PTPRN Proteins

Protein Information

IA-2 (insulinoma-associated protein 2, ICA512, PTPRN) is a member of the transmembrane protein tyrosine phosphatase (PTP) family located in secretory granules of neuroendocrine cells. The IA-2 protein is 979 amino acids in length and consists of a luminal domain, transmembrane domain, and cytoplasmic domain. Although a member of the PTP family, IA-2 lacks phosphatase activity with known substrates due to amino acid substitutions at critical sites in its PTP domain. Two paralog RPTPs, IA-2 and IA-2beta were identified as major autoantigens in type-1 diabetes mellitus. On granule exocytosis, the IA-2 cytoplasmic domain is cleaved and the resulting cytosolic fragment moves into the nucleus where it enhances the levels of phosphorylated STAT5 and STAT3, thereby inducing insulin gene transcription and granule biogenesis. IA-2 signaling enhances pancreatic beta-cell proliferation by regulating cyclins D through STATs.

Synonyms

105 kDa islet cell antigen; BEM-3; Brain-enriched membrane-associated protein tyrosine phosphatase; IA2; IA-2; IA-2/PTP; ICA 512; ICA105; ICA3; ICA512; ICA512-CCF; ICA512-cleaved cytosolic fragment; ICA512-N-terminal fragment; ICA512-NTF; ICA512-TMF; ICA512-transmembrane fragment; islet cell antigen 2; islet cell antigen 512; Islet cell autoantigen 3; mIA-A; mKIAA4064; protein tyrosine phosphatase, receptor type N; protein tyrosine phosphatase, receptor type, N; protein tyrosine phosphatase, receptor-type, N; protein tyrosine phosphatase-like N; PTP IA-2; PTPLP; Ptprn; Receptor-type tyrosine-protein phosphatase-like N; R-PTP-N