Phosphatase Family PTP

Phosphatase Classification: Superfamily CC1: PTP

Classic PTP also called High Molecular Weight Protein Tyrosine Phosphatase (HMWPTP) in the SCOP database. Compare to DSP and PTEN family, it has an extension to the beta-sheet of 3 antiparallel strands before strand 4. Based on the presence of transmembrane region, this family can be divided into two types, transmembrane receptor PTPs and intracellular non-receptor PTPs.

Tandem Phosphatase Domain receptor PTPs

PTPRA

PTPRA and PTPRE.

PTPRC

PTPRC (CD45)

PTPRD

PTPRD, PTPRF, PTPRS

PTPRG

PTPRG, PTPRZ1

PTPRK

PTPRK, PTPRM, PTPRT, PTPRU

PTPRB

PTPRB, PTPRH, PTPRJ, PTPRO, PTPRQ

PTPN5

PTPN5

The N5 subfamily has three human members: N5, N7 and RR, (also called STEP, HEPTP and PTP-SL, respectively). A 16-residue KIM motif distinguishes them from other PTPs. N5 and RR have predicted transmembrane regions, as does the single copy in sponge. However, the single Drosophila copy has no predicted transmembrane region. N5 members selectively bind to ERK1/2 and p38 (other substrates have been reported, too). ERK1/2 can phosphorylate Thr residue of KIM. PKA phoshorylates Ser23 of the KIM and reduces the affinity for ERK1/2 and p38. This subfamily is metazoan-specific.

PTPN6

PTPN6, PTPN11

PTPN3

PTPN3

PTPN3, PTPN4

PTPN14

PTPN14, PTPN21. Two copies in human, PTPN14 and PTPN21. Their substrates are beta-catenin, and BMX of Tec kinase family, respectively. The phosphatase is conserved from sponge to human and the kinase is conserved from Monosiga to human. The phosphatase and kinase lost together in C. elegans.

PTPN13

PTPN13

PTPN13. Single copy in each organism. It has FERM and multiple PDZ domains in addition to phosphatase domain. It is conserved from Monosiga to human but lost in sponge, C. elegans and fly. Mice homozygous for its null allele exhibit abnormal T-helper cell differentiation. Its presence in Monosiga and absence is various organisms suggests its basal but non-essential function.

PTPN20

PTPN20. It is vertebrate specific. It has two copies in human, PTPN20A and PTPN20B. Their sequences are almost identical. Their function is unclear.

PTPN1

PTPN1

Two copies in human, PTPN1 (PTP1B) and PTPN2. It contains a single phosphatase domain. They dephoshorylate kinases of various families, including Insulin receptor kinase (InsR), epidermal growth factor receptor kinase (EGFR), JAK (JAK2 and TYK2). The phosphatase emerged later than the related kinases. The phosphatase first emerged in Trichoplax. EGFR is conserved from sponge to human but lost in Trichoplax, and InsR is conserved from Trichoplax to human.

PTPN23

See the web page for PTPN23.

PTPN9

The N9 subfamily consists of one gene in humans (PTPN9/PTP-MEG2), and homologs throughout metazoans. The protein has a Sec14 domain N-teminal of the PTP domain, which targets the protein to the membrane of secretory vesicles (PMID: 15322554), where it regulates vesicle fusion. PTPN9 desphosphorylates and activates NSF (N-ethylmaleimide-sensitive factor), a regulator of vesicle fusion.

The human gene is also implicated in signaling between insulin receptor (InsR) and the FoxO transcription factor (PMID: 16679294).

PTPN12

Three copies in human, PTPN12, PTPN18 and PTPN22. They have a phosphatase domain and C-terminal PEST motif involved in protein degradation. PTPN12 has various substrates, including tyrosine kinases cABL of Abl kinase family and PYK2 of FAK kinase family. PTPN18 can dephoshorylate ErbB2 of EGFR kinase family. The N12 subfamily is found from Monosiga to human, as is the Abl kinase family. The other two kinase families FAK and EGFR are conserved from sponge to human.