3N4W

Crystal structure of an abridged SER to ALA mutant of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase ICA512/IA-2 at pH 7.5

Summary for 3N4W

• Entry DOI: 10.2210/pdb3n4w/pdb
• Related: 2QT7 3N0I
• Descriptor: Receptor-type tyrosine-protein phosphatase-like N, CALCIUM ION (3 entities in total)
• Functional Keywords: ia-2, ica-512, protein-tyrosine phosphatase, transmembrane protein, diabetes, autoimmunity, proteolysis, glycoprotein, receptor, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Membrane ; Single-pass type I membrane protein . ICA512-transmembrane fragment: Cytoplasmic vesicle, secretory vesicle membrane . ICA512-cleaved cytosolic fragment: Nucleus : Q16849
• Total number of polymer chains: 2
• Total formula weight: 19283.91

Authors

Primo, M.E.,Jakoncic, J.,Poskus, E.,Ermacora, M.R. (deposition date: 2010-05-23, release date: 2010-12-01, Last modification date: 2023-09-06)

Primary citation

Primo, M.E.,Klinke, S.,Sica, M.P.,Goldbaum, F.A.,Jakoncic, J.,Poskus, E.,Ermacora, M.R.
Structure of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase IA-2.
J.Biol.Chem., 283:4674-4681, 2008

PubMed Abstract: 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.

PubMed: 18048354
DOI: 10.1074/jbc.M708144200

Experimental method

X-RAY DIFFRACTION (1.45 Å)