First biological processes. Ubiquitin contains seven lysine residues, lysine-6,

First discovered by Gideon Goldstein in 1975,
ubiquitin is a small regulatory protein that exists in almost all eukaryotic
cells. It can be found in the nucleus, cytoplasm, and cell-surface membranes of
these eukaryotes. Ubiquitin has an amino acid sequence of 76 amino acids that
together aid in DNA repair, signal transduction and degradation of proteins.

Ubiquitin acts as a tag in the protein transport system to which proteins are
brought to the proteasome for digestion into short polypeptides or amino acids.

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This process is known as ubiquitination, which is the principal mechanism for
protein catabolism in mammalian cells throughout the animal kingdom.

Ubiquitin is a small molecule
that can attach itself to substrates within the human body to perform various
biological processes. Ubiquitin contains seven lysine residues, lysine-6,
lysine-11, lysine-27, lysine 29, lysine-33, lysine-48, and lysine-63. Depending
on the number of ubiquitin containing molecules bonded to which lysine residues,
monoubiquitin or polyubiquitin can be formed. Monoubiquitin, illustrated in
Figure 1, is a single ubiquitin molecule that is attached to one lysine residue
within the substrate.

Figure 1. 3D Structure of Mono-Ubiquitin.(PDB ID IUBQ) Ubiquitin structure shown in yellow cartoon
format. All lysine residues labeled and shown in stick format with nitrogen
groups highlighted in blue. Lysine-48 is highlighted in red. C-terminus and
N-terminus are labeled.

Polyquitination, on the other hand, is a chain of ubiquitin-ubiquitin linked
molecules attached to a specific lysine residue of the same substrate. Monoubiquitination
of a protein usually functions in the regulation of protein activation, signal
transduction, and DNA repair, whereas polyubiquitination primarily deals with
the degradation of proteins. Studies have shown that tagging of Lys-48 in
polyubiquitination mostly is utilized to target proteins for degradation by the
proteasome.

            Ubiquitination is an
ATP-dependent process orchestrated by three classes of enzymes known as E1, E2,
and E3. These enzymes function in the attachment of ubiquitin to proteins
destined for degradation. First, ubiquitin is activated by conjugation of E1 at
its C-terminus. Ubiquitin activating enzyme (E1), the initial enzyme in the ubiquitination
pathway, then allows for binding of ubiquitin to a ubiquitin conjugating enzyme
(E2) through the formation of a thiolester linkage. E2 then forms an isopeptide
bond with the C-terminus of ubiquitin and a lysine residue of the substrate
protein. Finally, through high specificity of the ubiquitin-protein ligase
(E3), the enzyme is able to recognize specific protein substrates and catalyze
the transfer of activated ubiquitin them.

Ubiquitin primarily
functions to target proteins for degradation, which plays a key role in the regulation
of the immune system. Therefore, deficiencies in ubiquitin can lead to certain diseases
or conditions within an individual.