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.
Expression
[edit]Four alternatively spliced transcript variants encoding the same protein have been found for this gene.[6]
Function
[edit]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.
Clinical significance relevance
[edit]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]
Interactions
[edit]UBE2I has been shown to interact with:
- ATF2,[8]
- Androgen receptor,[9]
- BLMH,[10]
- DACH1,[11][12]
- DNMT3A,[13]
- DNMT3B,[14]
- DAXX,[15][16]
- ETS1,[17]
- FHIT,[18]
- IPO13,[19]
- MAP3K1[20] and
- MITF,[21]
- P53,[22][23][24][25]
- PIAS1,[26][27][28]
- PIAS2,[11][26]
- RAD51,[22][29]
- RANBP2,[30][31]
- RANGAP1,[15][30][32]
- SAE2,[15][30]
- SALL1,[33]
- SUMO1,[22][23][30][32]
- TCF3,[34]
- TNFRSF1A,[20]
- TOP1,[35] and
- WT1.[36]
Notes
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000103275 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015120 – Ensembl, May 2017
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- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ "Entrez Gene: UBE2I ubiquitin-conjugating enzyme E2I (UBC9 homolog, yeast)".
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- ^ Poukka H, Aarnisalo P, Karvonen U, Palvimo JJ, Jänne OA (July 1999). "Ubc9 interacts with the androgen receptor and activates receptor-dependent transcription". J. Biol. Chem. 274 (27): 19441–6. doi:10.1074/jbc.274.27.19441. PMID 10383460.
- ^ Koldamova RP, Lefterov IM, DiSabella MT, Lazo JS (Dec 1998). "An evolutionarily conserved cysteine protease, human bleomycin hydrolase, binds to the human homologue of ubiquitin-conjugating enzyme 9". Mol. Pharmacol. 54 (6): 954–61. doi:10.1124/mol.54.6.954. PMID 9855622.
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- ^ Kovalenko OV, Plug AW, Haaf T, Gonda DK, Ashley T, Ward DC, Radding CM, Golub EI (April 1996). "Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 recombination protein and localizes in synaptonemal complexes". Proc. Natl. Acad. Sci. U.S.A. 93 (7): 2958–63. Bibcode:1996PNAS...93.2958K. doi:10.1073/pnas.93.7.2958. PMC 39742. PMID 8610150.
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References
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- Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y (1998). "hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity". FEBS Lett. 425 (3): 431–5. doi:10.1016/S0014-5793(98)00287-7. PMID 9563508. S2CID 84816080.
- Koldamova RP, Lefterov IM, DiSabella MT, Lazo JS (1999). "An evolutionarily conserved cysteine protease, human bleomycin hydrolase, binds to the human homologue of ubiquitin-conjugating enzyme 9". Mol. Pharmacol. 54 (6): 954–61. doi:10.1124/mol.54.6.954. PMID 9855622.