DDC encodes aromatic-L-amino-acid decarboxylase (AADC; also known as DOPA decarboxylase, DDC), a cytosolic, pyridoxal 5'-phosphate (PLP)-dependent homodimeric decarboxylase (EC 4.1.1.28) of the group II decarboxylase family. It acts at the branch point of monoamine neurotransmitter biosynthesis, catalyzing the decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) to dopamine in the catecholamine branch and of 5-hydroxy-L-tryptophan (5-HTP) to serotonin in the indoleamine branch, and it can also decarboxylate other aromatic amino acids. Because dopamine is the precursor of noradrenaline and adrenaline and serotonin is the precursor of melatonin, DDC activity is shared across the catecholamine and serotonin/melatonin pathways. The enzyme is a homodimer that binds PLP through a Schiff base to an active-site lysine. Loss of DDC function causes aromatic L-amino-acid decarboxylase deficiency (AADCD), a severe autosomal-recessive inborn error of neurotransmitter metabolism with combined serotonin and catecholamine deficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004058 aromatic-L-amino-acid decarboxylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Correct core molecular function. This is the defining catalytic activity of DDC/AADC (EC 4.1.1.28), the decarboxylation of aromatic L-amino acids. The phylogenetic (IBA) call is consistent with UniProt and with direct experimental annotations (IDA, PMID:16338639) and TAS support (PMID:7567987). Supporting Evidence: file:human/DDC/DDC-uniprot.txt Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Correct subcellular localization. AADC is a soluble cytosolic enzyme; the IBA cytoplasm call is consistent with the Reactome cytosol annotations and with the enzyme's role as a cytosolic decarboxylase. Cytosol (GO:0005829) is the more precise term. Supporting Evidence: file:human/DDC/DDC-uniprot.txt GO:0005829; C:cytosol |
| GO:0006584 catecholamine metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process. DDC catalyzes the final step of dopamine synthesis (L-DOPA to dopamine), and dopamine is a catecholamine, so DDC is genuinely involved in catecholamine metabolism. The more specific child term dopamine biosynthetic process (GO:0042416) is also annotated. Kept as an accurate parent-level BP. Supporting Evidence: file:human/DDC/DDC-uniprot.txt Catecholamine biosynthesis; dopamine biosynthesis; dopamine |
| GO:0042427 serotonin biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process. DDC catalyzes the final step of serotonin synthesis (5-hydroxy-L-tryptophan to serotonin), placing it in the indoleamine branch of monoamine neurotransmitter biosynthesis. Supported by UniProt FUNCTION and by the serotonin catalytic activity. Supporting Evidence: file:human/DDC/DDC-uniprot.txt L-5-hydroxytryptophan to serotonin |
| GO:0004058 aromatic-L-amino-acid decarboxylase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Correct core molecular function, here derived by EC-to-GO mapping (EC 4.1.1.28). This is DDC's own defining activity, not an over-annotation; it is redundant with the IBA/IDA/TAS annotations to the same term. Accept. Supporting Evidence: file:human/DDC/DDC-uniprot.txt EC=4.1.1.28 |
| GO:0006520 amino acid metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Not incorrect but very general: DDC consumes aromatic L-amino acids (L-DOPA, 5-HTP) as substrates, so amino acid metabolism is a true parent process. It is far less informative than the specific dopamine/serotonin/catecholamine biosynthetic process terms and is not a core descriptor of DDC function. Supporting Evidence: file:human/DDC/DDC-uniprot.txt Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine |
| GO:0016830 carbon-carbon lyase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Correct but over-general grouping term. As a decarboxylase, DDC is a carbon-carbon lyase, but this high-level MF conveys little about the enzyme's specificity. The specific aromatic-L-amino-acid decarboxylase activity term should be used to describe the function. Supporting Evidence: file:human/DDC/DDC-uniprot.txt Decarboxylase |
| GO:0016831 carboxy-lyase activity | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Correct but over-general grouping term (a direct parent of the decarboxylase activities). DDC is a carboxy-lyase (decarboxylase), but the specific aromatic-L-amino-acid decarboxylase activity term is the informative descriptor. Supporting Evidence: file:human/DDC/DDC-uniprot.txt Decarboxylase |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: Correct core cofactor-binding function. DDC is a PLP-dependent enzyme; the crystal structure (PMID:22143761) defines the PLP-binding residues and the Lys303 internal aldimine. Although annotated by IEA here, this is a well-established, structurally verified activity and a core descriptor. Supporting Evidence: file:human/DDC/DDC-uniprot.txt Name=pyridoxal 5'-phosphate |
| GO:0036467 5-hydroxy-L-tryptophan decarboxylase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Correct specific molecular function (serotonin branch), derived by Rhea/reaction mapping (RHEA:18533). This matches the UniProt catalytic activity 5-hydroxy-L-tryptophan to serotonin and is also supported experimentally (IDA) and by ISS. Core activity. Supporting Evidence: file:human/DDC/DDC-uniprot.txt 5-hydroxy-L-tryptophan + H(+) = serotonin + CO2 |
| GO:0036468 L-dopa decarboxylase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Correct specific molecular function (dopamine branch), derived by Rhea/reaction mapping (RHEA:12272). Matches the UniProt catalytic activity L-dopa to dopamine and is also supported experimentally (IDA, PMID:19703902) and by ISS. Core activity. Supporting Evidence: file:human/DDC/DDC-uniprot.txt L-dopa + H(+) = dopamine + CO2 |
| GO:0042401 biogenic amine biosynthetic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Accurate but general parent process (ARBA prediction). DDC produces the biogenic amines dopamine and serotonin, so this is correct; however it is subsumed by the more specific dopamine and serotonin biosynthetic process terms and is not the core descriptor. Supporting Evidence: file:human/DDC/DDC-uniprot.txt Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine |
| GO:0005515 protein binding | IPI PMID:12864730 Isolation and identification of L-dopa decarboxylase as a pr... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" is uninformative and does not describe DDC's core function. The underlying interaction is real: DDC was identified as an androgen receptor (AR, P10275)-interacting protein that enhances AR transcriptional activity in prostate cancer cells, a proposed moonlighting coactivator role distinct from its enzymatic function. Retained (not removed, per policy for experimental IPI) but flagged as over-annotated; the specific AR-modulatory role belongs in a more informative term/note. Supporting Evidence: PMID:12864730 DDC (L-dopa decarboxylase) was detected multiple times as a novel AR-interacting |
| GO:0042416 dopamine biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: Core biological process. DDC catalyzes the second and final step of dopamine biosynthesis (L-DOPA to dopamine). The ISS call (from ortholog P80041) is consistent with the direct experimental annotation (IDA, PMID:19703902) to the same term. Supporting Evidence: file:human/DDC/DDC-uniprot.txt from L-tyrosine: step 2/2 |
| GO:0042416 dopamine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: Core biological process, here inferred via UniPathway mapping (UPA00747). Redundant with the ISS and IDA annotations to the same term. Correct core pathway role. Supporting Evidence: file:human/DDC/DDC-uniprot.txt from L-tyrosine: step 2/2 |
| 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" is uninformative. The interaction is real and experimentally supported: DJ-1 (PARK7, Q99497) directly binds DDC and positively regulates its activity. Retained (not removed, per policy for experimental IPI) but flagged as over-annotated; the DJ-1 interaction is better represented by the enzyme binding annotation and the description of the DJ-1/TH/DDC complex. Supporting Evidence: PMID:19703902 we found that DJ-1 directly bound to TH and DDC and positively regulated their activities in human dopaminergic cells |
| GO:0036467 5-hydroxy-L-tryptophan decarboxylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Correct specific molecular function (serotonin branch), transferred by sequence similarity from ortholog P80041. Consistent with the UniProt catalytic activity and with the IDA annotation to the same term. Core activity. Supporting Evidence: file:human/DDC/DDC-uniprot.txt 5-hydroxy-L-tryptophan + H(+) = serotonin + CO2 |
| GO:0036468 L-dopa decarboxylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Correct specific molecular function (dopamine branch), transferred by sequence similarity from ortholog P80041. Consistent with the UniProt catalytic activity and the IDA annotation to the same term. Core activity. Supporting Evidence: file:human/DDC/DDC-uniprot.txt L-dopa + H(+) = dopamine + CO2 |
| GO:0036468 L-dopa decarboxylase activity | IDA PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | ACCEPT | Summary: Direct experimental support for the core dopamine-branch activity. This study measured DDC (L-DOPA decarboxylase) activity in human dopaminergic cells as part of characterizing DJ-1-dependent stimulation of dopamine synthesis. Core activity; accept. Supporting Evidence: PMID:19703902 we found that 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 experimental support for the core dopamine biosynthetic process. The study demonstrates DDC's role in dopamine synthesis in human dopaminergic cells (as one of the two enzymes, with TH, that synthesize dopamine from tyrosine). Core process; accept. Supporting Evidence: PMID:19703902 dopamine, which is synthesized from tyrosine by two enzymes, tyrosine hydroxylase (TH) and |
| GO:0036467 5-hydroxy-L-tryptophan decarboxylase activity | IDA PMID:16338639 The assays of activities and function of TH, AADC, and GCH1 ... | ACCEPT | Summary: Direct assay-based annotation of AADC activity. This methods paper developed an assay for hAADC activity in the context of dopamine-synthesis gene therapy; the abstract foregrounds dopamine, but AADC decarboxylates both L-DOPA and 5-HTP, and this is an experimental (IDA) annotation made by the curator from the full assay data. Retained as core activity; not removed. Supporting Evidence: PMID:16338639 assay the activities of TH and AADC |
| GO:0019899 enzyme binding | IPI PMID:19703902 Oxidative status of DJ-1-dependent activation of dopamine sy... | KEEP AS NON CORE | Summary: Experimentally supported protein interaction, more informative than bare "protein binding". The IPI is to tyrosine hydroxylase (TH, P07101): the study reports a ternary complex among DJ-1, TH and DDC in dopaminergic cells. This is a regulatory/complex interaction with a partner enzyme in the same pathway, not DDC's core catalytic function; kept as non-core. Supporting Evidence: PMID:19703902 A ternary complex among DJ-1, TH, and DDC was found |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: High-throughput proteomic detection of DDC in human urinary exosomes. Plausible for an abundant soluble cytosolic protein captured in secreted vesicles, but this is not where DDC performs its core catalytic function (cytosol). Kept as a non-core, high-throughput localization observation. Supporting Evidence: PMID:19056867 we used LC-MS/MS to profile the proteome of human urinary exosomes |
| GO:0005829 cytosol | TAS Reactome:R-HSA-209859 | ACCEPT | Summary: Correct core localization. AADC acts as a cytosolic homodimer; Reactome places the serotonin-forming decarboxylation reaction in the cytosol. Consistent with the IBA cytoplasm annotation. Supporting Evidence: Reactome:R-HSA-209859 Aromatic L-amino acid decarboxylase (AADC) catalyzes the decarboxylation of both dopa and 5-hydroxytryptophan |
| GO:0005829 cytosol | TAS Reactome:R-HSA-209924 | ACCEPT | Summary: Correct core localization (duplicate of the other Reactome cytosol annotation, from the dopamine-forming reaction). AADC is a cytosolic enzyme. Accept. Supporting Evidence: Reactome:R-HSA-209924 Aromatic L-amino acid decarboxylase (AADC, dopa decarboxylase) decarboxylates dopa to form dopamine |
| GO:0004058 aromatic-L-amino-acid decarboxylase activity | IDA PMID:16338639 The assays of activities and function of TH, AADC, and GCH1 ... | ACCEPT | Summary: Direct experimental (assay-based) support for the core molecular function. This paper developed and applied an assay of human AADC enzymatic activity. Strong core annotation; accept. Supporting Evidence: PMID:16338639 assay the activities of TH and AADC |
| GO:0004058 aromatic-L-amino-acid decarboxylase activity | TAS PMID:7567987 Aromatic-L-amino-acid decarboxylase, a pyridoxal phosphate-d... | ACCEPT | Summary: Author-stated (TAS) support for the core molecular function. This paper identifies AADC (EC 4.1.1.28) and restates its catalytic role in decarboxylating 5-HTP to serotonin and L-DOPA to dopamine. Core activity; accept. Supporting Evidence: PMID:7567987 catalyzes the decarboxylation of L-5-hydroxytryptophan to |
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