Protein DomainsWhat are protein domains?Protein domains are conserved spans of amino acids that have a structural or functional role within a protein. Domains are the functional units of proteins that together contribute to the overall role of the protein. The presence of particular domains within a protein can help to characterize proteins by comparison with other proteins with similar domain architecture [1].
Identifying protein domainsTo identify domains within the FANCL protein Pfam and SMART, two protein sequence analysis and classification databases, were used [2,3]. First using Pfam, a WD-3 repeat and c-terminal RING finger domain were recognized between position 8 and 300 and 308 and 376, respectively. Following up with SMART, only one domain was recognized, a RING domain between 312 and 367. Below are the visualizations of these domains identifications within the FANCL protein.
Following initial identification of protein domains within the human FANCL protein, InterPro, another sequence analysis and classification database, was used to identify the domains of all homologous proteins and compare the similarity between the domains within each compared to the human protein [4]. InterPro recognized both the WD repeat domain and the RING finger domain in the human protein, matching the results found from Pfam. InterPro also recognized both domains in all other homologous proteins, with slight variation on domain position and length that is detailed below.
Domain ClassificationFollowing identification of the WD repeat domain and Zinc RING finger domain within the FANCL protein, the three databases were used together to classify the structural and functional roles of the two domains within the context of FANCL.
Analysis of ResultsThe identification of the WD40 repeat domain and the RING finger domain provide valuable insight into the mechanisms through which FANCL facilitates the monoubiquitination of the ID complex. From the information gathers from the three protein domain analysis databases, the WD40 repeat region is more than likely responsible for the protein-protein interactions of FANCL with the other Fanconi Anemia core complex proteins. On the other hand, the RING finger domain is a well characterized E3 ubiquitin ligase and is directly responsible for the transfer of ubiquitin from Ube2t to FANCD2, the vital signalling mechanism of the Fanconi Anemia pathway. The information gathered here provides a starting point for further research into how mutations affect these two domains in terms of the function of the pathway and the overall variation in phenotype of FANCL-cause Fanconi Anemia.
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References
[1] CHAP Protein Structural Domains: Definition and Prediction Ezkurdia, Iakes Tress, Michael L. John Wiley & Sons, Inc. 9780471140863 http://dx.doi.org/10.1002/0471140864.ps0214s66 10.1002/0471140864.ps0214s66 Current Protocols in Protein Science 2001
[2] The Pfam protein families database: R.D. Finn, A. Bateman, J. Clements, P. Coggill, R.Y. Eberhardt, S.R. Eddy, A. Heger, K. Hetherington, L. Holm, J. Mistry, E.L.L. Sonnhammer, J. Tate, M. Punta
[3] Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
[4] Alex Mitchell et. al (2015). The InterPro protein families database: the classification resource after 15 years. Nucleic Acids Research, Jan 2015; doi: 10.1093/nar/gku1243
[2] The Pfam protein families database: R.D. Finn, A. Bateman, J. Clements, P. Coggill, R.Y. Eberhardt, S.R. Eddy, A. Heger, K. Hetherington, L. Holm, J. Mistry, E.L.L. Sonnhammer, J. Tate, M. Punta
[3] Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
[4] Alex Mitchell et. al (2015). The InterPro protein families database: the classification resource after 15 years. Nucleic Acids Research, Jan 2015; doi: 10.1093/nar/gku1243
Image Resources
Figure 1: FANCL domains from Pfam
Figure 2: FANCL domains from SMART
Figure 3: FANCL domains from InterPro
Figure 4: FANCL crystal structure
Figure 2: FANCL domains from SMART
Figure 3: FANCL domains from InterPro
Figure 4: FANCL crystal structure