# RASGEF1C

RASGEF1C (Ras-Guanine Nucleotide Exchange Factor 1C) is a human protein coding gene that encodes the ras-GEF domain containing family member 1C protein. Human RASGEF1C functions in activating GTPase via Guanine Nucleotide Exchange and it has been found to be associated with neurodegenerative disorders.
The human RASGEF1C gene is a 108,417-base-pair long protein-coding gene located on the minus strand at 5q35.3.
The human RASGEF1C gene has 14 exons and transcribes a 2297-nucleotide mRNA transcript.

## Protein

The human RASGEF1C gene encodes only one protein isoform: ras-GEF domain-containing family member 1C protein. This protein is 466 amino acids in length, and it has been predicted to function as a guanine nucleotide exchange factor.
Without undergoing post-translation modifications, the human RASGEF1C protein is 52.9 kdal.

### Secondary Structure

The human RASGEF1C protein consists of 8 beta sheets and 268 alpha helices.

## Expression and regulation

The RASGEF1C gene is ubiquitously expressed across all tissues, with high expression in the brain and salivary glands.
In humans, the abundance of the RASGEF1C protein is 0.011 ppm

### Cellular localization

The human RASGEF1C protein is localized in the cytoplasm.

### Post-translational modifications

The RASGEF1C protein has 11 phosphorylation sites, and one O-glycosylation site.

## Interacting proteins

Human RASGEF1C protein is known to interact with TNK2, a tyrosine kinase non-receptor 2, which functions in inhibiting GTPase

## Evolution

Human RASGEF1C protein paralogs
The Human RASGEF1C protein has two paralogs in humans, RASGEF1A and RASGEF1B.
| Human Protein | Accession Number | Sequence Length (aa) | Identity to Human RASGEF1C Protein (%) | Similarity to Human RASGEF1C Protein (%) |
| RASGEF1C | NP_778232 | 466 | 100 | 100 |
| RASGEF1B | NP_689758 | 473 | 67.7 | 77.6 |
| RASGEF1A | NP_001269791 | 489 | 51.9 | 67.3 |
Human RASGEF1C protein divergence over time
The Human RASGEF1C protein evolved at a slower rate than human fibrinogen alpha, but at a slightly faster rate than cytochrome c over time, having a slow to intermediate rate of evolution over time.
Human RASGEF1C protein orthologs
The Human RASGEF1C protein has orthologs in mammals, marsupials, aves, reptiles, amphibians, fish, insects, and lesser invertebrates. The most distant RASGEF1C ortholog is present in Hood Corals, where divergence of the protein first occurred.
| Genus and Species | Common Name | Date of Divergence (MYA) | Accession Number | Sequence Length (aa) | Identity to Human RASGEF1C Protein | Similarity to Human RASGEF1C Protein |
| Homo sapiens | Humans | 0 | NP_778232 | 466 | 100 | 100 |
| Felis Catus | Domestic Cat | 94 | XP_011279828 | 466 | 96.6 | 98.7 |
| Equus caballus | Horse | 94 | XP_023472779 | 466 | 94 | 92.7 |
| Trichosurus vulpecula | Brushtail Possum | 160 | XP_036608336 | 471 | 84.1 | 89.9 |
| Sarcophilus harrisii | Tasmanian Devil | 160 | XP_031809660 | 501 | 77.9 | 83.3 |
| Ficedula albicollis | Collard Flycatcher | 319 | XP_005053468 | 472 | 82 | 89 |
| Leucopsar rothschildi | Bali Myna | 319 | NXB51188 | 475 | 81.3 | 88.4 |
| Phoenicopterus ruber | Flamingo | 319 | KFQ86429 | 456 | 75.6 | 83.4 |
| Emydura macquarii | Australian Shortneck Turtle | 319 | XP_067422604 | 472 | 81.6 | 88.4 |
| Sphaerodactylus townsendi | Townsend's Least Gecko | 319 | XP_048347148 | 473 | 81.9 | 89.2 |
| Crocodylus porosus | Saltwater Crocodile | 319 | XP_019390718.1 | 516 | 73.5 | 80.5 |
| Microcaecilia unicolor | Cayenne Caecilian | 352 | XP_030067951 | 471 | 77.2 | 85.8 |
| Xenopus laevis | African Clawed Frog | 352 | XP_041435716 | 476 | 66.7 | 77.6 |
| Hippocampus comes | Tigertail Seahorse | 429 | XP_019730368 | 527 | 68.8 | 77.3 |
| Heptranchias perlo | Sharpnose Sevengill Shark | 462 | XP_067851928.1 | 472 | 76.4 | 84.6 |
| Myxine glutinosa | Atlantic Hagfish | 563 | XP_067981376 | 466 | 52.4 | 66.3 |
| Habropoda laboriosa | Southeastern Blueberry Bee | 686 | KOC59508 | 477 | 50.5 | 65.9 |
| Leguminivora glycinivorella | Soybean Pod Borer | 686 | XP_048006501 | 555 | 31.3 | 43.3 |
| Schistocerca piceifrons | Central American Locust | 686 | XP_047109664 | 496 | 49.5 | 64.5 |
| Mizuhopecten yessoensis | Japanese Weathervane Scallop | 686 | XP_021342903 | 497 | 45.4 | 59.6 |
| Stylophora pistillata | Hood Coral | 686 | PFX24589 | 579 | 35.4 | 49.9 |

## Clinical significance

The GCG repeat in the 5'UTR region of the human RASGEF1C gene is known to be naturally selected for during late and on-set neurodegenerative disorders. In addition, the GCG repeat from nucleotide 92 to nucleotide 107 on the 5'UTR is the binding site for the transcription factor Vts1 and the site of a common SNP, resulting in a deletion of the GCG repeat region.