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| RASGEF1C | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | RASGEF1C, RasGEF domain family member 1C | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 1921813; HomoloGene: 17918; GeneCards: RASGEF1C; OMA:RASGEF1C - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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.[5]
The human RASGEF1C gene has 14 exons and transcribes a 2297-nucleotide mRNA transcript[5].
Protein
editThe human RASGEF1C gene encodes only one protein isoform: ras-GEF domain-containing family member 1C protein[5]. This protein is 466 amino acids in length, and it has been predicted to function as a guanine nucleotide exchange factor.[6]
Without undergoing post-translation modifications, the human RASGEF1C protein is 52.9 kdal.[7]
Secondary Structure
editThe human RASGEF1C protein consists of 8 beta sheets and 268 alpha helices.[8]
Expression and Regulation
editThe RASGEF1C gene is ubiquitously expressed across all tissues, with high expression in the brain and salivary glands[5].[9]
In humans, the abundance of the RASGEF1C protein is 0.011 ppm[10]
Cellular Localization
editThe human RASGEF1C protein is localized in the cytoplasm.[11]
Post-Translational Modifications
editThe RASGEF1C protein has 11 phosphorylation sites, and one O-glycosylation site.[12] 9 of the phosphorylation sites are at serines and catalyzed by protein kinase C, while the other 2 phosphorylation sites are at lysines and catalyzed by casein kinase II.
Interacting Proteins
editHuman RASGEF1C protein is known to interact with TNK2, a tyrosine kinase non-receptor 2, which functions in inhibiting GTPase[13]
Evolution
editHuman RASGEF1C Protein Paralogs[14][15]
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[14][15]
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[14][15][16]
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 occured.
| 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
editThe 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.[17] 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.[18][19]
References
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000146090 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020374 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d "RASGEF1C RasGEF domain family member 1C [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-04.
- ^ "GeneCards RASGEF1C".
- ^ www.ebi.ac.uk https://www.ebi.ac.uk/jdispatcher/seqstats/saps?species=HUMAN. Retrieved 2024-12-04.
{{cite web}}: Missing or empty|title=(help) - ^ "I-TASSER results". zhanggroup.org. Retrieved 2024-12-04.
- ^ "GDS3113 / 134027". www.ncbi.nlm.nih.gov. Retrieved 2024-12-04.
- ^ "PaxDb: Protein Abundance Database". pax-db.org. Retrieved 2024-12-13.
- ^ "PSORT II Prediction". psort.hgc.jp. Retrieved 2024-12-04.
- ^ "Bioinformatic Tools and Services - DTU Health Tech". services.healthtech.dtu.dk. Retrieved 2024-12-04.
- ^ "IntAct Portal". www.ebi.ac.uk. Retrieved 2024-12-04.
- ^ a b c www.ebi.ac.uk https://www.ebi.ac.uk/jdispatcher/psa/emboss_needle. Retrieved 2024-12-04.
{{cite web}}: Missing or empty|title=(help) - ^ a b c "Home - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-04.
- ^ "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2024-12-04.
- ^ Jafarian, Z.; Khamse, S.; Afshar, H.; Khorshid, H. R. Khorram; Delbari, A.; Ohadi, M. (2021-09-28). "Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder". Scientific Reports. 11 (1): 19235. doi:10.1038/s41598-021-98725-y. ISSN 2045-2322. PMC 8479062. PMID 34584172.
- ^ "Human hg38 chr5:180,208,992-180,209,711 UCSC Genome Browser v474". genome.ucsc.edu. Retrieved 2024-12-13.
- ^ "Variation Viewer". www.ncbi.nlm.nih.gov. Retrieved 2024-12-13.