Jump to content

Draft:RASGEF1C

From Wikipedia, the free encyclopedia
RASGEF1C
Identifiers
AliasesRASGEF1C, RasGEF domain family member 1C
External IDsMGI: 1921813; HomoloGene: 17918; GeneCards: RASGEF1C; OMA:RASGEF1C - orthologs
Orthologs
SpeciesHumanMouse
Entrez

255426

74563

Ensembl

ENSG00000146090

ENSMUSG00000020374

UniProt

Q8N431

Q9D300

RefSeq (mRNA)

NM_001031799
NM_175062

NM_029004
NM_001347462

RefSeq (protein)

NP_778232

NP_001334391
NP_083280

Location (UCSC)Chr 5: 180.1 – 180.21 MbChr 11: 49.79 – 49.87 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

[edit]

The 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

[edit]
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.[8]

Expression and Regulation

[edit]

The 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

[edit]

The human RASGEF1C protein is localized in the cytoplasm.[11]

Post-Translational Modifications

[edit]
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.[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

[edit]

Human RASGEF1C protein is known to interact with TNK2, a tyrosine kinase non-receptor 2, which functions in inhibiting GTPase[13]

Evolution

[edit]

Human 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
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[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

[edit]

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.[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]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000146090 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020374 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d "RASGEF1C RasGEF domain family member 1C [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-04.
  6. ^ "GeneCards RASGEF1C".
  7. ^ 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)
  8. ^ "I-TASSER results". zhanggroup.org. Retrieved 2024-12-04.
  9. ^ "GDS3113 / 134027". www.ncbi.nlm.nih.gov. Retrieved 2024-12-04.
  10. ^ "PaxDb: Protein Abundance Database". pax-db.org. Retrieved 2024-12-13.
  11. ^ "PSORT II Prediction". psort.hgc.jp. Retrieved 2024-12-04.
  12. ^ "Bioinformatic Tools and Services - DTU Health Tech". services.healthtech.dtu.dk. Retrieved 2024-12-04.
  13. ^ "IntAct Portal". www.ebi.ac.uk. Retrieved 2024-12-04.
  14. ^ 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)
  15. ^ a b c "Home - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-04.
  16. ^ "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2024-12-04.
  17. ^ 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.
  18. ^ "Human hg38 chr5:180,208,992-180,209,711 UCSC Genome Browser v474". genome.ucsc.edu. Retrieved 2024-12-13.
  19. ^ "Variation Viewer". www.ncbi.nlm.nih.gov. Retrieved 2024-12-13.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Draft:RASGEF1C&oldid=1263321373"