This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Protein domains of COL1A1
PFAM
There were 15 PFAM matches with the FASTA protein sequence. The following is a list of the three domains found:
von Willebrand factor type C domain (VWC)
The VWC domain is found in many plasma membrane proteins and mutations in this domain often lead to human diseases. Proteins with this domain often participate in biological functions, including cell adhesion and signal transduction. [1]
Collagen triple helix repeat (found 12 times)
Collagens are involved in formation of connective tissue in humans and are often extra-cellular in nature. This domain contains 20 repeats of three amino acids: glycine and two others. The other two amino acids are often proline or hydroxyproline but may actually be any amino acid residue. Post-translational modification must take place in order for the hydroxyproline to be present. [6]
Fibrillar collagen C-terminal domain (COLFI)
Collagen proteins contain many globular domains and helical repeats. Globular domains are often involved in binding molecules, however the exact function is unknown for the COLFI domain. One such domain is found at the C-terminus of a fibrillar collagen. [2]
SMART
Three different types of domains were found using SMART analysis:
VWC
Von Willebrand factor type C repeat domains have been found in hundreds of proteins involved in the extracellular matrix of cells. These have been previously shown to bind to TGF-Beta molecules and may be involved in growth factor signaling. There is also additional evidence that this domain may be evolutionarily related to fibronectin type 1 domains based upon both structure and sequence. [4] Mutations found in proteins containing COLFI domains have been associated with several bone and connective tissues disorders [5].
COLFI
Low complexity (LC)
PROSITE
The von Willebrand factor type C repeat domain was found twice within this protein using PROSITE. According to this analysis, this is a domain that is 70 amino acids long with 10 cysteines. This domain is commonly found in other proteins known to form large complexes, further supporting the hypothesis that this domain may be involved in complex formation. [2,3]
Figure 1. Hypothetical layout of domains found in COL1A1. Green domain on the left represents the VWC domain, while the orange domain represents the COLFI domain. The remaining blue oval domains in between represent each collagen triple helix repeat domain.
References
1. Bork P; , FEBS Lett
1992;307:49-54.: The modular architecture of vertebrate collagens. 2. Bork P; , FEBS Lett
1993;327:125-130.: The modular architecture of a new family of growth
regulators related to connective tissue growth factor. 3. Hunt, L., and W. Barker. "Von Willebrand Factor Shares a Distinctive Cysteine-rich Domain with Thrombospondin and Procollagen." Biochemical and Biophysical Research Communications 144.2 (1987): 876-82. 4. O'Leary, J.M. et al. "Solution Structure and Dynamics of a Prototypical Chordin-like Cysteine-rich Repeat (von Willebrand Factor Type C Module) from Collagen IIA." J Bio Chem. Web. 10 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/15466413>. 5. Kuivaniemi H, Tromp G,
Prockop DJ Mutations in fibrillar collagens (types I, II, III, and XI),
fibril-associated collagen (type IX), and network-forming collagen (type X)
cause a spectrum of diseases of bone, cartilage, and blood vessels. Hum Mutat.
1997; 9: 300-15
6. Mayne R, Brewton RG; , Curr Opin Cell Biol 1993;5:883-890.: New members of the collagen superfamily.