| Structural highlights
2k2d is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Related: | 2k2c |
| Gene: | RCHY1, ARNIP, CHIMP, PIRH2, RNF199, ZNF363 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN |
Function
[ZN363_HUMAN] Mediates E3-dependent ubiquitination and proteasomal degradation of target proteins, including p53/TP53, P73, HDAC1 and CDKN1B. Preferentially acts on tetrameric p53/TP53. Monoubiquitinates the translesion DNA polymerase POLH. Contributes to the regulation of the cell cycle progression. Increases AR transcription factor activity.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Pirh2 (p53-induced RING-H2 domain protein; also known as Rchy1) is an E3 ubiquitin ligase involved in a negative-feedback loop with p53. Using NMR spectroscopy, we show that Pirh2 is a unique cysteine-rich protein comprising three modular domains. The protein binds nine zinc ions using a variety of zinc coordination schemes, including a RING domain and a left-handed beta-spiral in which three zinc ions align three consecutive small beta-sheets in an interleaved fashion. We show that Pirh2-p53 interaction is dependent on the C-terminal zinc binding module of Pirh2, which binds to the tetramerization domain of p53. As a result, Pirh2 preferentially ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting that Pirh2 regulates protein turnover of the transcriptionally active form of p53.
Molecular basis of Pirh2-mediated p53 ubiquitylation.,Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH Nat Struct Mol Biol. 2008 Dec;15(12):1334-42. Epub 2008 Nov 30. PMID:19043414[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Corcoran CA, Montalbano J, Sun H, He Q, Huang Y, Sheikh MS. Identification and characterization of two novel isoforms of Pirh2 ubiquitin ligase that negatively regulate p53 independent of RING finger domains. J Biol Chem. 2009 Aug 14;284(33):21955-70. Epub 2009 May 29. PMID:19483087 doi:http://dx.doi.org/M109.024232
- ↑ Logan IR, Gaughan L, McCracken SR, Sapountzi V, Leung HY, Robson CN. Human PIRH2 enhances androgen receptor signaling through inhibition of histone deacetylase 1 and is overexpressed in prostate cancer. Mol Cell Biol. 2006 Sep;26(17):6502-10. PMID:16914734 doi:http://dx.doi.org/10.1128/MCB.00147-06
- ↑ Hattori T, Isobe T, Abe K, Kikuchi H, Kitagawa K, Oda T, Uchida C, Kitagawa M. Pirh2 promotes ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor p27Kip1. Cancer Res. 2007 Nov 15;67(22):10789-95. PMID:18006823 doi:http://dx.doi.org/10.1158/0008-5472.CAN-07-2033
- ↑ Maruyama S, Miyajima N, Bohgaki M, Tsukiyama T, Shigemura M, Nonomura K, Hatakeyama S. Ubiquitylation of epsilon-COP by PIRH2 and regulation of the secretion of PSA. Mol Cell Biochem. 2008 Jan;307(1-2):73-82. Epub 2007 Aug 25. PMID:17721809 doi:http://dx.doi.org/10.1007/s11010-007-9586-3
- ↑ Wu H, Zeinab RA, Flores ER, Leng RP. Pirh2, a ubiquitin E3 ligase, inhibits p73 transcriptional activity by promoting its ubiquitination. Mol Cancer Res. 2011 Dec;9(12):1780-90. doi: 10.1158/1541-7786.MCR-11-0157. Epub , 2011 Oct 12. PMID:21994467 doi:http://dx.doi.org/10.1158/1541-7786.MCR-11-0157
- ↑ Jung YS, Hakem A, Hakem R, Chen X. Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress translesion DNA synthesis. Mol Cell Biol. 2011 Oct;31(19):3997-4006. doi: 10.1128/MCB.05808-11. Epub 2011, Jul 26. PMID:21791603 doi:http://dx.doi.org/10.1128/MCB.05808-11
- ↑ Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH. Molecular basis of Pirh2-mediated p53 ubiquitylation. Nat Struct Mol Biol. 2008 Dec;15(12):1334-42. Epub 2008 Nov 30. PMID:19043414 doi:http://dx.doi.org/10.1038/nsmb.1521
- ↑ Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH. Molecular basis of Pirh2-mediated p53 ubiquitylation. Nat Struct Mol Biol. 2008 Dec;15(12):1334-42. Epub 2008 Nov 30. PMID:19043414 doi:http://dx.doi.org/10.1038/nsmb.1521
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