Literature summary for 4.1.1.28 extracted from

Sanchez-Jimenez, F.; Pino-Angeles, A.; Rodriguez-Lopez, R.; Morales, M.; Urdiales, J.L.
Structural and functional analogies and differences between histidine decarboxylase and aromatic l-amino acid decarboxylase molecular networks biomedical implications (2016), Pharmacol. Res., 114, 90-102 .

Cloned(Commentary)

Cloned (Comment)	Organism
gene ddc, located on chromosome 7p12.2, sequence comparisons, in addition to a TATA box, a strong promoter is detectedin the human DDC gene. It contains three positive regulatory elements located from position -560 bp to -1. Another two negative regulatory cis-elements are detected in between -9000 and 560 and 396-31. An alternative-promoter mechanism for regulating tissue-specific expression of DDC gene is observed	Homo sapiens

Cloned (Comment)

Organism

gene ddc, located on chromosome 7p12.2, sequence comparisons, in addition to a TATA box, a strong promoter is detectedin the human DDC gene. It contains three positive regulatory elements located from position -560 bp to -1. Another two negative regulatory cis-elements are detected in between -9000 and 560 and 396-31. An alternative-promoter mechanism for regulating tissue-specific expression of DDC gene is observed

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
A275T	naturally occuring mutation involved in aromatic-L-amino-acid decarboxylase deficiency	Homo sapiens
A91V	naturally occuring mutation involved in aromatic-L-amino-acid decarboxylase deficiency	Homo sapiens
F309L	naturally occuring mutation, involved in aromatic-L-amino-acid decarboxylase deficiency	Homo sapiens
G102S	naturally occuring mutation, involved in aromatic-L-amino-acid decarboxylase deficiency	Homo sapiens
R347Q	naturally occuring mutation involved in aromatic-L-amino-acid decarboxylase deficiency	Homo sapiens
S147R	naturally occuring mutation, involved in aromatic-L-amino-acid decarboxylase deficiency	Homo sapiens
S250F	naturally occuring mutation, involved in aromatic-L-amino-acid decarboxylase deficiency	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
carbidopa	the compound is able to block the reaction at the Michaelis complex step in DDC	Homo sapiens
epigallocatechin-3-gallate	EGCG, the inhibitory effect is mediated by blocking the entrance to the catalytic site, therefore, preventing substrate binding	Homo sapiens
additional information	successful strategies to inhibit the decarboxylase have included the synthesis of fluoro-derivatives, which act as competitive and/or suicide inhibitors, as it is the case of several fluoro-dopa derivatives	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-
additional information	the enzyme is associated with the membrane in dopamine pro-ducing cells such as neurons, leukocytes and kidney cancer cells	Homo sapiens	-	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
L-Dopa	Homo sapiens	-	dopamine + CO2	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P20711	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	in substantia nigra	Homo sapiens	-
breast cancer cell	different splicing variants	Homo sapiens	-
colon	sigmoid and transverse	Homo sapiens	-
colonic cancer cell	different splicing variants	Homo sapiens	-
gastric cancer cell	different splicing variants	Homo sapiens	-
ileum	terminal	Homo sapiens	-
kidney	cortex	Homo sapiens	-
kidney cancer cell	different splicing variants	Homo sapiens	-
liver	-	Homo sapiens	-
lung	DDC is expressed in neuroendocrine differentiated cells	Homo sapiens	-
additional information	neuronal and non-neuronal tissues express DDC mRNAs with distinct 5'-UTR due to alternative promotor usage and alternative splicing within the 5'-UTR. Different splicing variants are observed in cancer cells. The human DDC gene is highly expressed in substantia nigra, terminal ileum,colon transverse, kidney cortex, liver, and pancreas	Homo sapiens	-
pancreas	-	Homo sapiens	-
renal proximal tubule	-	Homo sapiens	-
stomach	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
L-Dopa	-	Homo sapiens	dopamine + CO2	-	?

Subunits

Subunits	Comment	Organism
dimer	structure analysis, overview	Homo sapiens
More	a 150 amino acid long C-terminal region is present in mammalian HDC but absent in homologous Gram-negative bacteria HDC and all mammalian DDCs	Homo sapiens

Synonyms

Synonyms	Comment	Organism
AADC	-	Homo sapiens
Aromatic L-amino acid decarboxylase	-	Homo sapiens
DDC	-	Homo sapiens
dopa decarboxilase	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
pyridoxal 5'-phosphate	-	Homo sapiens

Expression

Organism	Comment	Expression
Homo sapiens	in lung, DDC expression in neuroendocrine differentiated cells is upregulated by Notch-1 receptor-elicited signaling	up

General Information

General Information	Comment	Organism
malfunction	gene-disease associations and common pathologies, detailed overview	Homo sapiens
additional information	structural and functional analogies and differences between histidine decarboxylase (EC 4.1.1.22) and aromatic L-amino acid decarboxylase molecular networks, overview. Human histidine decarboxylase (HDC) and dopa decarboxylase (DDC) are highly homologous enzymes responsible for the synthesis of biogenic amines (BA) like histamine, and serotonin and dopamine, respectively	Homo sapiens
physiological function	the enzyme is responsible for the biosynthesis of dopamine. It is involved in common physiological functions, such as neurotransmission, gastrointestinal track function, immunity, cell growth and cell differentiation. Memory seems to be an important physiological function involving histamine, dopamine, and serotonin	Homo sapiens