C1orf186
Chromosome 1 open reading frame 186 is the protein encoding the regulation of hemoglobinization and erythroid cell expansion gene.
Gene
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.Protein
C1orf186 has an estimated molecular weight of 19.4 kDa, and a theoretical pI of 4.76. It is targeted by erythropoietin signaling, which controls erythroid cell expansion and the final stages of erythroblast development.Protein structure
C1orf186 is predicted to have a large alpha helix at the beginning of the translated region, and 4 beta strands towards the end.Regulation
Gene level pegulation
In humans, RHEX is highly expressed in the kidney and lymph tissues with lower, but still significant expression in the pancreas, liver, and lungs. According to Human Protein Atlas, the highest expression is found in the cervix in females and the seminal vesicles in males.Protein level regulation
Human Protein Atlas predicts C1orf186 expression to be localized to the plasma membrane. There are 3 phosphorylation sites found within the translated region of the C1orf186 protein, which are involved in signal transduction pathways.Homology
Orthologs and paralogs
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 | Sequence length | 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
3 phosphorylation sites were experimentally determined, further indicating C1orf186's involvement in differentiation and protein-protein interactions. An N-myristoylation site has also been identified towards the beginning of the protein's translated region.Interacting proteins
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.JP-1: C1orf186 was determined to interact with JP-1 via affinity chromatography from a BioGrid database. JP-1 helps to form junctional membrane complexes.
Clinical significance
Duplications of C1orf186 is associated with slopes of cognitive decline as well as increased cognitive resilience among individuals with Alzheimer's Disease.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.