TH encodes tyrosine 3-monooxygenase (tyrosine hydroxylase; EC 1.14.16.2), the rate-limiting enzyme of catecholamine biosynthesis. It catalyzes the hydroxylation of L-tyrosine to L-DOPA (L-3,4-dihydroxyphenylalanine), the first and committed step in the synthesis of the catecholamines dopamine, noradrenaline (norepinephrine) and adrenaline (epinephrine). The reaction uses the cofactor (6R)-tetrahydrobiopterin (BH4), molecular oxygen, and a non-heme ferrous iron [Fe(II)] center; the enzyme is a member of the biopterin-dependent aromatic amino acid hydroxylase family and can also hydroxylate phenylalanine and tryptophan with lower specificity. TH is a homotetramer with an N-terminal regulatory domain and a C-terminal catalytic domain. It is a predominantly cytosolic enzyme of catecholaminergic neurons (substantia nigra, ventral tegmental area, locus coeruleus) and adrenal chromaffin cells, and also localizes to axons and secretory/synaptic vesicles. Its activity is tightly controlled by end-product feedback inhibition (catecholamines competing with BH4) and by phosphorylation of N-terminal serine residues (Ser19, Ser40, Ser62, Ser71) by kinases such as PKA and CaMKII, which relieves feedback inhibition and regulates enzyme stability and 14-3-3 (YWHAG) binding. Loss-of-function variants cause autosomal-recessive DOPA-responsive dystonia / infantile parkinsonism-dystonia (Segawa syndrome, tyrosine hydroxylase deficiency).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004511 tyrosine 3-monooxygenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) transfer of the defining catalytic activity of TH. This is the correct core molecular function and is supported by extensive experimental evidence in this same gene. Supporting Evidence: file:human/TH/TH-uniprot.txt Catalyzes the conversion of L-tyrosine to L- file:human/TH/TH-uniprot.txt dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the |
| GO:0001963 synaptic transmission, dopaminergic | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dopaminergic synaptic transmission is a downstream consequence of TH providing the rate-limiting precursor for dopamine synthesis, rather than TH's own molecular activity. Genuine but peripheral to the core enzymatic function. |
| GO:0007617 mating behavior | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Behavioral term inferred from orthologs (fly/worm/mouse). A distal, catecholamine-signaling-dependent behavioral output, not a core function of the human enzyme. |
| GO:0042418 epinephrine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: TH catalyzes the rate-limiting committed entry step for all catecholamines, so it contributes to epinephrine biosynthesis, although the direct chemical product is L-DOPA (epinephrine formation additionally requires AADC, DBH and PNMT). Correct upstream-pathway involvement. Supporting Evidence: file:human/TH/TH-uniprot.txt the biosynthesis of catecholamines, dopamine, noradrenaline, and |
| GO:0042421 norepinephrine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: As the rate-limiting committed step of catecholamine biosynthesis, TH is required upstream of norepinephrine formation. Correct pathway involvement (direct product is L-DOPA; norepinephrine also requires AADC and DBH). Supporting Evidence: file:human/TH/TH-uniprot.txt the biosynthesis of catecholamines, dopamine, noradrenaline, and |
| GO:0050890 cognition | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: High-level behavioral/physiological process inferred from orthologs; a distal consequence of dopaminergic signaling, not a core function. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: TH is a soluble cytosolic enzyme; the cytoplasm is its principal site of action. Correct core cellular location, supported by direct evidence. Supporting Evidence: file:human/TH/TH-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0006585 dopamine biosynthetic process from tyrosine | IBA GO_REF:0000033 | ACCEPT | Summary: The most precise biological-process term for TH: it performs the first (rate-limiting) step of dopamine synthesis from L-tyrosine. This is a core BP and matches the UniProt PATHWAY statement. Supporting Evidence: file:human/TH/TH-uniprot.txt Catecholamine biosynthesis; dopamine biosynthesis; dopamine file:human/TH/TH-uniprot.txt from L-tyrosine: step 1/2 |
| GO:0030424 axon | IBA GO_REF:0000033 | ACCEPT | Summary: TH is present and active in the axons and axon terminals of catecholaminergic neurons, where much of catecholamine synthesis occurs. Consistent with the UniProt subcellular location (axon, dopaminergic axon terminals). Supporting Evidence: file:human/TH/TH-uniprot.txt Cell projection, axon |
| GO:0043204 perikaryon | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Neuronal cell-body localization inferred from orthologs; TH is present in the soma as well as axons of catecholaminergic neurons. A valid but non-core, compartment-refinement location. |
| GO:0004497 monooxygenase activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Correct but general parent of the specific tyrosine 3-monooxygenase activity that is separately annotated. Redundant with the more informative GO:0004511. |
| GO:0004511 tyrosine 3-monooxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assertion of the defining molecular function (via InterPro/EC/RHEA). Correct core MF; matches abundant experimental evidence for this gene. Supporting Evidence: file:human/TH/TH-uniprot.txt EC=1.14.16.2 |
| GO:0005506 iron ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: TH is a non-heme iron enzyme that binds a catalytic Fe(II) ion (cofactor Fe2+; iron-coordinating residues His361, His366, Glu406). Correct core MF required for catalysis. Supporting Evidence: file:human/TH/TH-uniprot.txt Name=Fe(2+); Xref=ChEBI:CHEBI:29033 |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization is a minor, phosphorylation-dependent pool (Ser19-phospho TH shows a nuclear distribution). UniProt lists Nucleus. Real but not the core catalytic location. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (SubCell) assertion of the correct core cytoplasmic location of this soluble enzyme. Consistent with experimental and phylogenetic evidence. Supporting Evidence: file:human/TH/TH-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: From UniProt subcellular location (secretory/synaptic vesicle, By similarity). A transport-associated pool in neurons; valid but non-core relative to the cytosolic catalytic location. |
| GO:0009072 aromatic amino acid metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Correct but very general parent process (TH hydroxylates the aromatic amino acid tyrosine). Subsumed by the more specific dopamine/catecholamine biosynthesis terms. |
| GO:0016714 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 | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Accurate mechanistic parent term describing the pteridine-dependent monooxygenase chemistry of TH, but subsumed by the specific tyrosine 3-monooxygenase activity that is separately annotated. |
| GO:0030424 axon | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (SubCell) axon location, consistent with UniProt and with the IBA axon annotation. Correct location for this neuronal enzyme. Supporting Evidence: file:human/TH/TH-uniprot.txt Cell projection, axon |
| GO:0042423 catecholamine biosynthetic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Correct general parent process; TH is the rate-limiting entry enzyme for catecholamine biosynthesis. Subsumed by the more specific dopamine biosynthesis terms, so retained as non-core. |
| GO:0043005 neuron projection | IEA GO_REF:0000117 | ACCEPT | Summary: TH localizes to neuron projections (axons/terminals) of catecholaminergic neurons. Correct location, consistent with UniProt and with the IDA annotation from PMID:17135716. Supporting Evidence: file:human/TH/TH-uniprot.txt Cell projection, axon |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: From UniProt subcellular location (Cytoplasm, perinuclear region). A compartment refinement within the cytoplasm; valid but non-core. |
| GO:0007601 visual perception | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from mouse ortholog (P24529) of a distal retinal/visual role. A downstream, tissue-specific developmental consequence, not a core function. |
| GO:0042462 eye photoreceptor cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from mouse ortholog of a retinal developmental role (dopaminergic amacrine/photoreceptor context). Peripheral, tissue-specific, not core. |
| GO:0048596 embryonic camera-type eye morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from mouse ortholog of an eye-morphogenesis role. Distal developmental consequence of catecholamine signaling, not a core function. |
| GO:1990384 hyaloid vascular plexus regression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: From the mouse ortholog function ("Positively regulates the regression of retinal hyaloid vessels during postnatal development", By similarity). A peripheral developmental role, not core to the enzymatic function. Supporting Evidence: file:human/TH/TH-uniprot.txt Positively regulates |
| GO:0042416 dopamine biosynthetic process | IDA PMID:17391063 Characterisation of novel splicing variants of the tyrosine ... | ACCEPT | Summary: Direct evidence that TH functions in dopamine biosynthesis; this paper characterized catalytically active vs inactive C-terminal splice variants of human TH and confirmed the catecholamine biosynthesis pathway role. Core BP. Supporting Evidence: file:human/TH/TH-uniprot.txt PATHWAY: Catecholamine biosynthesis; dopamine biosynthesis; dopamine |
| GO:0042416 dopamine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assertion (ARBA/UniPathway) of the correct core dopamine biosynthesis role, redundant with the IDA annotation to the same term. Supporting Evidence: file:human/TH/TH-uniprot.txt Catecholamine biosynthesis; dopamine biosynthesis; dopamine |
| GO:0005829 cytosol | TAS Reactome:R-HSA-209823 | ACCEPT | Summary: Reactome-traceable assertion of the cytosolic location where TH hydroxylates tyrosine to L-DOPA. Correct core location. Supporting Evidence: file:human/TH/TH-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0005515 protein binding | IPI PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from an interaction with DJ-1/PARK7 (Q99497), which directly binds and positively regulates TH activity. The interaction is real, but the term is uninformative about TH's function. Retained (experimental IPI) but flagged as over-annotated; the specific regulatory partner is better captured by the enzyme-binding annotation. |
| GO:0004511 tyrosine 3-monooxygenase activity | EXP PMID:15287903 Effects of phosphorylation by protein kinase A on binding of... | ACCEPT | Summary: Direct experimental characterization of human TH catalytic activity and its regulation by PKA phosphorylation and catecholamine binding. Core molecular function. Supporting Evidence: PMID:15287903 Tyrosine hydroxylase (TyrH), the catalyst for the key regulatory step in catecholamine biosynthesis |
| GO:0004511 tyrosine 3-monooxygenase activity | EXP PMID:17391063 Characterisation of novel splicing variants of the tyrosine ... | ACCEPT | Summary: Direct experimental assay of the catalytic activity of human TH splice variants (active full-length isoforms vs catalytically inactive C-terminal variants). Core molecular function. |
| GO:0004511 tyrosine 3-monooxygenase activity | EXP PMID:24753243 Functional studies of tyrosine hydroxylase missense variants... | ACCEPT | Summary: Direct experimental measurement of TH enzyme activity (Km, Vmax, thermal stability) for wild-type and many disease variants of recombinant human TH. Core molecular function. Supporting Evidence: PMID:24753243 an aromatic amino acid hydroxylase (AAAH) that catalyzes the rate-limiting step in the synthesis of the catecholamines |
| GO:0004511 tyrosine 3-monooxygenase activity | EXP PMID:34922205 Tyrosine hydroxylase activity is regulated through the modif... | ACCEPT | Summary: Direct experimental assay of human TH activity (including Km/Vmax for L-tyrosine and BH4) and its inactivation by cysteine (Cys176/Cys207) modification. Core molecular function. Supporting Evidence: PMID:34922205 Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of dopamine |
| GO:0004511 tyrosine 3-monooxygenase activity | EXP PMID:8528210 Recessively inherited L-DOPA-responsive dystonia caused by a... | ACCEPT | Summary: Direct measurement of catalytic activity of recombinant human TH (wild-type and the Q381K/Q412K disease mutant), confirming the tyrosine-to-L-DOPA activity. Core molecular function. Supporting Evidence: PMID:8528210 Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of dopamine |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of nuclear localization from mouse ortholog P04177. Corresponds to a minor Ser19-phosphorylation-dependent nuclear pool; valid but non-core. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of the correct core cytoplasmic location from the mouse ortholog. Consistent with all other evidence. Supporting Evidence: file:human/TH/TH-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, perinuclear region |
| GO:0004511 tyrosine 3-monooxygenase activity | IDA PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | ACCEPT | Summary: Direct assay of TH activity in human dopaminergic cells (SH-SY5Y), showing DJ-1 directly binds and positively regulates TH. Confirms the core catalytic activity of human TH. Supporting Evidence: PMID:19703902 DJ-1 directly bound to TH and DDC and positively regulated their activities in human dopaminergic cells |
| GO:0042416 dopamine biosynthetic process | IDA PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | ACCEPT | Summary: Direct evidence that TH participates in dopamine synthesis in human dopaminergic cells (DJ-1-dependent activation of dopamine synthesis via TH). Core BP. Supporting Evidence: PMID:19703902 Parkinson disease (PD) is caused by loss of dopamine, which is synthesized from tyrosine by two enzymes, tyrosine hydroxylase (TH) |
| GO:0005634 nucleus | IDA PMID:21392500 Phosphorylation of the N-terminal portion of tyrosine hydrox... | KEEP AS NON CORE | Summary: Direct localization of Ser19-phosphorylated TH predominantly to the nucleus (in PC12D cells). A phosphorylation-state-dependent minor pool; retained as non-core relative to the cytosolic catalytic location. Supporting Evidence: PMID:21392500 those molecules phosphorylated at Ser19 were found mainly in the nucleus |
| GO:0005737 cytoplasm | IDA PMID:21392500 Phosphorylation of the N-terminal portion of tyrosine hydrox... | ACCEPT | Summary: Direct evidence for cytoplasmic localization of TH (Ser31/Ser40-phospho forms predominate in the cytoplasm of PC12D cells). Correct core location. Supporting Evidence: PMID:21392500 TH molecules phosphorylated at their Ser31 and Ser40 were localized predominantly in the cytoplasm |
| GO:0004511 tyrosine 3-monooxygenase activity | IDA PMID:1680128 Phosphorylation of human recombinant tyrosine hydroxylase is... | ACCEPT | Summary: Direct assay of the catalytic activity and specific activities of purified recombinant human TH isoforms 1 and 2, including cofactor (BH4) and substrate (tyrosine) kinetics. Core molecular function. Supporting Evidence: PMID:1680128 the specific activities of TH-1 and TH-2 are 1300 and 620 nmol of dihydroxyphenylalanine/min/mg |
| GO:0048471 perinuclear region of cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse ortholog P24529 of the perinuclear cytoplasmic location (matches UniProt). A compartment refinement; non-core. |
| GO:1990384 hyaloid vascular plexus regression | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer from mouse ortholog of the postnatal retinal hyaloid vessel regression role. Peripheral developmental function, not core. Supporting Evidence: file:human/TH/TH-uniprot.txt Positively regulates |
| GO:0019899 enzyme binding | IPI PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | KEEP AS NON CORE | Summary: TH binds DJ-1/PARK7 (DJ-1 directly binds TH and activates it). This is a genuine regulatory protein-protein interaction but "enzyme binding" describes a regulatory partnership, not TH's own catalytic function. Retained as non-core. Supporting Evidence: PMID:19703902 DJ-1 directly bound to TH and DDC and positively regulated their activities |
| GO:0001666 response to hypoxia | IDA PMID:17520326 Oxygen dependence of tyrosine hydroxylase. | MARK AS OVER ANNOTATED | Summary: The cited paper is an in vitro enzymology study of the oxygen (O2) Km of purified human TH isoforms (oxygen dependence of catalysis), demonstrating that TH activity can be limited by low oxygen. It does not measure a cellular "response to hypoxia" (a stimulus-response biological process). The GO term is therefore an over-interpretation of enzyme oxygen-kinetics data. Retained (experimental IDA) but flagged as over-annotated. Supporting Evidence: PMID:17520326 TH activity may be severely limited by oxygen availability even at moderate hypoxic conditions |
| GO:0001963 synaptic transmission, dopaminergic | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of the dopaminergic synaptic transmission role. A downstream consequence of TH-dependent dopamine supply; genuine but non-core. |
| GO:0003007 heart morphogenesis | NAS PMID:12113410 Association between tyrosine hydroxylase polymorphisms and l... | KEEP AS NON CORE | Summary: Non-traceable assertion based on a human association study linking a TH Val81Met polymorphism to left-ventricular mass. An indirect, sympathetic-tone-mediated effect on heart structure, not a direct developmental function of the enzyme. |
| GO:0004511 tyrosine 3-monooxygenase activity | IDA PMID:11943812 A role for alpha-synuclein in the regulation of dopamine bio... | ACCEPT | Summary: Direct assay of TH activity in a cell-free system (regulation by alpha-synuclein), confirming the catalytic activity of TH. Core molecular function. Supporting Evidence: PMID:11943812 14-3-3 binds to and activates tyrosine hydroxylase, the rate-limiting enzyme in dopamine (DA) biosynthesis |
| GO:0004511 tyrosine 3-monooxygenase activity | IDA PMID:12631248 Tyrosine hydroxylase isoenzyme I is present in human melanos... | ACCEPT | Summary: Direct measurement of TH enzyme activity in human melanosomal extracts, confirming L-DOPA production. Core molecular function (in a peripheral, melanocyte context). Supporting Evidence: PMID:12631248 enzyme activities for both tyrosine hydroxylase and tyrosinase were measured in the same preparations |
| GO:0004511 tyrosine 3-monooxygenase activity | IDA PMID:2896667 Expression of human tyrosine hydroxylase cDNA in invertebrat... | ACCEPT | Summary: Direct assay of recombinant human TH activity expressed in insect (SF9) cells, with substrate/cofactor kinetics matching the native enzyme. Core molecular function. Supporting Evidence: PMID:2896667 Characterization of tyrosine hydroxylase activity in infected SF9 cells demonstrated both substrate and cofactor kinetics |
| GO:0005515 protein binding | IPI PMID:11943812 A role for alpha-synuclein in the regulation of dopamine bio... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from the TH-alpha-synuclein (SNCA, P37840) interaction, which inhibits TH activity. Real interaction, but the term is uninformative. Retained (experimental IPI) and flagged as over-annotated. |
| GO:0005790 smooth endoplasmic reticulum | IDA PMID:12457228 Ultrastructural localization of tyrosine hydroxylase in huma... | KEEP AS NON CORE | Summary: Ultrastructural localization of TH in human PBMCs (plasma membrane and cytoplasmic granules). The abstract does not specifically place TH in the smooth endoplasmic reticulum; this is a weakly supported, peripheral (non-neuronal) localization. Retained (experimental IDA) but non-core; the core location remains the cytosol. |
| GO:0006585 dopamine biosynthetic process from tyrosine | NAS PMID:10907721 Specific localization of the guanosine triphosphate (GTP) cy... | ACCEPT | Summary: Non-traceable assertion of the tyrosine-to-dopamine role in the context of a human brain TH/GCH1 co-localization study. Matches the core BP; retained as a correct (if non-experimental) statement of the core function. Supporting Evidence: file:human/TH/TH-uniprot.txt from L-tyrosine: step 1/2 |
| GO:0007507 heart development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer reflecting the mouse Th-knockout phenotype (embryos die of apparent cardiovascular failure). An indirect, catecholamine-mediated developmental requirement, not a core enzymatic function. |
| GO:0007601 visual perception | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of a distal visual/retinal role. Peripheral, tissue-specific consequence of dopaminergic signaling; non-core. |
| GO:0007612 learning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Behavioral term transferred from ortholog; a distal consequence of catecholamine signaling, not a core function. |
| GO:0007613 memory | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Behavioral term transferred from ortholog; distal, catecholamine-dependent output, not a core function. |
| GO:0007626 locomotory behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Behavioral term transferred from ortholog; motor behavior depends on dopaminergic signaling downstream of TH. Genuine but non-core. |
| GO:0008016 regulation of heart contraction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of a physiological role reflecting sympathetic (catecholaminergic) control of heart contraction. Indirect and non-core. |
| GO:0009887 animal organ morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: General developmental process transferred from ortholog, reflecting catecholamine requirements in development. Indirect and non-core. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:12457228 Ultrastructural localization of tyrosine hydroxylase in huma... | KEEP AS NON CORE | Summary: Direct localization of TH to the plasma membrane in unstimulated human PBMCs. An unusual, context-specific (non-neuronal, immune-cell) localization; retained (experimental IDA) but non-core. Supporting Evidence: PMID:12457228 In unstimulated PBMCs, TH-specific immunoreactivity was localized to the plasma membrane |
| GO:0031410 cytoplasmic vesicle | IDA PMID:12457228 Ultrastructural localization of tyrosine hydroxylase in huma... | KEEP AS NON CORE | Summary: Direct localization of TH to electron-dense cytoplasmic granules in PHA-stimulated human PBMCs. Consistent with a vesicle-associated pool; retained as non-core relative to the cytosolic catalytic location. Supporting Evidence: PMID:12457228 TH immunoreactivity was almost completely localized to electron-dense cytoplasmic granules |
| GO:0033162 melanosome membrane | IDA PMID:12631248 Tyrosine hydroxylase isoenzyme I is present in human melanos... | KEEP AS NON CORE | Summary: Direct localization of TH isoenzyme I to the membrane of melanosomes in human epidermal melanocytes, where it may supply L-DOPA to tyrosinase. Peripheral, tissue-specific location; non-core. Supporting Evidence: PMID:12631248 The melanosomal membrane location of tyrosine hydroxylase together with tyrosinase |
| GO:0042416 dopamine biosynthetic process | IDA PMID:12457228 Ultrastructural localization of tyrosine hydroxylase in huma... | ACCEPT | Summary: TH-dependent catecholamine synthesis was demonstrated in human PBMCs (increased intracellular catecholamine content upon stimulation). Supports the core dopamine biosynthesis role in a peripheral context. Supporting Evidence: PMID:12457228 increased intracellular catecholamine content, suggesting the occurrence of TH upregulation |
| GO:0042418 epinephrine biosynthetic process | IDA PMID:12457228 Ultrastructural localization of tyrosine hydroxylase in huma... | ACCEPT | Summary: TH contributes upstream to catecholamine (including epinephrine) synthesis in human PBMCs. Correct pathway involvement (TH provides the rate-limiting step; epinephrine formation requires additional downstream enzymes). Supporting Evidence: PMID:12457228 the rate-limiting enzyme in the biosynthesis of catecholamines |
| GO:0042421 norepinephrine biosynthetic process | IDA PMID:12457228 Ultrastructural localization of tyrosine hydroxylase in huma... | ACCEPT | Summary: TH contributes upstream to catecholamine (including norepinephrine) synthesis in human PBMCs. Correct pathway involvement (direct product is L-DOPA; norepinephrine also requires AADC and DBH). Supporting Evidence: PMID:12457228 the rate-limiting enzyme in the biosynthesis of catecholamines |
| GO:0042462 eye photoreceptor cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of a retinal developmental role. Peripheral, tissue-specific; non-core. |
| GO:0043005 neuron projection | IDA PMID:17135716 Co-expression of tyrosine hydroxylase and GTP cyclohydrolase... | ACCEPT | Summary: TH is expressed in human neurosecretory neurons (supraoptic nucleus) with co-expression of GCH1 indicating active TH; consistent with a neuron-projection location. Correct location for this neuronal enzyme. Supporting Evidence: file:human/TH/TH-uniprot.txt Cell projection, axon |
| GO:0043204 perikaryon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of the neuronal cell-body (perikaryon) localization. A valid compartment refinement; non-core relative to the cytosol. |
| GO:0043473 pigmentation | TAS PMID:12631248 Tyrosine hydroxylase isoenzyme I is present in human melanos... | KEEP AS NON CORE | Summary: TH in melanosomes may contribute L-DOPA to promote tyrosinase activity and pigmentation. A peripheral, tissue-specific (melanocyte) role; non-core. Supporting Evidence: PMID:12631248 a direct function for tyrosine hydroxylase in the melanosome via a concerted action with tyrosinase to promote pigmentation |
| GO:0045471 response to ethanol | IDA PMID:18343820 Glial cell line-derived neurotrophic factor reverses ethanol... | KEEP AS NON CORE | Summary: Ethanol increases TH protein levels/immunoreactivity via the cAMP/PKA pathway and HSP90 association in SH-SY5Y cells (reversed by GDNF). TH is the responder; a genuine but peripheral response process, not a core function. Supporting Evidence: PMID:18343820 the increase in TH levels in the presence of ethanol required the activation of the cAMP/PKA pathway |
| GO:0048596 embryonic camera-type eye morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of an eye-morphogenesis role from mouse ortholog. Distal developmental consequence; non-core. |
| GO:0004511 tyrosine 3-monooxygenase activity | IDA PMID:16338639 The assays of activities and function of TH, AADC, and GCH1 ... | ACCEPT | Summary: Direct assay of human TH activity (dopamine synthesis together with GCH1 and AADC), confirming the catalytic function. Core molecular function. Supporting Evidence: PMID:16338639 a simple, fast, and reliable method to assay the activities of TH and AADC |
| GO:0005737 cytoplasm | IDA PMID:10907721 Specific localization of the guanosine triphosphate (GTP) cy... | ACCEPT | Summary: Immunohistochemical localization of TH in cell bodies and fibers of monoaminergic neurons of the human brain (cytoplasmic staining). Consistent with the core cytoplasmic location. Supporting Evidence: PMID:10907721 immunoreactivity was observed in the cell bodies and fibers of monoaminergic neurons of the human brain |
| GO:0009653 anatomical structure morphogenesis | TAS PMID:7715703 Targeted disruption of the tyrosine hydroxylase gene reveals... | KEEP AS NON CORE | Summary: Traceable assertion based on the mouse Th-knockout study, in which loss of TH (catecholamines) causes mid-gestational lethality and developmental failure. A very general developmental term reflecting an indirect, catecholamine-mediated requirement; non-core. Supporting Evidence: PMID:7715703 catecholamines are essential for mouse fetal development and postnatal survival |
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