Literature summary for 1.14.17.3 extracted from

Vishwanatha, K.; Baeck, N.; Mains, R.E.; Eipper, B.A.
A histidine-rich linker region in peptidylglycine alpha-amidating monooxygenase has the properties of a pH sensor (2014), J. Biol. Chem., 289, 12404-12420 .

Search for more literature for 1.14.17.3

Cloned(Commentary)

Cloned (Comment)	Organism
gene PAM, splice variant PAM-1, recombinant expression of GST-tagged wild-type and mutant PAM-1/H3A enzymes in stable AtT-20 and HEK293 cells cell lines, and recombinant expression of GST-tagged wild-type and mutant PAM-1/H3A enzymes Escherichia coli strain BL21	Mus musculus

Protein Variants

Protein Variants	Comment	Organism
H364A/H366A/H367A	site-directed mutagenesis. mutant PAM-1/H3A shows affected trafficking through the endogenous membranes. The PAM-1/H3A mutant exhibits the same pH optimum as the wild-type of pH 4.5, but shows slightly lower activity from pH 5.5-7.0. Mutant PAM-1/H3A and wild-type PAM-1 are processed differently when expressed in AtT-20 corticotrope tumor cells. Proteolytic processing of PAM-1 and PAM-1/H3A in AtT-20 cells is similar. Newly synthesized PAM-1/H3A disappears more quickly than newly synthesized PAM-1 in the cells. The H3A mutation eliminates the ability of internalized PAM-1 to return to secretory granules. Alkalinizing agents show differential effects on PAM-1 and PAM-1/H3A. Phenotype comparisons of wild-type and mutant enzymes and enzyme expressing cells, overview	Mus musculus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
membrane	enzyme PAM is a type I integral membrane protein	Mus musculus	16020	-
additional information	the enzyme is localized to the perinuclear region in a complex reticular pattern resembling that of the Golgi complex	Mus musculus	-	-
secretory granule	-	Mus musculus	30141	-

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	P97467	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant GST-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 by glutathione affinity chromatography, tag cleavage by HRV3C protease overnight, and followed by anion echange chromatography	Mus musculus

Source Tissue

Source Tissue	Comment	Organism	Textmining
AtT-20 cell	-	Mus musculus	-
pituitary gland	-	Mus musculus	-

Subunits

Subunits	Comment	Organism
More	the protease-resistant catalytic core of PHM (PHMcc) is followed by a well conserved cluster of three His residues. This His cluster is included in the final exon encoding PHMcc and is followed by a poorly conserved, protease-sensitive region encoded by a short exon present in each of the major splice variants of PAM. The non-catalytic linker region between PHM and PAL includes a 315-nt exon in PAM-1. Exon 16 plays an important role in PAM-1 trafficking and in the ability of PAM-1 to participate in transmembrane signaling	Mus musculus

Synonyms

Synonyms	Comment	Organism
PAM	-	Mus musculus
PAM-1	-	Mus musculus
peptidylglycine alpha-amidating monooxygenase	-	Mus musculus

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
4.5	-	maximal activity at for wild-type and mutant enzymes	Mus musculus

pH Range

pH Minimum	pH Maximum	Comment	Organism
3	8	activity range, wild-type and mutant enzymes, pH profiles, overview	Mus musculus

General Information

General Information	Comment	Organism
malfunction	mutating the His residues His364, His366, and His367 to Ala in the His-rich cluster (His-Gly-His-His) in the linker region connecting the enzyme's two catalytic domains affects enzyme trafficking. H3A mutation eliminates the ability of internalized PAM-1 to return to secretory granules	Mus musculus
additional information	the protease-resistant catalytic core of PHM (PHMcc) is followed by a well conserved cluster of three His residues. This His cluster is included in the final exon encoding PHMcc and is followed by a poorly conserved, protease-sensitive region encoded by a short exon present in each of the major splice variants of PAM. The non-catalytic linker region between PHM and PAL includes a 315-nt exon in PAM-1. Exon 16 plays an important role in PAM-1 trafficking and in the ability of PAM-1 to participate in transmembrane signaling	Mus musculus
physiological function	decreasing luminal pH is thought to play a role in the entry of newly synthesized and endocytosed membrane proteins into secretory granules. Secretory granule membrane proteins are retrieved and reused or degraded after exocytosis. The two catalytic domains of peptidylglycine alpha-amidating monooxygenase (PAM) catalyze the sequential reactions that convert peptidyl-Gly substrates into amidated products. A conserved His-rich cluster (His-Gly-His-His) in the linker region connecting its two catalytic domains senses pH and is involved in enzyme trafficking	Mus musculus

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Release 2023.1 (January 2023)