Ubiquitin-conjugating enzymes, also known as E2 enzymes and more rarely as ''ubiquitin-carrier enzymes'', perform the second step in the

ubiquitination 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 ...

reaction that targets a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

for degradation via the

proteasome Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by whi ...

. The ubiquitination process

covalent A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...

ly attaches

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 ...

, a short protein of 76

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

s, to a

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated − ...

residue on the target protein. Once a protein has been tagged with one ubiquitin molecule, additional rounds of ubiquitination form a polyubiquitin chain that is recognized by the proteasome's 19S regulatory particle, triggering the ATP-dependent unfolding of the target protein that allows passage into the proteasome's 20S core particle, where

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

s degrade the target into short

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

fragments for recycling by the cell.

Relationships

A ubiquitin-activating enzyme, or E1, first activates the ubiquitin by covalently attaching the molecule to its

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate ( binding site) ...

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, some ...

residue. The activated ubiquitin is then transferred to an E2 cysteine. Once conjugated to ubiquitin, the E2 molecule binds one of several

ubiquitin ligase A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquit ...

s or E3s via a structurally conserved binding region. The E3 molecule is responsible for binding the target protein substrate and transferring the ubiquitin from the E2 cysteine to a lysine residue on the target protein. File:Ubiquitylation.png, Schematic diagram of the ubiquitylation system. A particular cell usually contains only a few types of E1 molecule, a greater diversity of E2s, and a very large variety of E3s. In humans, there are about 30 E2s which can bind with one of the 600+ E3s. The E3 molecules responsible for substrate identification and binding are thus the mechanisms of substrate specificity in proteasomal degradation. Each type of E2 can associate with many E3s. E2s can also be used to study protein folding mechanisms. Since the ubiquitylation system is shared across all organisms, studies can use modified E2 proteins in order to understand the overall system for how all organisms process proteins. There are also some proteins which can act as both and E2 and an E3 containing domains which cover both E2 and E3 functionality.

Isozymes

The following human genes encode ubiquitin-conjugating enzymes: *

UBE2A Ubiquitin-conjugating enzyme E2 A is a protein that in humans is encoded by the ''UBE2A'' gene. The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiqui ...

* UBE2B * UBE2C * UBE2D1, UBE2D2, UBE2D3, UBE2D4 (the latter putative) * UBE2E1, UBE2E2, UBE2E3 * UBE2F (putative) * UBE2G1, UBE2G2 *

UBE2H Ubiquitin-conjugating enzyme E2 H is a protein that in humans is encoded by the ''UBE2H'' gene. The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiqui ...

UBE2I SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the ''UBE2I'' gene. It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describ ...

* UBE2J1, UBE2J2 * UBE2K * UBE2L3,

UBE2L6 Ubiquitin/ISG15-conjugating enzyme E2 L6 is a protein that in humans is encoded by the ''UBE2L6'' gene. The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradati ...

; (

UBE2L1 UBE or Ube may refer to: * Ubiquitin-activating enzyme * Ube, Yamaguchi, a city in Japan * Uniform Bar Examination * Unilateral Biportal Endoscopy * Ube Industries, chemical company * Union bound estimate, a probability theory bound * Union of Bo ...

, UBE2L2, UBE2L4 are pseudogenes) * UBE2M * UBE2N * UBE2O * UBE2Q1, UBE2Q2 * UBE2R1 (CDC34), UBE2R2 * UBE2S *

UBE2T UBE or Ube may refer to: * Ubiquitin-activating enzyme * Ube, Yamaguchi, a city in Japan * Uniform Bar Examination * Unilateral Biportal Endoscopy * Ube Industries, chemical company * Union bound estimate, a probability theory bound * Union of Boo ...

(putative) * UBE2U (putative) * UBE2V1, UBE2V2 * UBE2W (putative) * UBE2Z * ATG3 * BIRC6 * UFC1

References

External links

* * Proteins Cell biology {{enzyme-stub

Relationships

Isozymes

See also

References

External links