| Structural highlights
Function
[PTPRN_HUMAN] Implicated in neuroendocrine secretory processes. May be involved in processes specific for neurosecretory granules, such as their biogenesis, trafficking or regulated exocytosis or may have a general role in neuroendocrine functions. Seems to lack intrinsic enzyme activity. May play a role in the regulation of secretory granules via its interaction with SNTB2.[1] [2]
Publication Abstract from PubMed
IA-2 (insulinoma-associated protein 2) is a protein-tyrosine phosphatase receptor located in secretory granules of neuroendocrine cells. Initially, it attracted attention due to its involvement in the autoimmune response associated to diabetes. Later it was found that upon exocytosis, the cytoplasmic domain of IA-2 is cleaved and relocated to the nucleus, where it enhances the transcription of the insulin gene. A concerted functioning of the whole receptor is to be expected. However, very little is known about the structure and function of the transmembrane and extracellular domains of IA-2. To address this issue, we solved the x-ray structure of the mature ectodomain of IA-2 (meIA-2) to 1.30A resolution. The fold of meIA-2 is related to the SEA (sea urchin sperm protein, enterokinase, agrin)) domains of mucins, suggesting its participation in adhesive contacts to the extracellular matrix and providing clues on how this kind of molecule may associate and form homo- and heterodimers. Moreover, we discovered that meIA-2 is self-proteolyzed in vitro by reactive oxygen species, suggesting the possibility of a new shedding mechanism that might be significant in normal function or pathological processes. Knowledge of meIA-2 structure should facilitate the search of its possible ligands and molecular interactions.
Structure of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase IA-2.,Primo ME, Klinke S, Sica MP, Goldbaum FA, Jakoncic J, Poskus E, Ermacora MR J Biol Chem. 2008 Feb 22;283(8):4674-81. Epub 2007 Nov 29. PMID:18048354[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rabin DU, Pleasic SM, Shapiro JA, Yoo-Warren H, Oles J, Hicks JM, Goldstein DE, Rae PM. Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases. J Immunol. 1994 Mar 15;152(6):3183-8. PMID:8144912
- ↑ Solimena M, Dirkx R Jr, Hermel JM, Pleasic-Williams S, Shapiro JA, Caron L, Rabin DU. ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules. EMBO J. 1996 May 1;15(9):2102-14. PMID:8641276
- ↑ Primo ME, Klinke S, Sica MP, Goldbaum FA, Jakoncic J, Poskus E, Ermacora MR. Structure of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase IA-2. J Biol Chem. 2008 Feb 22;283(8):4674-81. Epub 2007 Nov 29. PMID:18048354 doi:10.1074/jbc.M708144200
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