SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the UBE2I gene.[5] It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe its function.
Four alternatively spliced transcript variants encoding the same protein have been found for this gene.[6]
The UBC9 protein encoded by the UBE2I gene constitutes a core machinery in the cell's sumoylation pathway. Sumoylation is a process in which a Small Ubiquitin-like MOdifier (SUMO) is covalently attached to other proteins in order to modify their behaviour. For example, sumoylation may affect a protein's localization in the cell, its ability to interact with other proteins or DNA.
UBC9 performs the third step in the sumoylation life cycle: the conjugation step. When SUMO protein precursors are first expressed, they first undergo a maturation step in which the four C-terminal amino acids are removed, revealing a di-glycine motif. In a second step, an E1 activating complex binds to SUMO at its di-glycine and passes it on to the E2 protein Ubc9, where it forms a thioester bond with a cysteine residue within Ubc9's catalytic pocket. The loaded Ubc9 is now ready to perform the sumoylation of its various target proteins (also called substrates). It recognizes a particular motif of amino acid residues in these substrates: A large hydrophobic residue, followed by a lysine, followed by a spacer, followed by an acidic residue. This motif is usually described in shorthand as ΨKxD/E. The central lysine within the substrate's recognition motif is inserted into the catalytic pocket. There the carboxyl terminus of SUMO's di-glycine forms a peptide bond with the ε-amino group of the lysine. This process can be assisted by an E3 ligase protein.
The sumoylation process is reversible. SENP proteases can remove SUMO from sumoylated proteins, freeing it to be used in further sumoylation reactions.
The protein UBC9 encoded by the UBE2I gene has been shown to be targeted by multiple viruses, including HIV and HPV. It has been hypothesized that these viruses hijack UBC9 to serve their own purposes.[7]
UBE2I has been shown to interact with:
PDB gallery
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1a3s: HUMAN UBC9
1kps: Structural Basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin conjugating enzyme Ubc9 and RanGAP1
1u9a: HUMAN UBIQUITIN-CONJUGATING ENZYME UBC9
1u9b: MURINE/HUMAN UBIQUITIN-CONJUGATING ENZYME UBC9
1z5s: Crystal structure of a complex between UBC9, SUMO-1, RANGAP1 and NUP358/RANBP2
2grn: Crystal Structure of human RanGAP1-Ubc9
2gro: Crystal Structure of human RanGAP1-Ubc9-N85Q
2grp: Crystal Structure of human RanGAP1-Ubc9-Y87A
2grq: Crystal Structure of human RanGAP1-Ubc9-D127A
2grr: Crystal Structure of human RanGAP1-Ubc9-D127S
2o25: Ubiquitin-Conjugating Enzyme E2-25 kDa Complexed With SUMO-1-Conjugating Enzyme UBC9
2pe6: Non-covalent complex between human SUMO-1 and human Ubc9
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Chaperones/ protein folding |
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Protein targeting |
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Ubiquitin (ubiquitylation) |
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Ubiquitin-like proteins (UBL) |
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