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UBBA gene on chromosome 17p12-p11.2 that encodes a ubiquitin. Ubiquitins are either covalently attached to another protein, or free (unanchored). When covalently bound, ubiquitin is conjugated to target proteins, either as a monomer (monoubiquitin), a polymer linked to different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chain). Polyubiquitin chains attached to a target protein have different functions depending on the Lys residue of the ubiquitin attached. Linear polymer chains formed by attaching to the initiator Met lead to cell signalling. Free (unanchored) polyubiquitin is involved in activating protein kinases and in signalling.
Polyubiquitin Lys residues and roles
• Lys-6-linked—DNA repair.
• Lys-11-linked—ERAD (endoplasmic reticulum-associated degradation) and cell-cycle regulation.
• Lys-29-linked—Lysosomal degradation.
• Lys-33-linked—Kinase modification.
• Lys-48-linked—Protein degradation via the proteasome.
• Lys-63-linked—Endocytosis, DNA-damage response, signalling leading to activation of the transcription factor NF-kappaB.
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