Biology:Atrophin 1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Atrophin-1 is a protein that in humans is encoded by the ATN1 gene.[1] The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat.[2] The function of Atrophin-1 has not yet been determined.[3] There is evidence provided by studies of Atrophin-1 in animals to suggest it acts as a transcriptional co-repressor.[3] Atrophin-1 can be found in the nuclear and cytoplasmic compartments of neurons.[3] It is expressed in nervous tissue.[4]

Function

The function of Atrophin-1 has not been defined yet. It is widely hypothesized that Atrophin-1 functions as a transcriptional co-repressor.[5] A transcriptional co-repressor is a protein that indirectly suppresses the activity of specific genes by interacting with DNA-binding proteins.[5]

Clinical significance

The ATN1 gene has a segment of DNA called the CAG trinucleotide repeat.[5] It is made up of cytosine, adenine, and guanine.[5] The number of CAG repeats in the ATN1 gene in a healthy person will range from six to thirty-five repeats.[5] CAG repeats that exceed thirty-five can cause a gain-of-function mutation in ATN1.[6] Studies have supported the idea that mutated Atrophin-1 gathers in neurons and disrupts cell function.[7] The sequence of the ATN1 gene contains a nuclear localizing signal (NLS) and a nuclear export signal (NES).[7] It has been shown that a mutation of the NES in ATN1 can change where ATN1 localizes, and can cause aggregation to occur in the nucleus.[7] This can lead to an increase in cellular toxicity.[7]

Mutations in ATN1 are associated with a form of trinucleotide repeat disorder known as "dentatorubral-pallidoluysian atrophy" or "dentatorubropallidoluysian atrophy". Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia.[1] The disorder is related to the expansion of a trinucleotide repeat within this gene.[1] In patients with DRPLA, truncated ATN1 has been observed forming intranuclear aggregates that cause cell death.[7] The symptoms of this disorder can be credited to the significant reduction of brain and spinal tissue observed in those afflicted with DRPLA.[8] There are both juvenile-onset and late adult-onset variants of DRPLA, which show differing degrees of severity of specific symptoms.[8]

Interactions

ATN1 has been shown to interact with:

References

  1. ↑ 1.0 1.1 1.2 "ATN1 atrophin 1 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/1822. 
  2. ↑ "Entrez Gene: ATN1 atrophin 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1822. 
  3. ↑ 3.0 3.1 3.2 "Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription". The Journal of Cell Biology 150 (5): 939–48. September 2000. doi:10.1083/jcb.150.5.939. PMID 10973986. 
  4. ↑ "Atrophins' emerging roles in development and neurodegenerative disease". Cellular and Molecular Life Sciences 66 (3): 437–46. February 2009. doi:10.1007/s00018-008-8403-9. PMID 18953689. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 "ATN1 gene". Genetics Home Reference. https://ghr.nlm.nih.gov/gene/ATN1#normalfunction. 
  6. ↑ "Functional architecture of atrophins" (in en). The Journal of Biological Chemistry 282 (7): 5037–44. February 2007. doi:10.1074/jbc.M610274200. PMID 17150957. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 "Pathological accumulation of atrophin-1 in dentatorubralpallidoluysian atrophy". International Journal of Clinical and Experimental Pathology 4 (4): 378–84. April 2011. PMID 21577324. 
  8. ↑ 8.0 8.1 "Dentatorubral-Pallidoluysian Atrophy, DRPLA". http://themedicalbiochemistrypage.org/drpla.php. 
  9. ↑ "Dentatorubral-pallidoluysian atrophy protein interacts through a proline-rich region near polyglutamine with the SH3 domain of an insulin receptor tyrosine kinase substrate". Human Molecular Genetics 8 (6): 947–57. June 1999. doi:10.1093/hmg/8.6.947. PMID 10332026. 
  10. ↑ 10.0 10.1 10.2 "Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins". Molecular and Cellular Neurosciences 11 (3): 149–60. June 1998. doi:10.1006/mcne.1998.0677. PMID 9647693. 
  11. ↑ "Protein binding of a DRPLA family through arginine-glutamic acid dipeptide repeats is enhanced by extended polyglutamine". Human Molecular Genetics 9 (9): 1433–42. May 2000. doi:10.1093/hmg/9.9.1433. PMID 10814707. 

Further reading

External links



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