{{Short description|Human Gene}}
{{#invoke:Infobox gene|getTemplateData|QID=Q18053802}}
'''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.<ref name=":0">{{Cite web |title=RASGEF1C RasGEF domain family member 1C [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/?term=AF449764 |access-date=2024-12-04 |website=www.ncbi.nlm.nih.gov}}</ref>
The human RASGEF1C gene has 14 exons and transcribes a 2297-nucleotide mRNA transcript.<ref name=":0" />
== Protein == The human RASGEF1C gene encodes only one protein isoform: ras-GEF domain-containing family member 1C protein.<ref name=":0" /> This protein is 466 amino acids in length, and it has been predicted to function as a guanine nucleotide exchange factor.<ref>{{Cite web |title=RASGEF1C Gene - GeneCards | RGF1C Protein | RGF1C Antibody |url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=RASGEF1C}}</ref>
Without undergoing post-translation modifications, the human RASGEF1C protein is 52.9 kdal.<ref>{{Cite web |title=SAPS |url=https://www.ebi.ac.uk/jdispatcher/seqstats/saps?species=HUMAN |access-date=2024-12-04 |website=www.ebi.ac.uk}}</ref>
=== Secondary Structure === thumb|The Human RASGEF1C Protein Tertiary Structure with Secondary Structure and Phosphorylation Sites Highlighted. (Green is Beta Sheets, Red is Alpha Helices, and Spheres Represent Phosphorylation Sites). The human RASGEF1C protein consists of 8 beta sheets and 268 alpha helices.<ref>{{Cite web |title=SAPS |url=https://www.ebi.ac.uk/jdispatcher/seqstats/saps?species=HUMAN |access-date=11 January 2025 |website=www.ebi.ac.uk}}</ref>
== Expression and regulation == The RASGEF1C gene is ubiquitously expressed across all tissues, with high expression in the brain and salivary glands.<ref name=":0" /><ref>{{Cite web |title=GDS3113 / 134027 |url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3113:134027 |access-date=2024-12-04 |website=www.ncbi.nlm.nih.gov}}</ref>
In humans, the abundance of the RASGEF1C protein is 0.011 ppm<ref>{{Cite web |title=PaxDb: Protein Abundance Database |url=https://pax-db.org/protein/9606/ENSP00000377037 |access-date=2024-12-13 |website=pax-db.org}}</ref>
=== Cellular localization === The human RASGEF1C protein is localized in the cytoplasm.<ref>{{Cite web |title=PSORT II Prediction |url=https://psort.hgc.jp/form2.html |access-date=2024-12-04 |website=psort.hgc.jp}}</ref>
=== Post-translational modifications === [[File:HumanRASGEF1C Conceptual Translation exc3UTR.png|thumb|Conceptual Translation of Human RASGEF1C mRNA transcript and protein, highlighting important domains and sites (post-translational modifications, protein binding sites, and SNPs).]] The RASGEF1C protein has 11 phosphorylation sites, and one O-glycosylation site.<ref>{{Cite web |title=Bioinformatic Tools and Services - DTU Health Tech |url=https://services.healthtech.dtu.dk/ |access-date=2024-12-04 |website=services.healthtech.dtu.dk}}</ref>
== Interacting proteins == Human RASGEF1C protein is known to interact with TNK2, a tyrosine kinase non-receptor 2, which functions in inhibiting GTPase<ref>{{Cite web |title=IntAct Portal |url=https://www.ebi.ac.uk/intact/search?query=rasgef1c |access-date=2024-12-04 |website=www.ebi.ac.uk}}</ref>
== Evolution == '''Human RASGEF1C protein paralogs'''
The Human RASGEF1C protein has two paralogs in humans, RASGEF1A and RASGEF1B.<ref name=":1" /><ref name=":2" /> {| class="wikitable" |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 |} thumb|Divergence of RASGEF1C Orthologs, Cytochrome c, and Fibrinogen Alpha from Respective Human Proteins over time in million years ago (MYA).
'''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.<ref name=":1" /><ref name=":2" />
'''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.<ref name=":1">{{Cite web |title=ebi |url=https://www.ebi.ac.uk/jdispatcher/psa/emboss_needle |access-date=2024-12-04 |website=www.ebi.ac.uk}}</ref><ref name=":2">{{Cite web |title=Home - Protein - NCBI |url=https://www.ncbi.nlm.nih.gov/protein |access-date=2024-12-04 |website=www.ncbi.nlm.nih.gov}}</ref><ref>{{Cite web |title=TimeTree :: The Timescale of Life |url=https://timetree.org/ |access-date=2024-12-04 |website=timetree.org |language=en}}</ref> {| class="wikitable" |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.<ref>{{Cite journal |last1=Jafarian |first1=Z. |last2=Khamse |first2=S. |last3=Afshar |first3=H. |last4=Khorshid |first4=H. R. Khorram |last5=Delbari |first5=A. |last6=Ohadi |first6=M. |date=2021-09-28 |title=Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder |journal=Scientific Reports |volume=11 |issue=1 |pages=19235 |doi=10.1038/s41598-021-98725-y |issn=2045-2322 |pmc=8479062 |pmid=34584172|bibcode=2021NatSR..1119235J }}</ref> 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.<ref>{{Cite web |title=Human hg38 chr5:180,208,992-180,209,711 UCSC Genome Browser v474 |url=https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr5:180208992-180209711&hgsid=2372272905_Ju94Y90QiNoEYyyqEAbhYZWOnPOg |access-date=2024-12-13 |website=genome.ucsc.edu}}</ref><ref>{{Cite web |title=Variation Viewer |url=https://www.ncbi.nlm.nih.gov/variation/view |access-date=2024-12-13 |website=www.ncbi.nlm.nih.gov}}</ref>
== References == {{Reflist}}