Page last updated: 2024-10-24

protein K63-linked ubiquitination

Definition

Target type: biologicalprocess

A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 63 of the ubiquitin monomers, is added to a protein. K63-linked ubiquitination does not target the substrate protein for degradation, but is involved in several pathways, notably as a signal to promote error-free DNA postreplication repair. [GOC:mah, PMID:15556404]

K63-linked ubiquitination is a crucial post-translational modification that plays a critical role in diverse cellular processes. Unlike K48-linked ubiquitination, which primarily targets proteins for degradation by the proteasome, K63-linked ubiquitination does not lead to protein degradation. Instead, it serves as a versatile signaling mechanism involved in various cellular functions, including DNA repair, signal transduction, and immune responses.

The process of K63-linked ubiquitination begins with the activation of ubiquitin by the E1 ubiquitin-activating enzyme. The activated ubiquitin is then transferred to an E2 ubiquitin-conjugating enzyme, which facilitates the attachment of ubiquitin to a target protein. This process is further regulated by E3 ubiquitin ligases, which recognize specific target proteins and recruit the E2 enzyme to the site of ubiquitination.

K63-linked ubiquitination involves the formation of polyubiquitin chains, where ubiquitin monomers are linked together via lysine residue 63. This distinct linkage pattern results in a branched, non-degradative ubiquitin chain that acts as a scaffold for the recruitment of downstream effector proteins.

During DNA repair, K63-linked ubiquitination plays a critical role in the assembly of repair complexes. It facilitates the recruitment of DNA repair proteins, such as BRCA1 and 53BP1, to sites of DNA damage, enabling efficient DNA repair.

In signal transduction, K63-linked ubiquitination often acts as a signal amplifier. It enhances the activity of signaling proteins by promoting their interactions with other proteins, thereby amplifying the signal downstream.

K63-linked ubiquitination is also crucial for immune responses. It regulates the activation and signaling of immune receptors, such as Toll-like receptors (TLRs). It also plays a role in the formation of signaling complexes that mediate the production of inflammatory cytokines.

In summary, K63-linked ubiquitination is a complex and dynamic process that serves as a versatile signaling mechanism in various cellular processes. Its unique non-degradative nature allows it to regulate diverse cellular functions, including DNA repair, signal transduction, and immune responses.'
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Proteins (3)

ProteinDefinitionTaxonomy
E3 ubiquitin-protein ligase ZFP91An E3 ubiquitin-protein ligase ZFP91 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96JP5]Homo sapiens (human)
S-phase kinase-associated protein 2An S-phase kinase-associated protein 2 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
E3 ubiquitin-protein ligase XIAPA baculoviral IAP repeat-containing protein 4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P98170]Homo sapiens (human)

Compounds (15)

CompoundDefinitionClassesRoles
embelinembelin : A member of the class of dihydroxy-1,4-benzoquinones that is 2,5-dihydroxy-1,4-benzoquinone which is substituted by an undecyl group at position 3. Isolated from Lysimachia punctata and Embelia ribes, it exhibits antimicrobial, antineoplastic and inhibitory activity towards hepatitis C protease.

embelin: from Embelia fruit (Myrsinaceae)
dihydroxy-1,4-benzoquinonesantimicrobial agent;
antineoplastic agent;
hepatitis C protease inhibitor;
plant metabolite
phenylalanineL-phenylalanine : The L-enantiomer of phenylalanine.

phenylalanine : An aromatic amino acid that is alanine in which one of the methyl hydrogens is substituted by a phenyl group.

Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.
amino acid zwitterion;
erythrose 4-phosphate/phosphoenolpyruvate family amino acid;
L-alpha-amino acid;
phenylalanine;
proteinogenic amino acid
algal metabolite;
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
Escherichia coli metabolite;
human xenobiotic metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
8-(4-tolylsulfonylamino)quinoline8-(4-tolylsulfonylamino)quinoline: has diabetogenic properties; can be used for fluorometric determination of zinc; structure given in first sourcesulfonamide
pomalidomide3-aminophthalimidoglutarimide: structure in first sourcearomatic amine;
dicarboximide;
isoindoles;
piperidones
angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
nsc 680410NSC 680410: a bcr/abl kinase inhibitor; structure in first source
kaempferol7-hydroxyflavonol;
flavonols;
tetrahydroxyflavone
antibacterial agent;
geroprotector;
human blood serum metabolite;
human urinary metabolite;
human xenobiotic metabolite;
plant metabolite
kaempferol 3-o-rhamnosideafzelin : A glycosyloxyflavone that is kaempferol attached to an alpha-L-rhamnosyl residue at position 3 via a glycosidic linkage.

kaempferol 3-O-rhamnoside: from apple (Malus domestica) leaves; structure in first source
glycosyloxyflavone;
monosaccharide derivative;
trihydroxyflavone
anti-inflammatory agent;
antibacterial agent;
plant metabolite
lbw242LBW242: proapoptotic IAP inhibitor; low MW Smac (Second mitochondria-derived activator of caspases) mimetic; structure in first source
sm 164SM 164: a bivalent Smac mimetic with antineoplastic activity; structure in first sourcebenzenes;
organic heterobicyclic compound;
secondary carboxamide;
triazoles
antineoplastic agent;
apoptosis inducer;
radiosensitizing agent
lcl1611,3-thiazoles;
aromatic ketone;
L-alanine derivative;
monofluorobenzenes;
N-acylpyrrolidine
antineoplastic agent;
apoptosis inducer
at 406
gdc-0152GDC-0152: structure in first source
birinapantbirinapant: a Smac mimetic with antineoplastic activitydipeptide
nvp-cgm097NVP-CGM097: an MDM2 and HDM2 inhibitor; structure in first source
2-carboxyarabinitol 1-phosphate