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Shisa-8 is a protein encoded by theThe Human gene C22orf17 (Chromosome 22, Open Reading Frame 17). The Shisa-8 protein is predicted to interact with alpha-amino-3-hydroxy-5-methyl-4-isooxazole-propionic acid (AMPA) receptors and is predicted to be apart of the complex.[1] AMPA receptors are predicted to have effects on learning, memory, and gating properties in neurons.[2][3]
Aliases
editthe protein Shisa-8 has multiple aliases, including C22orf17, CTA-250D10.17, and Putative Protein Shisa-8.[4]
Gene
editLocus
The genetic location of the C22orf17 gene lies between two genes being MIR33A and TNFRSF13C respectively and is found from 41,909,533 to 41,915,053 spanning 5,532 base pairs. Specifically, C22orf17 is located on the minus (-) strand of Chromosome 22 at cytogenetic band q13.2.[5]
Exons
C22orf17 has a total of 4 exons and 3 introns and spans approximately 5,532 base pairs. all of the introns are gt-ag.[6]
RNA
Expression of the C22orf17 gene was noted in the cerebellum, olfactory bulb, and adrenal gland with little to no expression in other areas of the brain.[7][8] One study showed that EST clones of similar sequences in brain and colon tumors and in lymphoma libraries were discovered, showing an association with cancer.[9]
Protein
editStructure
Shisa-8 is a membrane bound protein enriched with AMPA receptors that has 4 isoforms.[10]It is a class of transporters only found in the membrane currently.[11] The protein is comprised of several regions including a N-terminus cysteine rich region extracellular domain, a transmembrane region, C-terminus region with a proline rich region and a PDZ II domain. This cysteine rich region is highly conserved, showing its importance in interacting with AMPA receptors. The PDZ region also allows this protein to interact with other PDZ containing proteins.[12] It also contains a Wnt and FGF signaling domain critical for brain development or neurotransmitter regulation.[13],[14]
Isoforms
C22orf17 has 4 isoforms being isoform 1,2,3 and X1. Exon 1,2, and 4 are all the same length and location in each isoform, with Exon 3 being different in each one. The longest of these isoforms is isoform 1 producing a protein that is a total of 492 amino acids.[15]
Molecular weight and Amino Acid Length
| Isoform Protein # | Accession # | mRNA length (nt) | Protein Length (aa) | Molecular Weight (kDa) | Variation in Exon 3 (nt) |
|---|---|---|---|---|---|
| 1 | NP_001340367 | 2108 | 492 | 47.5 | 431 |
| 2 | NP_001340368 | 2000 | 456 | 43.9 | 323 |
| 3 | NP_001193949 | 1823 | 397 | 38.6 | 146 |
| X1 | XP_006724319 | 1988 | 452 | 47.3 | No information |
Evolution
editHomology Shisa-8 orthologs were found in vertebrates and even includes cartilaginous fish.[17]. Theories of Shisa-8 origins conclude that it either resulted from a gene duplication from Shisa-9, or was present in the last common ancestor of vertebrates.[18] Of all vertebrates, the most divergent ortholog found was a Petromyzon marinus(Sea Lamprey). Shisa-8 diverged from Petromyzon marinus approximately 462 million years ago [19]
Rate Of Evolution Using Cytochrome C and Fibrinogen Alpha divergence rates, Shisa-8 divergence rates were more similar to Fibrinogen Alpha divergence rates. This seems to indicate that Shisa-8's rate of mutation is similar to that of Fibrinogen Alpha.
References
edit- ^ NCBI:C22orf17 gene. "NCBI". Retrieved 29 September 2024.
- ^ An integrated multi-omics analysis identifies novel regulators of circadian rhythm and sleep disruptions induced by changed photoperiod in Antarctica. "Research Square". Retrieved 29 September 2024.
- ^ Auxiliary subunits of the AMPA receptor: The Shisa family of proteins. "Science Direct". Retrieved 29 September 2024.
- ^ GeneCards:Shisa8 gene. "GeneCards". Retrieved 29 September 2024.
- ^ GeneCards:Shisa8 gene. "GeneCards". Retrieved 29 September 2024.
- ^ NCBI:Shisa8 Page. "NCBI". Retrieved 29 September 2024.
- ^ GeneCards:Shisa8 gene. "GeneCards". Retrieved 29 September 2024.
- ^ Auxiliary subunits of the AMPA receptor: The Shisa family of proteins. "Science Direct". Retrieved 29 September 2024.
- ^ Tnfrsf13c (Baffr) Is Mis-Expressed in Tumors with Murine Leukemia Virus Insertions at Lvis22. "Science Direct". Retrieved 29 September 2024.
- ^ NCBI:Shisa8 Page. "NCBI". Retrieved 29 September 2024.
- ^ Human Protein Atlas:Shisa-8. "Human Protein Atlas". Retrieved 29 September 2024.
- ^ AMPA Receptor Auxiliary Proteins of the CKAMP Family "International Journal of Molecular Sciences". Retrieved 29 September 2024.
- ^ Transcriptional Analysis of Apoptotic Cerebellar Granule Neurons Following Rescue by Gastric Inhibitory Polypeptide. "International Journal of Molecular Sciences". Retrieved 29 September 2024.
- ^ Spontaneous Development of Alzheimer's Disease‐associated Brain Pathology in a Shugoshin‐1 Mouse Cohesinopathy Model "Aging Cell". Retrieved 29 September 2024.
- ^ NCBI:Shisa8 Page. "NCBI". Retrieved 29 September 2024.
- ^ NCBI:Shisa8 Page. "NCBI". Retrieved 29 September 2024.
- ^ GeneCards:Shisa8 gene. "GeneCards". Retrieved 29 September 2024.
- ^ Unexpected Diversity in Shisa-like Proteins Suggests the Importance of Their Roles as Transmembrane Adaptors."ScienceDirect". Retrieved 6 October 2024.
- ^ NCBI Protein Blast."NCBI". Retrieved 6 October 2024.