Top Qs
Timeline
Chat
Perspective

NPEPPS

Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia

NPEPPS
Remove ads

Puromycin-sensitive amino peptidase also known as cytosol alanyl aminopeptidase or alanine aminopeptidase (AAP) (EC 3.4.11.14) is an enzyme that in humans is encoded by the NPEPPS gene.[5][6][7] It is used as a biomarker to detect damage to the kidneys, and that may be used to help diagnose certain kidney disorders. It is found at high levels in the urine when there are kidney problems.[8]

Quick Facts Identifiers, Aliases ...
Remove ads

Function

This gene encodes the puromycin-sensitive aminopeptidase, a zinc metallopeptidase which hydrolyzes amino acids from the N-terminus of its substrate. The protein has been localized to both the cytoplasm and to cellular membranes. This enzyme degrades enkephalins in the brain, and studies in mouse suggest that it is involved in proteolytic events regulating the cell cycle.[7] It has been identified as a novel modifier of TAU-induced neurodegeneration with neuroprotective effects via direct proteolysis of TAU protein.[9][10] The loss of NPEPPS function exacerbates neurodegeneration.[11]

Remove ads

Structure

Gene

The NPEPPS gene is located at chromosome 17q21, consisting of 25 exons and spanning 40 kb.

Protein

NPEPPS is a ubiquitous, 100 kDa, Zn2+ metallopeptidase highly expressed in the brain.[12] Two isozymes have been found and they are expressed differently in the nervous system.[13] Glu 309 is one of the active site glutamates, and its mutation could convert the enzyme into an inactive binding protein.[14]

Remove ads

Function

NPEPPS has been proposed to function in a variety of processes, including metabolism of neuropeptidase, regulation of the cell cycle, and hydrolysis of proteasomal products to amino acids.[15][16][17] NPEPPS is a major protease to digest SOD1, similar to its role in TAU-induced neurodegeneration.[10][18] NPEPPS is also reported to play a role in creating and destroying MHC class I-presented peptides and in limiting MHC class I Ag presentation in dendritic cells.[19]

Clinical significance

NPEPPS is induced in neurons expressing mutant huntingtin and is critical in preventing the accumulation of polyglutamine in normal cells. It has been reported as the major peptidase digesting polyglutamine sequences in neurodegenerative diseases, such as Huntington's disease.[20] It has been shown that elevation of NPEPPS activity in vivo could effectively block accumulation of hyperphosphorylated TAU protein and thus slow down the disease progression, suggesting increasing NPEPPS activity may be a feasible therapeutic approach to eliminate accumulation of toxic substrates, which are involved in neurodegenerative diseases.[21]

Remove ads

Interactions

References

Further reading

Loading related searches...

Wikiwand - on

Seamless Wikipedia browsing. On steroids.

Remove ads