Proprotein

Like all neuropeptides, NT is synthesized as part of a larger precursor that also contains neuromedin N (NN), a 6 amino acid neurotensin-like peptide (Table 1). Pro-NT/NN is processed in the regulated secretory pathway of neuroendocrine cells by prohormone convertases PCI, PC2 and PC5-A that belong to a larger family of proprotein convertases. Due to differential cleavage specificity and tissue distribution of the convertases, pro-NT/NN processing gives rise to approximately a 1 1 and a 5 1 ratio of NT over NN content in the brain and gut, respectively. The peptides are stored in secretory vesicles and released from neuroendocrine cells in a Ca2+-dependent manner. NT and NN actions are terminated by desensitization of the... 

The maturation of proteins into their final structural state often involves the cleavage or formation (or both) of covalent bonds, a process termed posttranslational modification. Many polypeptides are initially synthesized as larger precursors, called proproteins. The extra polypeptide segments in these proproteins often serve as leader sequences that target a polypeptide... 

Many other peptides are synthesized as proproteins that require modifications before attaining biologic activity. Many of the posttranslational modifications involve the removal of amino terminal amino acid residues by specific aminopeptidases. Collagen, an abundant protein in the extracellular spaces of higher eukaryotes, is synthesized as procollagen. Three procol-... 

The MMPs are synthesized as preproproteins and are secreted as latent proproteins. Most MMPs share a common domain structure of a propeptide (about 80 amino acids) that has a conserved cysteine ligated to the catalytic zinc thus maintaining latency [10], a catalytic domain (about 180 amino acids), and a C-terminal domain (about 210 amino acids)... 

The term polyproteins is used for two different types of entity. The first refers to precursor polypeptides which are cleaved post-translationally into biologically active proteins or peptides of quite different functions. Examples of these include polyproteins of viruses and some prohormones of vertebrates (reviewed in Kennedy, 2000b). The other type is large proproteins which comprise tandem repetitions of identical or similar polypeptides that are post-translationally cleaved into multiple copies of biochemically similar functional entities. The nematode polyprotein allergens/antigens (NPAs) fall into this class (Fig. 16.1). 

Seidah, N. G. and Chretien, M. Proprotein and prohormone convertases a family of subtilases generating diverse bioactive polypeptides. Brain Res. 848 45-62,1999. 

SB 1 Family of endo- and exopeptidases (including proprotein convertases) Asp, His, Ser Parallel /3-sheet... 

Soon after it was shown that ubiquitin is conjugated to proteins, it was determined that this was a reversible process and deubiquitinating enzymes, or DUBs, could remove ubiquitin from ubiquitinated proteins [18, 19]. As the genes for ubiquitin and ubiquitin-like proteins were identified it became clear that all ubiquitin family members were synthesized as proproteins and processed to reveal the C-terminal glycylglycine of the active proteins [20]. Based on this information, DUBs were defined as proteases that cleave at the C-terminus of ubiquitin or ubiquitin-like proteins to reverse conjugation to target proteins and also process the proproteins. 

Kabisch UC, Grantzdorffer A, Schierhom A, et al. 1999. Identification of D-proline reductase from as a selenoenzyme and indications for a catalytically active pyruvoyl group derived from a cysteine residue by cleavage of a proprotein. J Biol Chem 274 8445-54. 

Many proteins are synthesized in inactive forms, termed proproteins. Insulin is created as an inactive single polypeptide chain and must be cleaved to create the active hormone. Many proteolytic enzymes are made as inactive precursors and must be cleaved to form enzymatically active molecules. 

Proteins that are destined to be secreted or to end up as transmembrane proteins are synthesized with an N-terminal signal peptide. Signal peptides are highly hydrophobic sequences of variable length. Proteins synthesized with signal peptides are termed preproteins. For example, insulin is a secreted protein. It is therefore synthesized as a preprotein. It is also synthesized in inactive form a proprotein. Insulin as initially synthesized is, in consequence, a preproprotein. 

Preproprotein a proprotein synthesized with the N-terminal signal peptide targeting it... 

Proprotein a protein that is s3uithesized in an inactive form. 

Inhibition of proprotein converases-1,-7 and furin by diterpenes of Andrographis paniculata and their succinoyl esters. Biochem J 338 107-113. 

The membranes of the Golgi apparatus contain receptor molecules that bind Man 6-P. They recognize lysosomal proproteins by this residue and bind them (3). With the help of clathrin, the receptors are concentrated locally. This allows the appropriate membrane sections to be pinched off and transported to the endolysosomes with the help of transport vesicles (4), from which primary lysosomes arise through maturation (5). Finally, the phosphate groups are removed from Man 6-P (6). 

This calcium-activated enzyme [EC 3.4.21.75] catalyzes the hydrolysis of peptide bonds in protein precursors that results in the release of mature proteins from their proproteins by hydrolysis of ArgXaaYaaArg—Zaa bonds, where Xaa can be any amino acid and Yaa is an arginyl or a lysyl residue. Albumin, complement component C3, and von Willebrand factor are thus released from their respective precursors. Furin is a member of the peptidase family S8. 

The tachykinins are sometimes thought to act as a unit in some areas of the nervous system, because (1) SP and NKA are produced from a common precursor, (2) the processing of the pre-proprotein involves the same proteolytic enzymes, (3) different tachykinins can be stored and co-released from the same neuron, (4) they are degraded by the same enzymes, and (5) different peptides may activate the same receptors (Hokfelt et al. 2001). However, the distribution and expression levels of the various PPTs and NK receptors are quite distinct in many brain regions. 

Proprotein. A protein that is made in an inactive form, so that it requires processing to become functional. 

Liu, G., Thomas, L., Warren, R. A., et al. (1997) Cytoskeletal protein ABP-280 directs the intracellular trafficking of furin and modulates proprotein processing in the endocytic pathway. J. Cell Biol. 139, 1719-1733. 

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