| Structural highlights
Function
[ARI1_HUMAN] E3 ubiquitin-protein ligase, which catalyzes polyubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3. May play a role in protein translation by mediating polyubiquitination of EIF4E2, leading to its subsequent degradation.[1] [2] [3] [UB2L3_HUMAN] Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PARK2 and ARIH1, that function like function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down-regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis.[4] [5] [6] [7] [8] [9] [10]
Publication Abstract from PubMed
RING-between-RING (RBR) E3s contain RING1 domains that are structurally similar yet mechanistically distinct from canonical RING domains. Both types of E3 bind E2 approximately ubiquitin (E2 approximately Ub) via their RINGs but canonical RING E3s promote closed E2 approximately Ub conformations required for direct Ub transfer from the E2 to substrate, while RBR RING1s promote open E2 approximately Ub to favor Ub transfer to the E3 active site. This different RING/E2 approximately Ub conformation determines its direct target, which for canonical RING E3s is typically a substrate or substrate-linked Ub, but is the E3 active-site cysteine in the case of RBR-type E3s. Here we show that a short extension of HHARI RING1, namely Zn2+-loop II, not present in any RING E3s, acts as a steric wedge to disrupt closed E2 approximately Ub, providing a structural explanation for the distinctive RING1-dependent conformational restriction mechanism utilized by RBR E3s.
Structural Studies of HHARI/UbcH7 approximately Ub Reveal Unique E2 approximately Ub Conformational Restriction by RBR RING1.,Dove KK, Olszewski JL, Martino L, Duda DM, Wu XS, Miller DJ, Reiter KH, Rittinger K, Schulman BA, Klevit RE Structure. 2017 Jun 6;25(6):890-900.e5. doi: 10.1016/j.str.2017.04.013. Epub 2017, May 25. PMID:28552575[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tan NG, Ardley HC, Scott GB, Rose SA, Markham AF, Robinson PA. Human homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E homologous protein, 4EHP. FEBS Lett. 2003 Nov 20;554(3):501-4. PMID:14623119
- ↑ Wenzel DM, Lissounov A, Brzovic PS, Klevit RE. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature. 2011 Jun 2;474(7349):105-8. doi: 10.1038/nature09966. Epub 2011 May 1. PMID:21532592 doi:10.1038/nature09966
- ↑ Capili AD, Edghill EL, Wu K, Borden KL. Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif reveals a novel zinc-binding domain distinct from a RING. J Mol Biol. 2004 Jul 23;340(5):1117-29. PMID:15236971 doi:10.1016/j.jmb.2004.05.035
- ↑ Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000 Jul;25(3):302-5. PMID:10888878 doi:10.1038/77060
- ↑ Verma S, Ismail A, Gao X, Fu G, Li X, O'Malley BW, Nawaz Z. The ubiquitin-conjugating enzyme UBCH7 acts as a coactivator for steroid hormone receptors. Mol Cell Biol. 2004 Oct;24(19):8716-26. PMID:15367689 doi:10.1128/MCB.24.19.8716-8726.2004
- ↑ Garside H, Waters C, Berry A, Rice L, Ardley HC, White A, Robinson PA, Ray D. UbcH7 interacts with the glucocorticoid receptor and mediates receptor autoregulation. J Endocrinol. 2006 Sep;190(3):621-9. PMID:17003263 doi:10.1677/joe.1.06799
- ↑ Marteijn JA, van der Meer LT, Smit JJ, Noordermeer SM, Wissink W, Jansen P, Swarts HG, Hibbert RG, de Witte T, Sixma TK, Jansen JH, van der Reijden BA. The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 interacting domains. Leukemia. 2009 Aug;23(8):1480-9. Epub 2009 Apr 2. PMID:19340006 doi:leu200957
- ↑ Whitcomb EA, Dudek EJ, Liu Q, Taylor A. Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme H7. Mol Biol Cell. 2009 Jan;20(1):1-9. doi: 10.1091/mbc.E08-01-0036. Epub 2008 Oct, 22. PMID:18946090 doi:10.1091/mbc.E08-01-0036
- ↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
- ↑ Wenzel DM, Lissounov A, Brzovic PS, Klevit RE. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature. 2011 Jun 2;474(7349):105-8. doi: 10.1038/nature09966. Epub 2011 May 1. PMID:21532592 doi:10.1038/nature09966
- ↑ Dove KK, Olszewski JL, Martino L, Duda DM, Wu XS, Miller DJ, Reiter KH, Rittinger K, Schulman BA, Klevit RE. Structural Studies of HHARI/UbcH7 approximately Ub Reveal Unique E2 approximately Ub Conformational Restriction by RBR RING1. Structure. 2017 Jun 6;25(6):890-900.e5. doi: 10.1016/j.str.2017.04.013. Epub 2017, May 25. PMID:28552575 doi:http://dx.doi.org/10.1016/j.str.2017.04.013
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