This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Protein Domains and Motifs
One of the most common misconceptions about the words "domain" and "motif" is that they are interchangeable. For proteins, the word domain refers to a piece of the overall protein that is capable of functioning on it's own without the entire structure. A protein motif is the actual amino acid sequence of the polypeptide chain. This is also referred to as the primary structure of the protein. When several parts of the primary structure pack together to form a functional unit, this becomes a protein domain [1]. These domains are often similar or conserved across many different taxa.
The majority of proteins are are multidomain proteins meaning they have more than one functional domain present in their structure [2]. These multiple domains probably existed independently at some point during the evolutionary timeline. Multidomain proteins arise from transposition of mobile genetic elements, large scale gene mutations - deletions, duplication, translocations etc. - homologous recombination and DNA polymerase replication errors [3].
For this analysis of FRMD7 protein domains, Pfam and SMART were used to analyze the protein sequence of FRMD7 to find regions known to be a part of specific protein domain family. Figure 1 below is the result obtained from Pfam, and Figure 2 is the result from SMART.
The majority of proteins are are multidomain proteins meaning they have more than one functional domain present in their structure [2]. These multiple domains probably existed independently at some point during the evolutionary timeline. Multidomain proteins arise from transposition of mobile genetic elements, large scale gene mutations - deletions, duplication, translocations etc. - homologous recombination and DNA polymerase replication errors [3].
For this analysis of FRMD7 protein domains, Pfam and SMART were used to analyze the protein sequence of FRMD7 to find regions known to be a part of specific protein domain family. Figure 1 below is the result obtained from Pfam, and Figure 2 is the result from SMART.
The Pfam figure above, broke FRMD7 four main domains, FERM N, FERM M, FERM C and FERM adjacent. The first three domains can be grouped together to form the FERM domain, which gives FRMD7 the first part of it's name. The FERM domain is very well conserved across taxa, and is involved with localizing proteins to the cytoskeleton [4]. Specifically, the FERM domain is involved directly with the interface between the cytoskeleton and the plasma membrane. Also, the FERM domain is usually located near the N-terminus of the protein, and is the most common site of mutations associated with nystagmus [5][6].
The other region, FERM adjacent is not well categorized. It is not always present in FERM domain containing proteins, and is thought to play a role in regulatory adaptation of the protein [7].
The other region, FERM adjacent is not well categorized. It is not always present in FERM domain containing proteins, and is thought to play a role in regulatory adaptation of the protein [7].
Figure 2, obtained from SMART, shows FRMD7 broken into four parts, like figure 1, except the divisions are slightly different. SMART broke FRMD7 into the blue B41 domain, FERM C domain, FERM adjacent, and a low complexity region. The B41 region is simply the FERM N and FERM M domains grouped together due to the similarity of their structure and function. Along with FERM C, these two regions make up the FERM domain as a whole.
The main difference between this figure and the Pfam analysis is the presence of the pink low complexity region. This region is a 21 residue long amino acid sequence that has been found to have some similarity with other proteins, but has yet to be fully studied or categorized.
The main difference between this figure and the Pfam analysis is the presence of the pink low complexity region. This region is a 21 residue long amino acid sequence that has been found to have some similarity with other proteins, but has yet to be fully studied or categorized.
Analysis and Discussion
Both Pfam and SMART yielded similar domains for FRMD7. The FERM domain is well understood and associated with proteins that localize with with elements of the cytoskeleton. FRMD7 is hypothesized to co-localize with actin in neuron cells to aid in the outgrowth of the axonal growth cone to allow neurons to communicate with other cells.
References
[1] Richardson J. S. (1981).
The anatomy and taxonomy of protein structure. Advances in Protein Chemistry. (34)167. doi: 10.1016/S0065-3233(08)60520-3.
[2] Apic, G., Gough, J., and Teichmann, S. A. (2001). Domain combinations in archaeal, eubacterial and eukaryotic proteomes. Journal of Molecular Biology, 310(2), 311. doi: 10.1006/jmbi.2001.4776
[3] Bork, P. and Doolittle, R. F (1992).
Proposed aquisition of animal protein domain by bacteria. Proceeding of the National Adademy of Science. 89(19), 8990. doi: 10.1073/pnas.8919.8990
[4] Chishti A. H., Kim A. C., Marfatia S. M., Lutchman M., Hanspal M., Jindal H., Liu S. C., Low P. S., Rouleau G. A., Mohandas N., Chasis J. A., Conboy J. G., Gascard P., Takakuwa Y., Huang S. C., Benz E. J., Bretscher A., Fehon R. G., Gusella J. F., Ramesh V., Solomon F., Marchesi V. T., Tsukita S., Tsukita S., Hoover K.B. (1998).
The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends in Biochemical Science. 23 (8): 281–2. doi: 10.1016/S0968-0004(98)01237
[5] Pearson M. A., Reczek D., Bretscher A., Karplus P. A. (2000). Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell 101(3), 259–70. doi: 10.1016/S0092-8674(00)80836-3
[6] Thomas, M. G., Crosier, M., Lindsay, S., Kumar, A., Thomas, S., Araki, M., Talbot, C., McLean, R. J., Surendran, M., Taylor, K., Leroy, B. P., Moore, A. T., Hunter, D. G., Hertle, R. W., Tarpey, P., Langmann, A., Lindner, S., Brandner, M., Gottlob., I. (2011)
The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain, a Journal of Neurology, 2011(134), 892, doi: 10.1093/brain/awq373
[7] Baines A. J. (2006)A FERM-adjacent (FA) region defines a subset of the 4.1 superfamily and is a potential regulator of FERM domain function. Biomedical Central Genomics. 7(85). doi: 10.1186/1471-2164-7-85
The anatomy and taxonomy of protein structure. Advances in Protein Chemistry. (34)167. doi: 10.1016/S0065-3233(08)60520-3.
[2] Apic, G., Gough, J., and Teichmann, S. A. (2001). Domain combinations in archaeal, eubacterial and eukaryotic proteomes. Journal of Molecular Biology, 310(2), 311. doi: 10.1006/jmbi.2001.4776
[3] Bork, P. and Doolittle, R. F (1992).
Proposed aquisition of animal protein domain by bacteria. Proceeding of the National Adademy of Science. 89(19), 8990. doi: 10.1073/pnas.8919.8990
[4] Chishti A. H., Kim A. C., Marfatia S. M., Lutchman M., Hanspal M., Jindal H., Liu S. C., Low P. S., Rouleau G. A., Mohandas N., Chasis J. A., Conboy J. G., Gascard P., Takakuwa Y., Huang S. C., Benz E. J., Bretscher A., Fehon R. G., Gusella J. F., Ramesh V., Solomon F., Marchesi V. T., Tsukita S., Tsukita S., Hoover K.B. (1998).
The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends in Biochemical Science. 23 (8): 281–2. doi: 10.1016/S0968-0004(98)01237
[5] Pearson M. A., Reczek D., Bretscher A., Karplus P. A. (2000). Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell 101(3), 259–70. doi: 10.1016/S0092-8674(00)80836-3
[6] Thomas, M. G., Crosier, M., Lindsay, S., Kumar, A., Thomas, S., Araki, M., Talbot, C., McLean, R. J., Surendran, M., Taylor, K., Leroy, B. P., Moore, A. T., Hunter, D. G., Hertle, R. W., Tarpey, P., Langmann, A., Lindner, S., Brandner, M., Gottlob., I. (2011)
The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain, a Journal of Neurology, 2011(134), 892, doi: 10.1093/brain/awq373
[7] Baines A. J. (2006)A FERM-adjacent (FA) region defines a subset of the 4.1 superfamily and is a potential regulator of FERM domain function. Biomedical Central Genomics. 7(85). doi: 10.1186/1471-2164-7-85
Site created by: Kristen Klimo
Last updated: 5/11/2012
University of Wisconsin-Madison
Last updated: 5/11/2012
University of Wisconsin-Madison