| Structural highlights
2ilr is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | FANCE (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[FANCE_HUMAN] Defects in FANCE are a cause of Fanconi anemia complementation group E (FANCE) [MIM:600901]. A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.[1]
Function
[FANCE_HUMAN] As part of the Fanconi anemia (FA) complex functions in DNA cross-links repair. Required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2.[2] [3]
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
Fanconi Anaemia (FA) is a cancer predisposition disorder characterized by spontaneous chromosome breakage and high cellular sensitivity to genotoxic agents. In response to DNA damage, a multi-subunit assembly of FA proteins, the FA core complex, monoubiquitinates the downstream FANCD2 protein. The FANCE protein plays an essential role in the FA process of DNA repair as the FANCD2-binding component of the FA core complex. Here we report a crystallographic and biological study of human FANCE. The first structure of a FA protein reveals the presence of a repeated helical motif that provides a template for the structural rationalization of other proteins defective in Fanconi Anaemia. The portion of FANCE defined by our crystallographic analysis is sufficient for interaction with FANCD2, yielding structural information into the mode of FANCD2 recruitment to the FA core complex. Disease-associated mutations disrupt the FANCE-FANCD2 interaction, providing structural insight into the molecular mechanisms of FA pathogenesis.
Insights into Fanconi Anaemia from the structure of human FANCE.,Nookala RK, Hussain S, Pellegrini L Nucleic Acids Res. 2007;35(5):1638-48. Epub 2007 Feb 18. PMID:17308347[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ de Winter JP, Leveille F, van Berkel CG, Rooimans MA, van Der Weel L, Steltenpool J, Demuth I, Morgan NV, Alon N, Bosnoyan-Collins L, Lightfoot J, Leegwater PA, Waisfisz Q, Komatsu K, Arwert F, Pronk JC, Mathew CG, Digweed M, Buchwald M, Joenje H. Isolation of a cDNA representing the Fanconi anemia complementation group E gene. Am J Hum Genet. 2000 Nov;67(5):1306-8. Epub 2000 Sep 19. PMID:11001585 doi:S0002-9297(07)62959-0
- ↑ Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ. FANCE: the link between Fanconi anaemia complex assembly and activity. EMBO J. 2002 Jul 1;21(13):3414-23. PMID:12093742 doi:10.1093/emboj/cdf355
- ↑ Wang X, Kennedy RD, Ray K, Stuckert P, Ellenberger T, D'Andrea AD. Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway. Mol Cell Biol. 2007 Apr;27(8):3098-108. Epub 2007 Feb 12. PMID:17296736 doi:10.1128/MCB.02357-06
- ↑ Nookala RK, Hussain S, Pellegrini L. Insights into Fanconi Anaemia from the structure of human FANCE. Nucleic Acids Res. 2007;35(5):1638-48. Epub 2007 Feb 18. PMID:17308347 doi:10.1093/nar/gkm033
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