Structural highlights
Function
PIR_HUMAN Possible transcriptional coregulator. May contribute to the regulation of cellular processes via its interaction with BCL3. May be required for efficient terminal myeloid maturation of hematopoietic cells. May play a role in the regulation of cell migration. May promote apoptosis when overexpressed. Has quercetin 2,3-dioxygenase activity (in vitro).[1] [2] [3] [4]
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
Pirin is a newly identified nuclear protein that interacts with the oncoprotein B-cell lymphoma 3-encoded (Bcl-3) and nuclear factor I (NFI). The crystal structure of human Pirin at 2.1-A resolution shows it to be a member of the functionally diverse cupin superfamily. The structure comprises two beta-barrel domains, with an Fe(II) cofactor bound within the cavity of the N-terminal domain. These findings suggest an enzymatic role for Pirin, most likely in biological redox reactions involving oxygen, and provide compelling evidence that Pirin requires the participation of the metal ion for its interaction with Bcl-3 to co-regulate the NF-kappaB transcription pathway and the interaction with NFI in DNA replication. Substitution of iron by heavy metals thus provides a novel pathway for these metals to directly influence gene transcription. The structure suggests an interesting new role of iron in biology and that Pirin may be involved in novel mechanisms of gene regulation.
Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor.,Pang H, Bartlam M, Zeng Q, Miyatake H, Hisano T, Miki K, Wong LL, Gao GF, Rao Z J Biol Chem. 2004 Jan 9;279(2):1491-8. Epub 2003 Oct 22. PMID:14573596[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wendler WM, Kremmer E, Forster R, Winnacker EL. Identification of pirin, a novel highly conserved nuclear protein. J Biol Chem. 1997 Mar 28;272(13):8482-9. PMID:9079676
- ↑ Gelbman BD, Heguy A, O'Connor TP, Zabner J, Crystal RG. Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis. Respir Res. 2007 Feb 8;8:10. PMID:17288615 doi:http://dx.doi.org/10.1186/1465-9921-8-10
- ↑ Licciulli S, Cambiaghi V, Scafetta G, Gruszka AM, Alcalay M. Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation. Leukemia. 2010 Feb;24(2):429-37. doi: 10.1038/leu.2009.247. Epub 2009 Dec 10. PMID:20010624 doi:http://dx.doi.org/10.1038/leu.2009.247
- ↑ Miyazaki I, Simizu S, Okumura H, Takagi S, Osada H. A small-molecule inhibitor shows that pirin regulates migration of melanoma cells. Nat Chem Biol. 2010 Sep;6(9):667-73. Epub 2010 Aug 15. PMID:20711196 doi:10.1038/nchembio.423
- ↑ Pang H, Bartlam M, Zeng Q, Miyatake H, Hisano T, Miki K, Wong LL, Gao GF, Rao Z. Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor. J Biol Chem. 2004 Jan 9;279(2):1491-8. Epub 2003 Oct 22. PMID:14573596 doi:http://dx.doi.org/10.1074/jbc.M310022200
