Application | Comment | Organism |
---|---|---|
diagnostics | decreased PTPN12 protein level is associated with poor prognosis of several types of cancers | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
gene PTPN12, recombinant expression of wild-type and mutant GST-tagged enzymes in Escherichia coli | Homo sapiens |
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 | 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 | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
[a protein]-tyrosine phosphate + H2O | Homo sapiens | - |
[a protein]-tyrosine + phosphate | - |
? | |
[epidermal growth factor receptor 2]-tyrosine phosphate + H2O | Homo sapiens | dephosphorylation of epidermal growth factor receptor 2 (HER2)-pY1196 site | [epidermal growth factor receptor 2]-tyrosine + phosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q05209 | - |
- |
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 (Comment) | Organism |
---|---|
recombinant wild-type and mutant GST-tagged enzymes from Escherichia coli by glutathione affinity chromatography | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
MDA-MB-231 cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
4-nitrophenyl phosphate + H2O | - |
Homo sapiens | 4-nitrophenol + phosphate | - |
? | |
ENPE(pY)LGLD + H2O | dephosphorylation at Tyr1248 | Homo sapiens | ENPEYLGLD + phosphate | - |
? | |
ENPE(pY)LTPQ + H2O | dephosphorylation at Tyr1196 | Homo sapiens | ENPEYLTPQ + phosphate | - |
? | |
FDNL(pY)2WDQD + H2O | dephosphorylation at Tyr1221/1222 | Homo sapiens | FDNLYYWDQD + 2 phosphate | - |
? | |
PLQR(pY)SEDP + H2O | dephosphorylation at Tyr1112 | Homo sapiens | PLQRYSEDP + phosphate | - |
? | |
[a protein]-tyrosine phosphate + H2O | - |
Homo sapiens | [a protein]-tyrosine + phosphate | - |
? | |
[epidermal growth factor receptor 2]-tyrosine phosphate + H2O | dephosphorylation of epidermal growth factor receptor 2 (HER2)-pY1196 site | Homo sapiens | [epidermal growth factor receptor 2]-tyrosine + phosphate | - |
? | |
[FAK]-tyrosine phosphate + H2O | dephosphorylation at Tyr397 | Homo sapiens | [FAK]-tyrosine + phosphate | - |
? | |
[HER2]-tyrosine phosphate + H2O | dephosphorylation at Tyr1112, Tyr1196, Tyr1221, Tyr1222, and Tyr1248 | Homo sapiens | [HER2]-tyrosine + phosphate | - |
? | |
[p130Cas]-tyrosine phosphate + H2O | dephosphorylation at Tyr165 | Homo sapiens | [p130Cas]-tyrosine + phosphate | - |
? | |
[p190RhoGAP]-tyrosine phosphate + H2O | dephosphorylation at Tyr1105 | Homo sapiens | [p190RhoGAP]-tyrosine + phosphate | - |
? | |
[paxillin]-tyrosine phosphate + H2O | dephosphorylation at Tyr118 | Homo sapiens | [paxillin]-tyrosine + phosphate | - |
? | |
[SRC]-tyrosine phosphate + H2O | dephosphorylation at Tyr416 | Homo sapiens | [SRC]-tyrosine + phosphate | - |
? | |
[VAV2]-tyrosine phosphate + H2O | dephosphorylation at Tyr172 | Homo sapiens | [VAV2]-tyrosine + phosphate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
More | cf. EC 3.1.3.16 | Homo sapiens |
protein tyrosine phosphatase N12 | - |
Homo sapiens |
PTPN12 | - |
Homo sapiens |
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 Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00052 | - |
PLQR(pY)SEDP | recombinant mutant S39E, pH and temperature not specified in the publication | Homo sapiens | |
0.00112 | - |
ENPE(pY)LGLD | recombinant mutant S39E, pH and temperature not specified in the publication | Homo sapiens | |
0.00115 | - |
ENPE(pY)LTPQ | recombinant mutant S39E, pH and temperature not specified in the publication | Homo sapiens | |
0.00137 | - |
PLQR(pY)SEDP | recombinant mutant S19A, pH and temperature not specified in the publication | Homo sapiens | |
0.00139 | - |
PLQR(pY)SEDP | recombinant mutant S19E, pH and temperature not specified in the publication | Homo sapiens | |
0.00142 | - |
PLQR(pY)SEDP | recombinant wild-type enzyme, pH and temperature not specified in the publication | Homo sapiens | |
0.00187 | - |
FDNL(pY)2WDQD | recombinant mutant S39E, pH and temperature not specified in the publication | Homo sapiens | |
0.00255 | - |
ENPE(pY)LGLD | recombinant mutant S19A, pH and temperature not specified in the publication | Homo sapiens | |
0.00257 | - |
ENPE(pY)LTPQ | recombinant mutant S19E, pH and temperature not specified in the publication | Homo sapiens | |
0.00259 | - |
ENPE(pY)LGLD | recombinant mutant S19E, pH and temperature not specified in the publication | Homo sapiens | |
0.00262 | - |
ENPE(pY)LTPQ | recombinant wild-type enzyme, pH and temperature not specified in the publication | Homo sapiens | |
0.00269 | - |
ENPE(pY)LGLD | recombinant wild-type enzyme, pH and temperature not specified in the publication | Homo sapiens | |
0.00271 | - |
ENPE(pY)LTPQ | recombinant mutant S19A, pH and temperature not specified in the publication | Homo sapiens | |
0.00389 | - |
FDNL(pY)2WDQD | recombinant mutant S19A, pH and temperature not specified in the publication | Homo sapiens | |
0.00393 | - |
FDNL(pY)2WDQD | recombinant mutant S19E, pH and temperature not specified in the publication | Homo sapiens | |
0.00397 | - |
FDNL(pY)2WDQD | recombinant wild-type enzyme, pH and temperature not specified in the publication | Homo sapiens | |
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 |