1EY2

HUMAN HOMOGENTISATE DIOXYGENASE WITH FE(II)

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Structure Motif: Primary M-CSA Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1ey2a_	All beta proteins	Double-stranded beta-helix	RmlC-like cupins	Homogentisate dioxygenase	Homogentisate dioxygenase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	RmlC-like cupins	8043044	3001825	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF04209	e1ey2A2	A: beta sandwiches	X: jelly-roll	H: Double-stranded beta-helix (From Topology)	T: Double-stranded beta-helix	F: PF04209	ECOD (1.6)
A	PF20510	e1ey2A3	A: beta sandwiches	X: jelly-roll	H: Double-stranded beta-helix (From Topology)	T: Double-stranded beta-helix	F: PF20510	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.60.120.10	Mainly Beta	Sandwich	Jelly Rolls	Jelly Rolls	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF04209	Homogentisate 1,2-dioxygenase C-terminal (HgmA_C)	Homogentisate 1,2-dioxygenase C-terminal	Homogentisate dioxygenase cleaves the aromatic ring during the metabolic degradation of Phe and Tyr. Homogentisate dioxygenase deficiency causes alkaptonuria. The structure of homogentisate dioxygenase shows that the enzyme forms a hexamer arrangem ...	Homogentisate dioxygenase cleaves the aromatic ring during the metabolic degradation of Phe and Tyr. Homogentisate dioxygenase deficiency causes alkaptonuria. The structure of homogentisate dioxygenase shows that the enzyme forms a hexamer arrangement comprised of a dimer of trimers. The active site iron ion is coordinated near the interface between the trimers [1]. This entry represents the C-terminal active site domain.	Domain
A	PF20510	Homogentisate 1,2-dioxygenase N-terminal (HgmA_N)	Homogentisate 1,2-dioxygenase N-terminal	Homogentisate dioxygenase cleaves the aromatic ring during the metabolic degradation of Phe and Tyr. Homogentisate dioxygenase deficiency causes alkaptonuria. The structure of homogentisate dioxygenase shows that the enzyme forms a hexamer arrangem ...	Homogentisate dioxygenase cleaves the aromatic ring during the metabolic degradation of Phe and Tyr. Homogentisate dioxygenase deficiency causes alkaptonuria. The structure of homogentisate dioxygenase shows that the enzyme forms a hexamer arrangement comprised of a dimer of trimers. The active site iron ion is coordinated near the interface between the trimers [1]. This entry represents the N-terminal domain which forms a jelly roll of beta-strands [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	HOMOGENTISATE 1,2-DIOXYGENASE	homogentisate 1,2-dioxygenase activity oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen oxidoreductase activity oxidoreductase activity, acting on single donors with incorporation of molecular oxygen catalytic activity dioxygenase activity cation binding ion binding binding metal ion binding small molecule binding identical protein binding protein binding	catabolic process oxoacid metabolic process aromatic amino acid family catabolic process amino acid metabolic process organic acid catabolic process organic acid metabolic process alpha-amino acid metabolic process cellular catabolic process organic substance metabolic process carboxylic acid catabolic process small molecule metabolic process amino acid catabolic process organonitrogen compound catabolic process erythrose 4-phosphate/phosphoenolpyruvate family amino acid metabolic process catabolic process oxoacid metabolic process aromatic amino acid family catabolic process amino acid metabolic process organic acid catabolic process organic acid metabolic process alpha-amino acid metabolic process cellular catabolic process organic substance metabolic process carboxylic acid catabolic process small molecule metabolic process amino acid catabolic process organonitrogen compound catabolic process erythrose 4-phosphate/phosphoenolpyruvate family amino acid metabolic process organonitrogen compound metabolic process L-phenylalanine catabolic process aromatic amino acid metabolic process cellular metabolic process carboxylic acid metabolic process L-amino acid catabolic process primary metabolic process organic cyclic compound catabolic process L-amino acid metabolic process L-phenylalanine metabolic process organic cyclic compound metabolic process proteinogenic amino acid metabolic process erythrose 4-phosphate/phosphoenolpyruvate family amino acid catabolic process alpha-amino acid catabolic process proteinogenic amino acid catabolic process metabolic process cellular process small molecule catabolic process organic substance catabolic process tyrosine metabolic process tyrosine catabolic process	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR046452	Homogentisate 1,2-dioxygenase, N-terminal domain	Domain
A	IPR011051	RmlC-like cupin domain superfamily	Homologous Superfamily
A	IPR046451	Homogentisate 1,2-dioxygenase, C-terminal domain	Domain
A	IPR005708	Homogentisate 1,2-dioxygenase	Family
A	IPR014710	RmlC-like jelly roll fold	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q93099	alkaptonuria pancreatic intraductal papillary-mucinous carcinoma rhinitis chronic obstructive pulmonary disease endometriosis gastric carcinoma lung adenocarcinoma nephrosclerosis osteosarcoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia subependymal giant cell astrocytoma asthma Crohn disease exocrine pancreatic carcinoma head and neck cancer alkaptonuria pancreatic intraductal papillary-mucinous carcinoma rhinitis chronic obstructive pulmonary disease endometriosis gastric carcinoma lung adenocarcinoma nephrosclerosis osteosarcoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia subependymal giant cell astrocytoma asthma Crohn disease exocrine pancreatic carcinoma head and neck cancer lung carcinoma non-small cell lung carcinoma pancreatic ductal adenocarcinoma psoriasis ulcerative colitis breast fibroadenoma ductal breast carcinoma in situ gastric cancer inborn errors of metabolism malignant pancreatic neoplasm ochronosis disorder

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	homogentisate 1,2-dioxygenase M-CSA #547	Homogentistate dioxygenase (HGO) catalyses the metabolic degredation of Phe and Tyr amino acids. The ring opening reaction requires non-heme Fe(2+) to incorporate both atoms of molecular oxygen into homogentisate. The accumulation of this substrate, when insufficient levels of HGO are present, results in the deposition of of insoluble ochromotic pigments in conective tissues, leading to degenerative arthritis.	Defined by 5 residues: HIS:A-318 [auth A-292]HIS:A-361 [auth A-335]GLU:A-367 [auth A-341]HIS:A-391 [auth A-365]HIS:A-397 [auth A-371] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 1.13.11.5 (PDB Primary Data) Search M-CSA Motif + EC 1.13.11.5

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.