6ZVP | pdb_00006zvp

Atomic model of the EM-based structure of the full-length tyrosine hydroxylase in complex with dopamine (residues 40-497) in which the regulatory domain (residues 40-165) has been included only with the backbone atoms

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A [auth D]	SCOP2B Superfamily	Aromatic aminoacid monoxygenases, catalytic and oligomerization domains	8069027	3001457	SCOP2B (2022-06-29)
B [auth A]	SCOP2B Superfamily	Aromatic aminoacid monoxygenases, catalytic and oligomerization domains	8069027	3001457	SCOP2B (2022-06-29)
C [auth B]	SCOP2B Superfamily	Aromatic aminoacid monoxygenases, catalytic and oligomerization domains	8069027	3001457	SCOP2B (2022-06-29)
D [auth C]	SCOP2B Superfamily	Aromatic aminoacid monoxygenases, catalytic and oligomerization domains	8069027	3001457	SCOP2B (2022-06-29)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A [auth D]	1.10.800.10	Mainly Alpha	Orthogonal Bundle	Phenylalanine Hydroxylase	Aromatic amino acid hydroxylase	CATH (utative)
B [auth A]	1.10.800.10	Mainly Alpha	Orthogonal Bundle	Phenylalanine Hydroxylase	Aromatic amino acid hydroxylase	CATH (utative)
C [auth B]	1.10.800.10	Mainly Alpha	Orthogonal Bundle	Phenylalanine Hydroxylase	Aromatic amino acid hydroxylase	CATH (utative)
D [auth C]	1.10.800.10	Mainly Alpha	Orthogonal Bundle	Phenylalanine Hydroxylase	Aromatic amino acid hydroxylase	CATH (utative)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth D], B [auth A], C [auth B], D [auth C]	PF21417	Tyrosine 3-monooxygenase-like, ACT domain (TH_ACT)	Tyrosine 3-monooxygenase-like, ACT domain	This domain is found in Tyrosine 3-monooxygenase from Rattus norvegicus (TH) and similar proteins from vertebrates. TH catalyses the hydroxylation of tyrosine to form 3,4-dihydroxyphenylalanine in the biosynthesis of the catecholamine neurotransmitte ...	This domain is found in Tyrosine 3-monooxygenase from Rattus norvegicus (TH) and similar proteins from vertebrates. TH catalyses the hydroxylation of tyrosine to form 3,4-dihydroxyphenylalanine in the biosynthesis of the catecholamine neurotransmitters. This entry represents the regulatory domain, which is centrally located (C- terminal to Pfam:PF12549 and N-terminal to Pfam:PF00351). It is an ACT domain that shows a four stranded antiparallel beta-sheet and two alpha-helices connected by four loops. It adopts a dimeric configuration [1-3]. In humans, TH is associated with several disorders [4].	Domain
A [auth D], B [auth A], C [auth B], D [auth C]	PF00351	Biopterin-dependent aromatic amino acid hydroxylase (Biopterin_H)	Biopterin-dependent aromatic amino acid hydroxylase	This family includes phenylalanine-4-hydroxylase, the phenylketonuria disease protein.	Domain
A [auth D], B [auth A], C [auth B], D [auth C]	PF12549	Tyrosine hydroxylase N terminal (TOH_N)	Tyrosine hydroxylase N terminal	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth D], B [auth A], C [auth B], D [auth C]	Tyrosine 3-monooxygenase	cation binding transition metal ion binding iron ion binding ion binding binding ferrous iron binding metal ion binding small molecule binding amino acid binding catecholamine binding dopamine binding identical protein binding protein binding protein domain specific binding cation binding transition metal ion binding iron ion binding ion binding binding ferrous iron binding metal ion binding small molecule binding amino acid binding catecholamine binding dopamine binding identical protein binding protein binding protein domain specific binding ferric iron binding tetrahydrobiopterin binding oxygen binding oxidoreductase activity monooxygenase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen tyrosine 3-monooxygenase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen catalytic activity enzyme binding	heart process multicellular organismal process system process regulation of biological process regulation of heart contraction regulation of system process biological regulation circulatory system process regulation of blood circulation regulation of multicellular organismal process heart contraction blood circulation developmental process heart development heart process multicellular organismal process system process regulation of biological process regulation of heart contraction regulation of system process biological regulation circulatory system process regulation of blood circulation regulation of multicellular organismal process heart contraction blood circulation developmental process heart development multicellular organism development anatomical structure development animal organ development circulatory system development system development behavior learning learning or memory nervous system process cognition epinephrine biosynthetic process catechol-containing compound metabolic process amine metabolic process biogenic amine biosynthetic process biosynthetic process epinephrine metabolic process catecholamine metabolic process amine biosynthetic process phenol-containing compound metabolic process catecholamine biosynthetic process phenol-containing compound biosynthetic process metabolic process cellular process catechol-containing compound biosynthetic process biogenic amine metabolic process reproductive process multicellular organismal reproductive process reproductive behavior mating behavior oxoacid metabolic process dopamine metabolic process amino acid metabolic process organic acid metabolic process alpha-amino acid metabolic process dopamine biosynthetic process small molecule metabolic process tyrosine metabolic process dopamine biosynthetic process from tyrosine erythrose 4-phosphate/phosphoenolpyruvate family amino acid metabolic process aromatic amino acid metabolic process carboxylic acid metabolic process primary metabolic process L-amino acid metabolic process proteinogenic amino acid metabolic process response to light stimulus response to stimulus response to radiation response to abiotic stimulus memory norepinephrine biosynthetic process norepinephrine metabolic process cellular response to nitrogen compound cellular response to stimulus cellular response to chemical stimulus response to chemical response to nitrogen compound cellular response to alkaloid response to alkaloid heart morphogenesis anatomical structure morphogenesis animal organ morphogenesis response to ketone response to lipid response to endogenous stimulus response to alcohol response to glucocorticoid response to oxygen-containing compound response to corticosterone response to mineralocorticoid response to corticosteroid response to hormone response to steroid hormone response to electrical stimulus response to metal ion response to zinc ion membrane lipid metabolic process sphingolipid metabolic process lipid metabolic process head development forebrain development brain development nervous system development pallium development cerebral cortex development central nervous system development telencephalon development trans-synaptic signaling signaling cell-cell signaling chemical synaptic transmission cell communication synaptic signaling anterograde trans-synaptic signaling synaptic transmission, dopaminergic response to decreased oxygen levels response to hypoxia response to stress response to oxygen levels cellular localization nitrogen compound transport transport synaptic vesicle cycle neurotransmitter transport establishment of localization vesicle-mediated transport vesicle-mediated transport in synapse amine transport localization aminergic neurotransmitter loading into synaptic vesicle neurotransmitter loading into synaptic vesicle establishment of localization in cell sensory organ development embryonic eye morphogenesis visual system development embryo development embryonic camera-type eye development eye morphogenesis embryonic organ development sensory system development embryonic organ morphogenesis camera-type eye morphogenesis eye development embryonic morphogenesis embryonic camera-type eye morphogenesis sensory organ morphogenesis camera-type eye development cellular response to xenobiotic stimulus response to xenobiotic stimulus pigmentation response to nutrient levels alkaloid metabolic process isoquinoline alkaloid metabolic process response to osmotic stress response to salt stress phytoalexin metabolic process toxin metabolic process secondary metabolic process response to ether locomotory behavior response to peptide hormone glycosyl compound metabolic process glycoside metabolic process carbohydrate derivative metabolic process terpene metabolic process hydrocarbon metabolic process isoprenoid metabolic process phthalate metabolic process benzene-containing compound metabolic process homeostatic process cellular response to glucose stimulus intracellular glucose homeostasis cellular response to oxygen-containing compound response to hexose cellular response to carbohydrate stimulus cellular homeostasis response to monosaccharide response to carbohydrate chemical homeostasis response to glucose glucose homeostasis carbohydrate homeostasis cellular response to hexose stimulus intracellular chemical homeostasis cellular response to monosaccharide stimulus anatomical structure regression hyaloid vascular plexus regression response to activity eating behavior feeding behavior cellular developmental process photoreceptor cell differentiation cell development neurogenesis neuron differentiation cell differentiation eye photoreceptor cell differentiation photoreceptor cell development eye photoreceptor cell development generation of neurons neuron development rhythmic process circadian sleep/wake cycle circadian behavior rhythmic behavior circadian rhythm cellular response to metal ion cellular response to manganese ion response to manganese ion response to ethanol fatty acid metabolic process monocarboxylic acid metabolic process cellular response to nicotine response to nicotine cellular response to endogenous stimulus cellular response to growth factor stimulus response to growth factor response to immobilization stress response to herbicide response to toxic substance response to isolation stress biological process involved in intraspecies interaction between organisms social behavior sensory perception of light stimulus sensory perception visual perception response to amine response to amphetamine biological process involved in interspecies interaction between organisms response to other organism response to external stimulus response to lipopolysaccharide response to biotic stimulus response to bacterium response to external biotic stimulus response to molecule of bacterial origin response to pyrethroid response to insecticide response to estradiol	somatodendritic compartment cell body cellular anatomical structure perikaryon neuronal cell body intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle organelle endoplasmic reticulum smooth endoplasmic reticulum intracellular membrane-bounded organelle somatodendritic compartment cell body cellular anatomical structure perikaryon neuronal cell body intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle organelle endoplasmic reticulum smooth endoplasmic reticulum intracellular membrane-bounded organelle endomembrane system cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection perinuclear region of cytoplasm axon transport vesicle synapse intracellular vesicle presynapse cytoplasmic vesicle synaptic vesicle cell junction secretory vesicle vesicle exocytic vesicle pigment granule membrane chitosome melanosome cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane melanosome membrane organelle membrane pigment granule membrane mitochondrion axon terminus distal axon terminal bouton neuron projection terminus cell periphery cytoplasmic side of plasma membrane cytoplasmic side of membrane plasma membrane side of membrane nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth D], B [auth A], C [auth B], D [auth C]	IPR005962	Tyrosine 3-monooxygenase	Family
A [auth D], B [auth A], C [auth B], D [auth C]	IPR021164	Tyrosine hydroxylase, conserved site	Conserved Site
A [auth D], B [auth A], C [auth B], D [auth C]	IPR019773	Tyrosine 3-monooxygenase-like	Family
A [auth D], B [auth A], C [auth B], D [auth C]	IPR049321	Tyrosine 3-monooxygenase-like, ACT domain	Domain
A [auth D], B [auth A], C [auth B], D [auth C]	IPR019774	Aromatic amino acid hydroxylase, C-terminal	Domain
A [auth D], B [auth A], C [auth B], D [auth C]	IPR036329	Aromatic amino acid monoxygenase, C-terminal domain superfamily	Homologous Superfamily
A [auth D], B [auth A], C [auth B], D [auth C]	IPR036951	Aromatic amino acid hydroxylase superfamily	Homologous Superfamily
A [auth D], B [auth A], C [auth B], D [auth C]	IPR045865	ACT-like domain	Homologous Superfamily
A [auth D], B [auth A], C [auth B], D [auth C]	IPR041903	Tyrosine 3-monooxygenase, catalytic domain	Domain
A [auth D], B [auth A], C [auth B], D [auth C]	IPR001273	Aromatic amino acid hydroxylase	Family
A [auth D], B [auth A], C [auth B], D [auth C]	IPR018301	Aromatic amino acid hydroxylase, iron/copper binding site	Binding Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth D], B [auth A], C [auth B], D [auth C]	Pharos: P07101	Catalepsy dystonic disorder intellectual disability TH-deficient dopa-responsive dystonia neuroblastoma hypertensive disorder Parkinson disease phaeochromocytoma heart disease brain disease toxic encephalopathy adenoma adrenal gland pheochromocytoma depressive disorder prostate carcinoma Catalepsy dystonic disorder intellectual disability TH-deficient dopa-responsive dystonia neuroblastoma hypertensive disorder Parkinson disease phaeochromocytoma heart disease brain disease toxic encephalopathy adenoma adrenal gland pheochromocytoma depressive disorder prostate carcinoma type 1 diabetes mellitus adrenal cortex adenoma learning disability bipolar disorder cervical cancer parkinsonian disorder extra-adrenal sympathetic paraganglioma hepatocellular carcinoma adrenal cortex carcinoma interstitial cystitis autosomal recessive juvenile Parkinson disease 2 major depressive disorder delirium drug-induced dyskinesia

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), 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 R01GM157729.