Phosphatase Family PTP
Phosphatase Classification: Superfamily CC1: PTP
The Protein Tyrosine Phosphatase Family (PTP) is the major tyrosine-specific family of phosphatases, present throughout animals and consisting of both transmembrane receptors (rPTPs) and non-receptor phosphatases (nrPTP), in several distinct subfamilies. This subfamily is known as High Molecular Weight Protein Tyrosine Phosphatase (HMWPTP) in the SCOP database. Compared to the related dual-specific DSP and PTEN family, it has an extension to the beta-sheet of 3 antiparallel strands before strand 4.
Contents
[hide]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
PTPRN
PTPRN and PTPRN2
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, 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. 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
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.