C1orf186
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C1orf186
[edit]Chromosome 1 open reading frame 186(C1orf186) is the protein encoding the regulation of hemoglobinization and erythroid cell expansion(RHEX) gene.[1]
Gene
[edit]C1orf186 has a cytogenetic location of 1q32.1, contains one transmembrane domain located near the beginning of the translated region, and 7 exons. The gene spans 1205 base pairs.[2]
Protein
[edit]C1orf186 has an estimated molecular weight of 19.4 kDa, and a theoretical pI of 4.76.[3] It is targeted by erythropoietin signaling, which controls erythroid cell expansion and the final stages of erythroblast development.
Protein Structure
[edit]C1orf186 is predicted to have a large alpha helix at the beginning of the translated region, and 4 beta strands towards the end.[4]
Regulation
[edit]Gene Level Regulation
[edit]In humans, RHEX is highly expressed in the kidney and lymph tissues with lower, but still significant expression in the pancreas, liver, and lungs.[5] According to Human Protein Atlas, the highest expression is found in the cervix in females and the seminal vesicles in males.[6]
Protein Level Regulation
[edit]Human Protein Atlas predicts C1orf186 expression to be localized to the plasma membrane.[7] There are 3 phosphorylation sites found within the translated region of the C1orf186 protein, which are involved in signal transduction pathways.[8]
Homology
[edit]Orthologs and Paralogs
[edit]Non-mammalian orthologs have been found in alligators, turtles, and flighted and flightless birds. C1orf186 has mammalian orthologs found most distantly in marsupials. There are no known paralogs of C1orf186 within humans.
| Scientific Name | Common Name | Median Date of Divergence(MYA) | Sequence Length(aa) | Percent Similarity to Human | Percent Identity to Human |
|---|---|---|---|---|---|
| Homo sapiens | Humans | 0 | 172 | 100 | 100 |
| Carlito syrichta | Philippine Tarsier | 69 | 172 | 77.9 | 68.6 |
| Delphinapterus leucas | Beluga Whale | 94 | 172 | 76.7 | 66.9 |
| Rhinolophus sinicus | Chinese Rufous Horseshoe Bat | 94 | 175 | 77.1 | 65.1 |
| Monodelphis domestica | Grey Short-Tailed Opposum | 160 | 202 | 45.7 | 31.9 |
| Gallus gallus | Red Junglefowl | 319 | 159 | 36.5 | 25.4 |
| Apteryx rowi | Okarito Kiwi | 319 | 148 | 39.6 | 27.1 |
| Dermochelys coriacea | Leatherback Sea Turtle | 319 | 65 | 23.3 | 16.3 |
| Alligator mississippiensis | American Alligator | 319 | 62 | 23.3 | 16.3 |
Post-Translational Modifications
[edit]3 phosphorylation sites were experimentally determined, further indicating C1orf186's involvement in differentiation and protein-protein interactions.[9] An N-myristoylation site has also been identified towards the beginning of the protein's translated region.
Interacting Proteins
[edit]SH3GL1: C1orf186 was found to interact with SH3GL1, and as SH3GL1 is implicated in endocytosis helps to point towards a subcellular localization of the plasma membrane for C1orf186. This interaction was determined via two-hybrid assay from an IMEx database.[10]
JP-1: C1orf186 was determined to interact with JP-1 via affinity chromatography from a BioGrid database.[11] JP-1 helps to form junctional membrane complexes.
Clinical Significance
[edit]Duplications of C1orf186 is associated with slopes of cognitive decline as well as increased cognitive resilience among individuals with Alzheimer's Disease.[12]
The most variant of the RHEX gene includes an insertion and deletion mutation identified by NCBI as variant rs555500075, and occurs within 43.8% of the sampled genes containing this variation.[13]
References
[edit]- ^ "Entry - *616088 - REGULATOR OF HEMOGLOBINIZATION AND ERYTHROID CELL EXPANSION; RHEX - OMIM". www.omim.org. Retrieved 2024-09-30.
- ^ "Homo sapiens regulator of hemoglobinization and erythroid cell expansion (RHEX), transcript variant 1, mRNA". Cells. 12 (9). 2024-08-01.
- ^ "SAPS Tool- EMBL-EBI". www.ebi.ac.uk. Retrieved 2024-12-04.
- ^ "PredictProtein - Protein Sequence Analysis, Prediction of Structural and Functional Features". predictprotein.org. Retrieved 2024-12-13.
- ^ "AceView: Gene:C1orf186, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2024-09-30.
- ^ "Tissue expression of RHEX - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2024-12-04.
- ^ "Subcellular - RHEX - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2024-12-13.
- ^ Cohen, P (2000-12-01). "The regulation of protein function by multisite phosphorylation – a 25 year update". Trends in Biochemical Sciences. 25 (12): 596–601. doi:10.1016/s0968-0004(00)01712-6. ISSN 0968-0004. PMID 11116185.
- ^ Nishi, Hafumi; Hashimoto, Kosuke; Panchenko, Anna R (2011-12-07). "Phosphorylation in protein-protein binding: effect on stability and function". Structure. 19 (12): 1807–1815. doi:10.1016/j.str.2011.09.021. PMC 3240861. PMID 22153503.
- ^ Porras, Pablo; Barrera, Elisabet; Bridge, Alan; del-Toro, Noemi; Cesareni, Gianni; Duesbury, Margaret; Hermjakob, Henning; Iannuccelli, Marta; Jurisica, Igor; Kotlyar, Max; Licata, Luana; Lovering, Ruth C.; Lynn, David J.; Meldal, Birgit; Nanduri, Bindu (2020-12-01). "Towards a unified open access dataset of molecular interactions". Nature Communications. 11 (1): 6144. Bibcode:2020NatCo..11.6144P. doi:10.1038/s41467-020-19942-z. ISSN 2041-1723. PMC 7708836. PMID 33262342.
- ^ "C1orf186 Result Summary | BioGRID". thebiogrid.org. Retrieved 2024-12-13.
- ^ Vialle, Ricardo A.; De Paiva Lopes, Katia; Li, Yan; Ng, Bernard; Schneider, Julie A.; Buchman, Aron S.; Wang, Yanling; Farfel, Jose M.; Barnes, Lisa L.; Wingo, Aliza P.; Wingo, Thomas S.; Seyfried, Nicholas T.; De Jager, Philip L.; Gaiteri, Chris; Tasaki, Shinya; Bennett, David A. (2024). "Structural variants linked to Alzheimer's Disease and other common age-related clinical and neuropathologic traits". MedRxiv: The Preprint Server for Health Sciences. doi:10.1101/2024.08.12.24311887. PMC 11343262. PMID 39185527.
- ^ "rs555500075 RefSNP Report - dbSNP - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-13.