Signal sequences internal

Proteins targeted to the nucleus have an internal signal sequence that is not cleaved once the protein is successfully targeted. 

Recently sequences which can route proteins to peroxisomes have been identified (91). Firefly luciferase, a peroxisomal protein, contains a C-terminal serine-lysine-leucine which was shown to be critical for proper targeting. Indeed, most peroxisomal proteins analyzed thus far show similar sequences at their C-terminus a minority of proteins apparently utilize amino-terminal or internal signal sequences (92,93). 

Ouzzine, M., Magdalou, J., BurcheU, B. and Foumel-Gigleux, S. (1999) An internal signal sequence mediates the targeting and retention of the human UDP-glucuronosyltransferase 1A6 to the endoplasmic reticulum. J. Biol. Chem. 274 31401-31409. 

The above describes the major pathway of proteins destined for the mitochondrial matrix. However, certain proteins insert into the outer mitochoiidrial membrane facilitated by the TOM complex. Others stop in the intermembrane space, and some insert into the inner membrane. Yet others proceed into the matrix and then return to the inner membrane or intermembrane space. A number of proteins contain two signaling sequences—one to enter the mitochondrial matrix and the other to mediate subsequent relocation (eg, into the inner membrane). Certain mitochondrial proteins do not contain presequences (eg, cytochrome Cy which locates in the inter membrane space), and others contain internal presequences. Overall, proteins employ a variety of mechanisms and routes to attain their final destinations in mitochondria. 

Nilsson, I., Whitley, P., and von Heijne, G. (1994). The COOH-terminal ends of internal signal and signal-anchor sequences are positioned differently in the ER translocase. 

There should be no internal translation initiation signal (ATG) between a promoter sequence and a structural gene since an internal ATG sequence significantly reduces translation efficiency. The distance between the control regions (promoter and terminator) and the structural gene should not be too long. Otherwise a produced m-RNA would be less stable. 

Hunyady, L., Bor, M., Baukal, A. J., et al. 1995. A conserved NPLFY sequence contributes to agonist binding and signal transduction but is not an internalization signal for the type 1 angiotensin II receptor. J Biol Chem 270 16602-16609. 

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