Literature summary for 4.1.1.22 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 hdc, located on chromosome 15q21.2, different splicing products, sequence comparisons, regulatory cis elements in the human HDC promoter (TATA, GC, CACC, Sp1 and GATA boxes): two cis-elements are located between the positions -855 and -821 with respect to the transcription start point that regulates the transcription of the HDC in human basophilic cells. Other regulatory elements are located in position -500 and between positions -532 and -497. The HDC promoter also contains a CpG island involved in epigenetic regulation of its expression during the differentiation of histamine-producing cells	Homo sapiens

Cloned (Comment)

Organism

gene hdc, located on chromosome 15q21.2, different splicing products, sequence comparisons, regulatory cis elements in the human HDC promoter (TATA, GC, CACC, Sp1 and GATA boxes): two cis-elements are located between the positions -855 and -821 with respect to the transcription start point that regulates the transcription of the HDC in human basophilic cells. Other regulatory elements are located in position -500 and between positions -532 and -497. The HDC promoter also contains a CpG island involved in epigenetic regulation of its expression during the differentiation of histamine-producing cells

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	the mutation of a stop codon after W317 in gene hdc leads to a truncated enzyme and the Tourette syndrome	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
4(5)-aminooxymethylimidazole	O-IMHA, a substrate analogue	Homo sapiens
alpha-Fluoromethylhistidine	-	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
methyl L-histidinate	the compound is able to block the reaction at the Michaelis complex step in HDC	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 alpha-fluoromethylhistidine	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
endoplasmic reticulum lumen	the C-terminus is probably required for sorting the enzyme to the endoplasmic reticulum (ER), after which it can be removed to render the active form of the enzyme located in ER lumen	Homo sapiens	5788	-

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
additional information	-	processing intermediates of about 63 kDa with potential residual activity are observed in some cell types	Homo sapiens
53000	55000	active enzyme form	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P19113	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
proteolytic modification	the processing to the active form of mammalian HDC relies on the proteinase activity of caspase 9 and the tandem aspartate residues Asp517-Asp518, Asp550-Asp551	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	substancia nigra and hypothalamus	Homo sapiens	-
colon	sigmoid and transverse	Homo sapiens	-
hypothalamus	-	Homo sapiens	-
ileum	terminal	Homo sapiens	-
kidney	cortex	Homo sapiens	-
lung	-	Homo sapiens	-
additional information	human HDC expression is mainly detected in hypothalamus, lung and stomach in comparison with the rest of the tissues	Homo sapiens	-
stomach	HDC expression regulation in histamine producing gastric cells	Homo sapiens	-

Substrates and Products (Substrate)

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

Subunits

Subunits	Comment	Organism
dimer	structure analysis, overview	Homo sapiens
More	the 150 amino acid long C-terminal region present in mammalian HDC but absent in homologous Gram-negative bacteria HDC and all mammalian DDCs. The C-terminus has not got a well-defined secondary structure and it must be removed to reach the active conformation of mammalian HDC. The C-terminus is probably required for sorting the enzyme to the endoplasmic reticulum (ER), after which it can be removed to render the active form of the enzyme located in ER lumen	Homo sapiens

Synonyms

Synonyms	Comment	Organism
HDC	-	Homo sapiens

Cofactor

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

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.0002	-	pH and temperature not specified in the publication	Homo sapiens	4(5)-aminooxymethylimidazole

Expression

Organism	Comment	Expression
Homo sapiens	HDC transcription is repressed by Kruppel-like factor 4 (KLF4) interacting at the level of Sp1 binding site, and by the nuclear factors Ying-yang 1 and SREBP-1a that interact with the GC box. The histone acetyl transferases KAT5 (also named as TIP60) and HDAC7 seem to be involved in this mechanisms of KLF4-mediated HDC repression acting as corepressors	down
Homo sapiens	in histamine producing immune cells, HDC expression is modulated by a long list of different stimulus, including lipopolysaccharydes, polypeptides (for instance, neuropeptide P, cytokines), inflammation regulators (for instance, phorbolesters plus dexamethasone), or other compounds (for instance, the intracelular levels of polyamines). Helicobacter pylori infection promotes HDC expression through a signaling pathway involving the trans-elements Rap1 and beta-ra	up

General Information

General Information	Comment	Organism
malfunction	truncated forms of the enzyme are related to the Gilles de la Tourette syndrome, phenotype MIM number 137580. Single nucleotide polymorphisms are related to nicotine dependence and other additive behaviors. Gene-disease associations and common pathologies, detailed overview	Homo sapiens
additional information	structural and functional analogies and differences between histidine decarboxylase and aromatic L-amino acid decarboxylase (EC 4.1.1.28) 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 histamine. It is involved in common physiological functions, such as neurotransmission, gastrointestinal track function, immunity, cell growth and cell differentiation. Tissue-specific and time-specific transcriptional HDC regulation must exist, as it behaves as an inducible gene expressed in a very reduced set of cell types. The complexity of HDC expression regulatory mechanisms is also increased by the fact that the enzyme needs to be activated by proteolytic processing and posttranscriptional regulatory mechanisms at the level the enzyme turnover level cannot be discarded. Memory seems to be an important physiological function involving histamine, dopamine, and serotonin	Homo sapiens