PTPRN2

PTPRN2

PTPRN2: Human protein tyrosine phosphatase, receptor type, N polypeptide 2
PDB Code: 2QEP
Description
PTPRN and PTPRN2 form a small subfamily of receptor protein tyrosine phosphatases (PTPs) that have been reported to be catalytically inactive enzymes. The lack of enzymatic activity has been associated with a number of substitutions of conserved amino acids within the PTP domain known to be critical for PTP activity. Specifically, the conserved proline in the WPD loop is changed into a tyrosine, and the obligatory alanine located close to the catalytic cysteine is an aspartic acid residue. Due to their lack of catalytic activity a function as phosphotyrosine recognition/binding module has been suggested. High expression levels of PTPRN2 have been detected in brain, pituitary, and pancreas as well as in insulinoma, glucagoma. Furthermore, PTPRN2 expression is upregulated by ghrelin, an endogenous ligand for growth hormone (GH) secretagogue (GHS) receptor.
Interestingly, PTPRNs have been identified as the precursors of 40- and 37-kDa insulin-dependent diabetes mellitus-specific major auto-antigens. Autoantibodies to PTPRN2 appear years before the development of clinical disease and are diagnostic and predictive markers. PTPRN2 knockout mice show mild glucose intolerance and impaired glucose-stimulated insulin secretion. However, knockout of the PTPRN2 gene in NOD mice (Nonobese diabetic), the most widely studied animal model for human type 1 diabetes, fail to prevent the development of cyclophosphamide-induced diabetes.
PTPRN2 has also been implicated in the development of the nervous system and regulation of exocytosis of insulin-containing secretory granules in pancreatic beta cells. In addition, PTPRN2 may regulate PTP activity of a number of receptor type PTPs through interaction with their D1 domains.

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