Protein Domains
This page was produced as an assignment for Genetics 564 an undergraduate capstone course at UW-Madison.
What are they?
Protein domains are conserved, distinct sequences of amino acids that represent functional units of a mature protein [1]. Domains give proteins a functional role, and often help proteins have specific interactions. Protein domains are considered evolutionary units, and domains are classified into superfamilies based on their amino acid sequences, structure, and function [2]. Protein domain relationships follow a similar pattern to species phylogenetic relationships in the sense that domain relationships are inferred through similarity and are often displayed in trees, as demonstrated by the TRP ion channel tree shown in Figure 1.
What domains are found in ERCC6?
Protein domain analysis was done using SMART, Pfam, InterPro, and PROSITE. Two major protein domains were identified in the human ERCC6 gene: SNF2_N and HELICc. PROSITE, Pfam, and InterPro all produced the same results. SMART called the SNF2_N region a DEXDc region.
Using the information from the four analysis algorithms, Figure 2 was constructed. I chose to continue forward using the SNF2_N domain instead of the DEXDc domain, because three of the four programs used identified SNF2_N, while only SMART identified DEXDc. In order to gain any information from this analysis, it is important to explore the functions of the two identified domains.
SNF2_N is a member of the SNF2 protein family. Proteins in this family represent a variety of cellular processes, such as transcriptional regulation, chromosome stability, and DNA damage processing, including nucleotide excision repair, which is the process that ERCC6 is critically involved in [3]. In addition, the SNF2_N domain contains protein motifs similar to those found in many DNA and RNA helicases.
HELICc, is the c-terminal domain found in proteins belonging to the helicase superfamilies 1 and 2 [4]. It has helicase activity and functions in ATP binding.
SNF2_N is a member of the SNF2 protein family. Proteins in this family represent a variety of cellular processes, such as transcriptional regulation, chromosome stability, and DNA damage processing, including nucleotide excision repair, which is the process that ERCC6 is critically involved in [3]. In addition, the SNF2_N domain contains protein motifs similar to those found in many DNA and RNA helicases.
HELICc, is the c-terminal domain found in proteins belonging to the helicase superfamilies 1 and 2 [4]. It has helicase activity and functions in ATP binding.
Are the domains present in other organisms?
ERCC6 is a conserved gene, and as a result, it has relatively conserved protein domains. Using both SMART and Pfam, four other species identified by homology were analyzed. These four species all contained the two domains and some of the low complexity regions found in the human gene. In general, species were different in the start and end points of their two conserved domains. Additionally, each species had slight differences in the number and start and end points of their low complexity regions.
Accession numbers used: Human (Q03468), Chimpanzee (H2Q1W1), Mouse (F8VPZ5), Cow (E1BFL2), Zebrafish (F1RDN1)
Accession numbers used: Human (Q03468), Chimpanzee (H2Q1W1), Mouse (F8VPZ5), Cow (E1BFL2), Zebrafish (F1RDN1)
Conclusions
The presence of the SNF2_N and HELICc protein domains make sense, given ERCC6's established role in the nucleotide excision repair pathway and the fact that it is an ATP-dependent helicase protein [5]. The two protein domains suggest that ERCC6 is activated by ATP and works to remodel strands of nucleotides. In transcription, it locally modifies DNA conformation when bound by wrapping the DNA around itself, which modifies RNA polymerase II and DNA interactions. It then relies on other complexes and proteins, some of which it recruits, to ultimately remove DNA lesions that it has identified. The DNA binding that ERCC6 is involved in is reflected by the two major protein domains that I identified.
References
[1] EMBL-EBI protein domain page: https://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[2] Vogel, C., Bashton, M., Kerrison, N. D., Chothia, C., & Teichmann, S. A. (2004). Structure, function and evolution of multidomain proteins. Current opinion in structural biology, 14(2), 208-216. http://people.unica.it/elisabettasoro/files/2012/04/Struttura_proteine.pdf
[3] Eisen, J. A., Sweder, K. S., & Hanawalt, P. C. (1995). Evolution of the SNF2 family of proteins: subfamilies with distinct sequences and functions. Nucleic acids research, 23(14), 2715-2723. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC307096/pdf/nar00014-0153.pdf
[4] Smart domain description: http://smart.embl.de/smart/do_annotation.pl?DOMAIN=SM00490
[5] ERCC6 UniProt sheet. http://www.uniprot.org/uniprot/Q03468
Images and Videos
Header picture: http://beautifulproteins.blogspot.com/
TRP protein picture: Clapham, D. E., Runnels, L. W., & Strubing, C. (2001). The trp ion channel family. Nature Reviews Neuroscience, 2, 387-396. doi:10.1038/35077544
Human silhouette: http://www.freevectors.net/human+silhouette
Chimpanzee silhouette: http://www.vinylsilhouettes.com/chimpanzee-silhouette-wall-decal
Mouse silhouette: http://www.stickthisgraphics.com/Mouse-Silhouette-2-Decal-Sticker-WILD175.htm
Cow silhouette: http://www.publicdomainpictures.net/view-image.php?image=118794&picture=cow-silhouette
Zebrafish silhouette: https://www.colourbox.com/vector/vector-silhouette-of-fish-on-white-background-vector-1651696
This website was created for Genetics 564 by Zachary Beethem, an undergraduate genetics major at UW-Madison.
He can be reached via email: [email protected]
Date of last website update: April 2017
[1] EMBL-EBI protein domain page: https://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[2] Vogel, C., Bashton, M., Kerrison, N. D., Chothia, C., & Teichmann, S. A. (2004). Structure, function and evolution of multidomain proteins. Current opinion in structural biology, 14(2), 208-216. http://people.unica.it/elisabettasoro/files/2012/04/Struttura_proteine.pdf
[3] Eisen, J. A., Sweder, K. S., & Hanawalt, P. C. (1995). Evolution of the SNF2 family of proteins: subfamilies with distinct sequences and functions. Nucleic acids research, 23(14), 2715-2723. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC307096/pdf/nar00014-0153.pdf
[4] Smart domain description: http://smart.embl.de/smart/do_annotation.pl?DOMAIN=SM00490
[5] ERCC6 UniProt sheet. http://www.uniprot.org/uniprot/Q03468
Images and Videos
Header picture: http://beautifulproteins.blogspot.com/
TRP protein picture: Clapham, D. E., Runnels, L. W., & Strubing, C. (2001). The trp ion channel family. Nature Reviews Neuroscience, 2, 387-396. doi:10.1038/35077544
Human silhouette: http://www.freevectors.net/human+silhouette
Chimpanzee silhouette: http://www.vinylsilhouettes.com/chimpanzee-silhouette-wall-decal
Mouse silhouette: http://www.stickthisgraphics.com/Mouse-Silhouette-2-Decal-Sticker-WILD175.htm
Cow silhouette: http://www.publicdomainpictures.net/view-image.php?image=118794&picture=cow-silhouette
Zebrafish silhouette: https://www.colourbox.com/vector/vector-silhouette-of-fish-on-white-background-vector-1651696
This website was created for Genetics 564 by Zachary Beethem, an undergraduate genetics major at UW-Madison.
He can be reached via email: [email protected]
Date of last website update: April 2017