Phosphatase Subfamily PTPN1

Phosphatase Classification: Fold CC1:Superfamily CC1: Family PTP: Subfamily PTPN1

The PTPN1 subfamily dephoshorylates kinases of various families, including Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2).

Evolution

PTPN1 subfamily emerged in animals, as it is found in most if not all eumetazoa, Porifera (e.g. sponge) and Placozoa (e.g. Trichoplax), but absent from Choanoflagellata (e.g. Monosiga) (for the phylogeny of animal at here). In human, there are two copies: PTPN1 (PTP1B) and PTPN2 (TCPTP). The two copies can be traced back to the time when vertebrates emerged. The orthologs for each of them are found in most vertebrates from fish to primates, and there is a single copy in non-vertebrate metazoa.

Domain

The PTPN1 subfamily has a single structural domain, phosphatase domain.

Functions

The PTPN1 subfamily has various functions [1, 2, 3, 4]. It dephoshorylates kinases of various families, such as Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2):

• BRK. PTPN1 (PTP1B) inhibited BRK, a member of SRM subfamily, SRC family, by directly dephosphorylating the Tyr-342 autophosphorylation site [5].

• STAT3. PTPN2 (TCPTP) interacts with, dephosphorylates and inactivates STAT3. The activity is enhanced by STAT3-Interacting Protein As a Repressor (SIPAR) [6].

Miscellaneous functions and regulatory mechanisms

• Human PTPN1 (PTPB1) is regulated via glutathionylation of cysteine at the catalytic motif Cx5R [7].
• Human PTPN1 (PTPB1) plays a key role in regulating dendritic cell maturation, migration and T cell activation [8].

References

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