Representative proteins

It is currently known that cell division control protein 42 (cdc42) has two isoforms in humans and many other homologues in a diverse array of species. Homologues are proteins that have very similar primary, secondary and tertiary structures.

The closer their homology the more likely they are to have common ancestry. A protein isoform on the other hand is a different form of the same protein. These can be the result of very closely related gene duplicates or the same gene alternatively splicing. We have chosen a select few of these homologues to demonstrate this diversity.

Furthermore, this has allowed us to compare their sequences and displayed a broad view of evolutionary conservation (As can be seen from the multiple sequence alignments (MSA)). Some homologues of different isoforms also exist in these selected species.

For these cases when choosing the protein from the NCBI database, Isoform 1 was always chosen. As the discovery of cdc42 is rather recent, some of the selected homologues have not had a full NCBI curation system review. These are labelled ‘PREDICTED’. The sequence of these proteins may therefore not be as accurate as those that have been fully reviewed and have the potential to be slightly different after review.

The exact functions of most of these homologues have not yet been determined. The small GTPase controls several signalling pathways including endocytosis, cell morphology, migration and the progression of the cell cycle. Thus its control covers a wide set of functions. Moreover, there is a high degree of conservation between the homologues, which can be seen from the MSA tab. This conservation suggests that the function of the cdc42 protein is significant and fundamental to cellular mechanisms across species.

Thus, it can be hypothesised that the function of these homologues is very similar to those demonstrated by the human isoforms. Cdc42 Isoform 1 precursor (Homo sapiens) is extremely similar to the Saccharomyces cerevisiae cdc42. It is therefore able to complement the yeast cdc42-1 mutant. Pseudogenes of the gene encoding this protein also exist, and have been located on chromosomes 3, 4, 5, 7, 8 and 20. Cdc42 Isoform 2 precursor (Homo sapiens) has the same amino acid length however differs at the C-terminus from Cdc42 Isoform 1 precursor (Homo sapiens).

1. cell division control protein 42 homolog isoform 1 precursor [Homo sapiens] - Human (191aa)

Flat file: http://www.ncbi.nlm.nih.gov/protein/NP_001782.1

2. cell division control protein 42 homolog isoform 2 [Homo sapiens] - Human (191aa)

Flat file: http://www.ncbi.nlm.nih.gov/protein/NP_426359.1

These two human isoforms are known to play a primary role in this vasculogenesis process, however very little is known about how extracellular matrix (ECM) rigidity affects cdc42 activity during the process. Research carried out investigating this has generated results that suggest matrix rigidity is a resilient regulator of Cdc42 activity and vacuole formation kinetics. Moreover the enhanced activity of Cdc42 is an important step in early vacuole formation in ECFCs. Furthermore, Cdc42 and its effector complex Par6-atypical protein kinase c (aPKC) regulate numerous steps during epithelial differentiation.

3. Rho family GTPase CDC42 [Saccharomyces cerevisiae S288c] - Yeast (191aa) The yeast Saccharomyces cerevisiae is the distinguished organism commonly used to study rudimentary functions of eukaryotic cells. All of this simple eukaryotic cell’s genes have recently been revealed by an international collaborative effort to determine the complete DNA sequence of its nuclear genome. Cdc42 has been described to have features of chromosome XII.

Flat file: http://www.ncbi.nlm.nih.gov/protein/NP_013330.1

4. cell division control protein 42 homolog [Mus musculus] - Mouse (191aa)

Flat file: http://www.ncbi.nlm.nih.gov/protein/AAH64792.1

5. PREDICTED: cell division control protein 42 homolog isoform X2 [Macaca fascicularis] - Monkey (191aa)

Flat file: http://www.ncbi.nlm.nih.gov/protein/XP_005544568.1