EVI5L
EVI5L is a protein that in humans is encoded by the EVI5L gene. EVI5L is a member of the Ras superfamily of monomeric guanine nucleotide-binding proteins, and functions as a GTPase-activating protein with a broad specificity. Measurement of in vitro Rab-GAP activity has shown that EVI5L has significant Rab2A- and Rab10-GAP activity.
Gene
The EVI5L gene is 34,701 base pairs long and has an unprocessed mRNA that is 3,756 nucleotides in length. It consists of 19 exons that encode for an 805 amino acid protein.Locus
EVI5L is located on the short arm of chromosome 19 in region 1, band 3, and sub-band 2 starting at 7,830,275 base pairs and ending at 7,864,976 base pairs. It is encoded for on the plus strand. It is located near the CLEC4M gene, which is involved in peptide antigen transport.Homology and Evolution
Homologous domains
EVI5L contains a RAB-GAP TBC domain, which is involved with regulating membrane trafficking by cycling between inactive and active conformations. It also has the apolipophorin-III and tetratricopeptide repeat domains. Apolipophorin-III play vital roles in the transport of lipids and lipoprotein metabolism, while TPR mediates protein-protein interactions and the assembly of multi protein complexes. These three domains are highly conserved in EVI5L orthologs.Paralogs
There are 7 moderately related proteins in humans that are paralogous to the RAB-GAP TBC domain of EVI5L. All of these proteins are in the guanosine nucleotide-binding protein family| Paralogous Protein | Protein Name | Sequence length | Amino Acid Identity |
| EVI5 | Ecotropic viral integration site 5 | 810 aa | 51% |
| TBC1D14 | TBC1 domain family, member 14 | 693 aa | 19% |
| RABGAP1 | RAB GTPase activating protein 1 | 1069 aa | 18% |
| RABGAP1L | RAB GTPase activating protein 1-like | 815 aa | 18% |
| TBC1D12 | TBC1 Domain Family Member 12 | 775 aa | 17% |
| TBC1 | Domain Family, Member 1 | 1168 aa | 15% |
| TBC1D4 | TBC1 domain family, member 4 | 1298 aa | 13% |
Orthologs
There are 63 orthologs of EVI5L that have been identified including mammals, birds, reptiles, and fish. EVI5L is highly conserved among its orthologs but is not present in insects, plants, bacteria, archea or protists.Homologs
The following table lists the homologs of EVI5L:| Genus and Species | Common name | Accession number | Seq. Length | Seq. Identity | Seq. Similarity | Time of Divergence |
| Homo sapiens | Humans | 3756 bp | - | - | - | |
| Pan troglodytes | Common Chimpanzee | 3874 bp | 99% | 99% | 6.3 mya | |
| Canis familiaris | Dog | 2430 bp | 98% | 99% | 94.2 mya | |
| Sus scrofa | Wild Boar | 3673 bp | 95% | 99% | 94.2 mya | |
| Chelonia mydas | Sea Turtle | 3436 bp | 94% | 99% | 294.5 mya | |
| Alligator sinensis | Chinese Alligator | 6780 bp | 82% | 91% | 296.4 mya | |
| Ficedula albicollis | Collared Flycatcher | 2090 bp | 79% | 88% | 324.2 mya | |
| Haplochromis burtoni | Cichlid | 6638 bp | 70% | 84% | 400.1 mya | |
| Danio rerio | Zebrafish | 2856 bp | 69% | 82% | 400.1 mya | |
| Oreochromis niloticus | Nile Tilapia | 6757 bp | 68% | 84% | 400.1 mya |
Protein
The protein of EVI5L consists of 805 amino acid residues. The molecular weight of the mature protein is 92.5 kdal with an isoelectric point of 5.05. EVI5L has an unusually large amount of glutamic acid residues, compared to similar proteins. Most of the protein is neutral, with no positive charge, negative charge, or mixed charge clusters. It has a very small negative hydrophobicity. EVI5L is a soluble protein that localizes in the nucleus. It contains no signal peptide, no mitochondrial targeting motifs and no peroxisomal targeting signal in the C-terminus. There is no transmembrane domain in EVI5L.Isoforms
EVI5L has two isoforms produced by alternative splicing. Isoform 2 is missing in-frame exon 11, making it shorter.Post-Translational Modifications
Post translational modifications of EVI5L that are evolutionarily conserved in majority of the orthologs include glycosylation, glycation, phosphorylation, and sumoylation. There is also one leucine-rich nuclear export signal.Secondary Structure
The entire secondary structure of EVI5L is made up of alpha helices, with no beta sheets present. This is also true for EVI5Ls closest structural paralog, RABGAP1L.Expression
Promoter
The predicted promoter for the EVI5L gene spans 664 base pairs from 7,910,867 to 7,911,530 with a predicted transcriptional start site that is 114 base pairs and spans from 7,911,346 to 7,911,460. The promoter region and beginning of the EVI5L gene is not conserved past primates. This region was used to determine transcription factor interactions.Some of the main transcription factors predicted to bind to the promoter includes: activator-, mediator- and TBP-dependent core promoter element for RNA polymerase II transcription from TATA-less promoters, p53 tumor suppressor, brachyury gene, mesoderm developmental factor, EGR/nerve growth factor induced protein C & related factors, and GLI zinc finger family.