When an itemframe is past 4 million blocks, you cannot place anything inside it, and if you try to place a block in it, it will place like a normal block and take up the whole voxel space. You cannot destroy the item frame with your fists or tools, but if you destroy the block it is on, it will pop off. When the x coord is past 4 million, you cannot place items on the west or east side, however the south and north side still work.
x > 4000000 , west/east affected
y> 4000000 , south north affected
x & y > 4000000 , all directions affected

You can get an item inside the itemframe but destroying the block it is on, and before it pops off, you place your block/item inside the frame and replace the block you broke. However it will not trigger a comparator, and you will not be able to turn it by right clicking.
This also happens in the nether. In multiplayer (vanilla) for me, even though only the x coord was past 4 million, the item frame was affected in all directions. I am not sure about the end or bukkit servers.