View source for Phosphatase Subfamily PTPN9

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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]:[[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_PTP|Family PTP]]: [[Phosphatase_Subfamily_PTPN9|Subfamily PTPN9]] (MEG2/PTPMEG2)

PTPN9/MEG2 is a metazoan subfamily functions in regulated secretory pathway. It has a characteristic accessory domain, a N-terminal Sec14p homology domain, which localizes it to secretory vesicles. 

===Evolution===
PTPN9 emerged in metazoan, usually one copy per genome.

===Domain ===
PTPN9 has two domains: a N-terminal domain homologous to yeast Sec14p and a C-terminal phosphatase domain <cite>Gu92</cite>.

The N-terminal Sec14p homology domain localizes the protein to secretory vesicles, by binding to phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P(3)) on secretory vesicle membranes <cite>Huynh03</cite> and/or mannose 6-phosphate receptor-interacting protein TIP47 and Arfaptin2 on vesicles <cite>Saito07</cite>.

===Functions===
PTPN9 is widely expressed in different tissues <cite>Gu92</cite> (also see [http://www.gtexportal.org/home/gene/PTPN9 GTEx]).

PTPN9/PTPMEG2 plays important role in regulated secretory pathway. It induces homotypic secretory vesicle fusion in cells. PTPN9/PTPMEG2 localizes to secretory vesicle membranes through its N-terminal Sec14p homolog domain binding to phosphatidylinositol-3,4,5-trisphosphate <cite>Huynh03</cite> and/or mannose 6-phosphate receptor-interacting protein TIP47 and Arfaptin2 on vesicles <cite>Saito07</cite>. It dephosphorylates N-ethylmaleimide-sensitive factor (NSF), a key regulator of vesicle fusion, at Tyr 83, which resulted in the local release of NSF from a tyrosine-phosphorylated, inactive state <cite>Huynh04</cite>.  

PTPN9/PTPMEG2 localizes to secondary and tertiary granules and secretory vesicles in neutrophils, and may regulate phagocytosis, an essential antimicrobial function in the innate immune response <cite>Kruger02</cite>.

PTPN9/PTPMEG2 directly interacts with STAT3 and mediates its dephosphorylation in the cytoplasm <cite>Su12</cite>.

PTPN9/PTPMEG2 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells <cite>Yuan10</cite>, and vascular endothelial growth factor receptor (perhaps on Tyr-1175) in endothelial cells <cite>Hao12</cite>.

PTPN9/PTPMEG2 also has an important role in the development of erythroid cells <cite>Xu03</cite>.

===References===
<biblio>
#Gu92 pmid=1557404
#Hao12 pmid=22763125
#Huynh03 pmid=14662869
#Huynh04 pmid=15322554
#Kruger02 pmid=11711529
#Saito07 pmid=17387180
#Su12 pmid=22394684
#Xu03 pmid=12920026
#Yuan10 pmid=20335174
</biblio>