Literature summary for 3.1.3.16 extracted from

Li, H.; Yang, D.; Ning, S.; Xu, Y.; Yang, F.; Yin, R.; Feng, T.; Han, S.; Guo, L.; Zhang, P.; Qu, W.; Guo, R.; Song, C.; Xiao, P.; Zhou, C.; Xu, Z.; Sun, J.P.; Yu, X.
Switching of the substrate specificity of protein tyrosine phosphatase N12 by cyclin-dependent kinase 2 phosphorylation orchestrating 2 oncogenic pathways (2018), FASEB J., 32, 73-82 .

Search for more literature for 3.1.3.16

Application

Application	Comment	Organism
diagnostics	decreased PTPN12 protein level is associated with poor prognosis of several types of cancers	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
gene PTPN12, recombinant expression of wild-type and mutant GST-tagged enzymes in Escherichia coli	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
S19A	site-directed mutagenesis, mutant PTPN12-S19A is efficient in inhibiting EGF-induced cell migration, the mutant does not produce significant differences in PTPN12's recognition of all HER2-phospho-peptides compared to wild-type PTPN12	Homo sapiens
S19E	site-directed mutagenesis, mutant PTPN12-S19E is less efficient in inhibiting EGF-induced cell migration, the mutant does not produce significant differences in PTPN12's recognition of all HER2-phospho-peptides compared to wild-type PTPN12	Homo sapiens
S39E	site-directed mutagenesis, the mutant impairs activity of PTPN12 toward all HER2-phosphopeptide by 2-3fold compared to wild-type, mutation S39E decreases the activity of PTPN12 toward all tested HER2 pY sites in vitro, the mutation directly affected the interaction between the PTPN12 and the residues flanking the pY of the HER2 phosphorylation sites	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
additional information	phosphorylation of PTPN12 at Ser19 changes its substrate interface, and by doing so, selectively decreases its activity toward the human epidermal growth factor receptor 2 (HER2)-pY1196 site, but not other HER2 phosphorylation sites or other known PTPN12 substrates, such as SRC, paxillin, PAK1,VAV2, p130Cas, FAK, and p190RhoGAP	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
[a protein]-serine/threonine phosphate + H2O	Homo sapiens	-	[a protein]-serine/threonine + phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q05209	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
phosphoprotein	phosphorylation of PTPN12 at Ser19 changes its substrate interface, and by doing so, selectively decreases its activity toward the human epidermal growth factor receptor 2 (HER2)-pY1196 site, but not other HER2 phosphorylation sites or other known PTPN12 substrates. Phosphorylation of Ser19 by CDK2 specifically increases EGF-induced HER2-pY1196 and PAK1-pT423 phosphorylation. Phosphorylation of PTPN12 byCDK2 impairs recruitment of the serine/threonine-protein kinase 1 (PAK1) to HER2, resulting in the blockade of the HER2-pY1196-PAK1-T423 signaling pathway, thus increases tumor cell motility	Homo sapiens

Purification (Commentary)

Purification (Comment)	Organism
recombinant wild-type and mutant GST-tagged enzymes from Escherichia coli by glutathione affinity chromatography	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
MDA-MB-231 cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
4-nitrophenyl phosphate + H2O	-	Homo sapiens	4-nitrophenol + phosphate	-	?
[a protein]-serine/threonine phosphate + H2O	-	Homo sapiens	[a protein]-serine/threonine + phosphate	-	?
[PAK1]-serine phosphate + H2O	dephosphorylation at Ser144	Homo sapiens	[PAK1]-serine + phosphate	-	?
[VAV2]-threonine phosphate + H2O	dephosphorylation at Thr423	Homo sapiens	[VAV2]-threonine + phosphate	-	?

Synonyms

Synonyms	Comment	Organism
More	cf. EC 3.1.3.48	Homo sapiens
PTPN12	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	phosphorylation of PTPN12 at Ser19 by CDK2 impairs recruitment of the serine/threonine-protein kinase 1 (PAK1) to HER2, resulting in the blockade of the HER2-pY1196-PAK1-T423 signaling pathway, thus increases tumor cell motility. Decreased PTPN12 protein level is associated with poor prognosis of several types of cancers. Phosphorylation of Ser19 by CDK2 specifically increases EGF-induced HER2-pY1196 and PAK1-pT423 phosphorylation	Homo sapiens
metabolism	a CDK2-mediated phosphorylation-based substrate recognition mechanism of PTPN12 orchestrated signaling crosstalk between the oncogenic CDK2 and HER2 pathways	Homo sapiens
physiological function	the protein tyrosine phosphatase nonreceptor type 12 (PTPN12) is a multifunctional protein. A CDK2-mediated phosphorylation-based substrate recognition mechanism of PTPN12 orchestrated signaling crosstalk between the oncogenic CDK2 and HER2 pathways	Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism	Structure
0.452	-	4-nitrophenyl phosphate	recombinant mutant S39E, pH and temperature not specified in the publication	Homo sapiens
0.51	-	4-nitrophenyl phosphate	recombinant mutant S19A, pH and temperature not specified in the publication	Homo sapiens
0.52	-	4-nitrophenyl phosphate	recombinant wild-type enzyme, pH and temperature not specified in the publication	Homo sapiens
0.532	-	4-nitrophenyl phosphate	recombinant mutant S19E, pH and temperature not specified in the publication	Homo sapiens

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Release 2023.1 (January 2023)