Search
receptor-type tyrosine-protein phosphatase epsilon; protein-tyrosine phosphatase epsilon; R-PTP-epsilon (PTPRE)
Function:
- isoform 1
- involved in signal transduction pathways & phosphoprotein network topology in erythrocytes
- may play a role in osteoclast formation & function
- isoform 2
- acts as a negative regulator of insulin receptor signaling in skeletal muscle
- regulates insulin-induced tyrosine phosphorylation of insulin receptor & insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B & glycogen synthase kinase-3 & insulin induced stimulation of glucose uptake (putative)
- interacts with GRB2 (putative)
- homodimer; can form oligomers
- dimerization is increased by oxidative stress & decreased by EGFR.
- isoform 1 & isoform 2
- act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production & degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 & LAT & mobilization of Ca+2 (putative)
- phosphorylated on Tyr by tyrosine kinase neu
- a catalytically active cytoplasmic form (p65) is produced by proteolytic cleavage of either isoform 1, isoform 2 or isoform 3
protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Structure:
- isoform 1: glycosylated, monomer
- the tyrosine-protein phosphatase 2 domain (D2) mediates dimerization
- the extreme N-terminal & C-terminal of the D2 domain act to inhibit dimerization & removal of these sequences increases dimerization & inhibits enzyme activity (putative)
- belongs to the protein-tyrosine phosphatase family receptor class 4 subfamily
- contains 2 tyrosine-protein phosphatase domains
Compartment:
- isoform 1: cell membrane; single-pass type 1 membrane protein
- isoform 2:
- cytoplasm, predominantly cytoplasmic
- a small fraction is also associated with nucleus & membrane
- insulin induces translocation to the membrane
- isoform 3: cytoplasm
Alternative initiation:
- alternative promoter usage
- named isoforms=3
Expression:
- expressed in giant cell tumor (osteoclastoma rich in multinucleated osteoclastic cells)
- up-regulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in HL-60 cells
General
glycoprotein
plasma membrane protein
tyrosine phosphatase, receptor type
Properties
SIZE: entity length = 700 aa
MW = 81 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: signal sequence {1-19}
N-glycosylation site {N23}
N-glycosylation site {N30}
transmembrane domain {47-69}
Tyrosine-protein phosphatase 1 {135-394}
MOTIF: binding site
SITE: 303-303
FOR-BINDING-OF: Substrate
Substrate binding {335-341}
cysteine residue {C335}
binding site
SITE: 379-379
FOR-BINDING-OF: Substrate
Tyrosine-protein phosphatase 2 {426-689}
MOTIF: cysteine residue {C630}
Tyr phosphorylation site {Y696}
STATE: active state
Database Correlations
OMIM 600926
UniProt P23469
Pfam PF00102
Entrez Gene 5791
Kegg hsa:5791
ENZYME 3.1.3.48
References
UniProt :accession P23469