Ataxin-2

Ataxin-2 is a protein that in humans is encoded by the ATXN2 gene.^[5][6] Mutations in ATXN2 cause spinocerebellar ataxia type 2 (SCA2).

ATXN2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3KTR
Identifiers
Aliases	ATXN2, ASL13, ATX2, SCA2, TNRC13, ataxin 2
External IDs	OMIM: 601517; MGI: 1277223; HomoloGene: 2234; GeneCards: ATXN2; OMA:ATXN2 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.12 Start 111,443,485 bp[1] End 111,599,676 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 F Start 121,711,337 bp[2] End 121,816,493 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell epithelium of colon olfactory bulb sural nerve ventricular zone gonad right uterine tube C1 segment right hemisphere of cerebellum right ovary Top expressed in internal carotid artery genital tubercle tail of embryo neural layer of retina external carotid artery Ileal epithelium zygote cumulus cell secondary oocyte Rostral migratory stream More reference expression data BioGPS More reference expression data
Gene ontology Molecular function epidermal growth factor receptor binding protein C-terminus binding protein binding RNA binding Cellular component cytoplasm perinuclear region of cytoplasm polysome trans-Golgi network Golgi apparatus cytoplasmic stress granule membrane cytosol ribonucleoprotein complex Biological process regulation of cytoplasmic mRNA processing body assembly stress granule assembly RNA metabolic process regulation of translation P-body assembly RNA transport negative regulation of receptor internalization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6311 20239 Ensembl ENSG00000204842 ENSMUSG00000042605 UniProt Q99700 O70305 RefSeq (mRNA) NM_001310121 NM_001310123 NM_002973 NM_001372574 NM_009125 NM_001359153 RefSeq (protein) NP_001297050 NP_001297052 NP_002964 NP_001359503 NP_033151 NP_001346082 Location (UCSC) Chr 12: 111.44 – 111.6 Mb Chr 5: 121.71 – 121.82 Mb PubMed search [3] [4]
Wikidata
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Protein structure

Ataxin-2 contains the following protein domains:^[7]

• Two LSm domains, which likely allow it to bind RNA
• A PAM2 motif, predicted to associate with the poly(A)-binding protein
• A polyglutamine tract in some species (located near the amino terminal in primates and between the LSm domains in insects)^[8]

A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain.^[9]

Species, tissue, and subcellular distribution

ATXN2 is conserved across eukaryotes. Most vertebrates have two orthologs of the gene (called ATXN2 and ATXN2L in humans), with the exception of birds which only have one. Plant species have two to six ATXN2 orthologs.^[8]

ATXN2 is ubiquitously expressed in different tissues. Within individual cells, it localizes to the Golgi apparatus and stress granules.^[10]

Function

Ataxin-2 is involved in regulating mRNA translation through its interactions with the poly(A)-binding protein. It is also involved in the formation of stress granules and P-bodies, which also play roles in RNA regulation.^[10]

Clinical significance

Spinocerebellar ataxia type 2 (SCA2)

The polyglutamine tract in human ataxin-2 is unstable and can expand as it is transmitted across generations. Normal alleles usually have 22 or 23 repeats, but can contain up to 31 repeats. Longer expansions can cause spinocerebellar ataxia type 2 (SCA2), a fatal progressive genetic disorder in which neurons degenerate in the cerebellum, inferior olive, pons, and other areas. Symptoms of SCA2 include ataxia (a loss of coordinated movements), parkinsonism, and dementia in some cases.^[11] The disease allele usually contains 34-52 CAG repeats, but can contain as few as 32 or more than 100, and can expand in size when transmitted to successive generations. How the polyglutamine expansion in ataxin-2 leads to these symptoms is unknown.

Amyotrophic lateral sclerosis (ALS)

In 2010, work from Aaron Gitler and Nancy Bonini at the University of Pennsylvania discovered that intermediate-size CAG repeat expansions are significantly associated with risk for developing amyotrophic lateral sclerosis (Lou Gehrig's disease).^[12]

Primary open-angle glaucoma (POAG) and intraocular pressure (IOP)

Genome-wide association studies have revealed a significant association of ATXN2 variants with POAG and IOP. Further investigation of the genetic and biological mechanisms underlying the association between ATXN2 and POAG could provide valuable insights into the pathogenesis and potential therapeutic targets for glaucoma.^[13]