattle	Meat Sci.	85	270-273	2010	Bos taurus	PubMed
712935	Effelsberg, N.; Huegle, T.; Walker, U.	A metabolic cause of spinal deformity	Metab. Clin. Exp.	59	140-143	2010	Homo sapiens	PubMed
712990	Zhou, G.; Dudgeon, C.; Li, M.; Cao, Y.; Zhang, L.; Jin, H.	Molecular cloning of the HGD gene and association of SNPs with meat quality traits in Chinese red cattle	Mol. Biol. Rep.	37	603-611	2010	Bos taurus	PubMed

LINKS TO OTHER DATABASES (specific for EC-Number 1.13.11.5)

NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM

IUBMB Enzyme Nomenclature

PROSITE Database of protein families and domains

SYSTERS

Protein Mutant Database

InterPro (database of protein families, domains and functional sites)

All organisms
Agave toumeyana
Agrostemma githago
Arabidopsis thaliana
Aspergillus niger
Bos taurus
Bos taurus Chinese red cattle
Cavia porcellus
Cistus creticus
Daucus carota
Drosophyllum lusitanicum
Emericella nidulans
Emericella nidulans BiA1
Exophiala lecanii-corni
Glycine max
Homo sapiens
Melilotus albus
Mus musculus
Nicotiana sylvestris
Oryctolagus cuniculus
Phanerochaete chrysosporium
Phaseolus vulgaris
Pigeon
Pimpinella anisum
Pseudomonas aeruginosa
Pseudomonas chlororaphis
Pseudomonas fluorescens
Pseudomonas putida
Rattus norvegicus
Ruta graveolens
Solenostemon scutellarioides
Streptomyces coelicolor
Vitis vinifera x Vitis riparia
Vitis vinifera x Vitis vinifera