Ubiquitin specific protease 4 (USP4) is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that cleaves
ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
from a number of protein substrates. Prior to the standardization of nomenclature USP4 was known as UNP, and was one of the first deubiquitinating enzymes to be identified in mammals.
In the mouse and human the USP4 protein is encoded by a gene containing 22
exons.
This protein is a member of
cysteine peptidase
Cysteine proteases, also known as thiol proteases, are hydrolase enzymes that degrade proteins. These proteases share a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic triad or dyad.
Discovered by Gopal Chund ...
family C19. As a
deubiquitinating enzyme
Deubiquitinating enzymes (DUBs), also known as deubiquitinating peptidases, deubiquitinating isopeptidases, deubiquitinases, ubiquitin proteases, ubiquitin hydrolases, ubiquitin isopeptidases, are a large group of proteases that cleave ubiquitin f ...
it is unusual in having the capacity to cleave ubiquitin-
proline bonds.
This property may reflect structural flexibility in the active site of the enzyme, and may explain its ability to cleave ubiquitin chains of various linkages. USP4 has substrates of important function in a number of cell signalling pathways, including the
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
,
TGF-β
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
,
Wnt/β-catenin,
p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
, and
spliceosome
A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs ( snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specif ...
pathways. Other substrates include the
adenosine A2A receptor
The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it.
Structure
This protein is a member of the G protein-coupled receptor (GPCR) family which possess seven transmembrane alph ...
and the Ro52 (
TRIM21
Tripartite motif-containing protein 21, also known as E3 ubiquitin-protein ligase TRIM21, is a protein that in humans is encoded by the ''TRIM21'' gene. Alternatively spliced transcript variants for this gene have been described but the full-length ...
) protein.
USP4 is a
nucleocytoplasmic shuttling protein Nuclear transport refers to the mechanisms by which molecules move across the nuclear membrane of a cell. The entry and exit of large molecules from the cell nucleus is tightly controlled by the nuclear pore complexes (NPCs). Although small molecul ...
that bears a functional
nuclear localization signal (NLS) 766QPQKKKK
772 and a
nuclear export signal (NES) 133VEVYLLELKL
142.
Those signals initiate the translocation of USP4 to the nucleus from the cytoplasm and vice versa, respectively. The proportion of cytoplasmic to nuclear USP4 pool varies depending on the cell type, the phase of cell cycle and the level of protein expression.
Interactions
USP4 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with the tumor suppressor
pRb protein and the pocket-related proteins
p107
The P107 was a World War II French half-track.
History
In the 1920s and 1930s Citroën developed a long line of half-tracks based on the Kégresse patent. In 1934, the company introduced its newest and more powerful P107 model as a successor t ...
and
p130.
References
Further reading
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External links
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