DEPDC5

The DEP domain derives its name from the proteins Dishevelled, Egl-10 and Pleckstrin, each of which contain a variant of this domain.[8] It spans 82 residues and is 343 amino acids from the C-terminus. A SWISS-MODEL predicts two beta sheets and three alpha helices contained within the domain.[9]

While its exact function is not known, the DEPDC5 DEP domain has the highest structural similarity to the DEP domain of DVL1 when performing a CBLAST at NCBI.[10] The alignment scores an Evalue of 1.00e-08 and indicates 30% identity between the DEP domains of the two proteins. In DVL1, the DEP domain is involved in localization of the protein to the plasma membrane as part of the Wnt signaling pathway.[11]

The DUF 3608 domain sits 99 amino acids from the N-terminus and itself spans 280 amino acids. PELE predicts at least one beta sheet and two alpha helices within this domain.[12] It also contains 26 highly conserved residues and several post-translation modifications. Both occurrences are addressed later in this article.

Evidence for the function of DUF 3608 has been uncovered in the yeast homolog Iml1p. Imlp1's DUF 3608 is thought to aid in binding to two protein partners, Npr2 and Npr3. Together, these three proteins form the Iml1-Npr2-Npr3 complex and are involved in "non-nitrogen starvation" autophagy regulation. The researchers who uncovered this propose renaming DUF 3608 to RANS (Required for Autophagy induced under Non-nitrogen Starvation conditions).[13]

Based on unanimous consensus by the secondary structure prediction tool PELE, DEPDC5 contains at least ten alpha helices and nine beta sheets. The locations of these secondary structures are illustrated in the image below: red highlights are alpha helices and blue highlights are beta sheets.

Fungi are the most distantly related organisms to contain a protein orthologous to human DEPDC5, including Saccharomyces cerevisiae and Albugo laibachii. In the fungi, the protein name is Iml1p, or vacuolar membrane-associated protein Iml1. Name deviations in other organisms include CG12090 (Drosophila) and AGAP007010 (mosquito).[7] Conservation is high between humans and other vertebrate species, ranging from 74% identity in cichlids to 99% identity in chimpanzees.[14]

The following table summarizes an analysis of 20 proteins orthologous to human DEPDC5.

30 residues have been conserved since animals and fungi diverged, with 26 of these located in the DUF 3608 domain.[16] The following multiple sequence alignment illustrates this conservation of the DUF domain; representatives from invertebrate and fungal clades are aligned to the human DUF 3608 with completely conserved residues colored green.

There are no known human DEPDC5 paralogs,[14] but there are 64 human proteins containing a homologous DEP domain.[17] There are also no identified paralogs for the yeast protein Iml1, the most distantly related ortholog of human DEPDC5.[14]