Ataxin-2 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''ATXN2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. Mutations in ATXN2 cause

spinocerebellar ataxia Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of s ...

type 2 (SCA2).

Protein structure

Ataxin-2 contains the following protein domains: * Two

LSm In molecular biology, LSm proteins are a family of RNA-binding proteins found in virtually every cellular organism. LSm is a contraction of 'like Sm', because the first identified members of the LSm protein family were the Sm proteins. LSm pro ...

domains, which likely allow it to bind RNA * A PAM2 motif, predicted to associate with the

poly(A)-binding protein Poly(A)-binding protein (PAB or PABP) is an RNA-binding protein which triggers the binding of eukaryotic initiation factor 4 complex (eIF4G) directly to the poly(A) tail of mRNA which is 200-250 nucleotides long. The poly(A) tail is located on the ...

* A

polyglutamine tract A polyglutamine tract or polyQ tract is a portion of a protein consisting of a sequence of several glutamine units. A tract typically consists of about 10 to a few hundred such units. A multitude of genes, in various eukaryotic species (including h ...

in some species (located near the amino terminal in primates and between the LSm domains in insects) A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain.

Species, tissue, and subcellular distribution

''ATXN2'' is conserved across

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

s. Most vertebrates have two

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

of the gene (called ''ATXN2'' and ''

ATXN2L Ataxin-2-like protein was initially identified in 1996 and designated Ataxin-2 Related protein (A2RP) as the search for the gene causing SCA2 lead to the identification of 2 cDNA clones with high similarity to ATXN2 (Pulst et al, 1996). It was lat ...

'' in humans), with the exception of birds which only have one. Plant species have two to six ''ATXN2'' orthologs. ''ATXN2'' is ubiquitously expressed in different tissues. Within individual cells, it localizes to the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...

and

stress granule Stress granules are dense aggregations in the cytosol composed of proteins and RNAs that appear when the cell is under stress. The RNA molecules stored are stalled translation pre-initiation complexes: failed attempts to make protein from mRNA. St ...

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

s and

P-bodies P-bodies, or processing bodies are distinct foci formed by phase separation within the cytoplasm of the eukaryotic cell consisting of many enzymes involved in mRNA turnover. P-bodies are highly conserved structures and have been observed in soma ...

, which also play roles in RNA regulation.

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

type 2 (SCA2), a fatal progressive genetic disorder in which neurons

degenerate Degeneracy, degenerate, or degeneration may refer to: Arts and entertainment * Degenerate (album), ''Degenerate'' (album), a 2010 album by the British band Trigger the Bloodshed * Degenerate art, a term adopted in the 1920s by the Nazi Party i ...

in the

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

inferior olive The inferior olivary nucleus (ION), is a structure found in the medulla oblongata underneath the superior olivary nucleus.Gado, Thomas A. Woolsey; Joseph Hanaway; Mokhtar H. (2003). The brain atlas a visual guide to the human central nervous syste ...

pons The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of Va ...

, and other areas. Symptoms of SCA2 include

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

(a loss of coordinated movements),

parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lewy bo ...

, and dementia in some cases. 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 The University of Pennsylvania (also known as Penn or UPenn) is a private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest-regarded universitie ...

discovered that intermediate-size CAG repeat expansions are significantly associated with risk for developing

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

(Lou Gehrig's disease).

References

External links

GeneReviews/NIH/NCBI/UW entry on Spinocerebellar Ataxia Type 2
* {{UCSC gene info, ATXN2