Human Gene ATXN2 (ENST00000535949.5) from GENCODE V44
  Description: Homo sapiens ataxin 2 (ATXN2), transcript variant 3, mRNA. (from RefSeq NM_001310123)
RefSeq Summary (NM_001310123): This gene belongs to a group of genes that is associated with microsatellite-expansion diseases, a class of neurological and neuromuscular disorders caused by expansion of short stretches of repetitive DNA. The protein encoded by this gene has two globular domains near the N-terminus, one of which contains a clathrin-mediated trans-Golgi signal and an endoplasmic reticulum exit signal. The encoded cytoplasmic protein localizes to the endoplasmic reticulum and plasma membrane, is involved in endocytosis, and modulates mTOR signals, modifying ribosomal translation and mitochondrial function. The N-terminal region of the protein contains a polyglutamine tract of 14-31 residues that can be expanded in the pathogenic state to 32-200 residues. Intermediate length expansions of this tract increase susceptibility to amyotrophic lateral sclerosis, while long expansions of this tract result in spinocerebellar ataxia-2, an autosomal-dominantly inherited, neurodegenerative disorder. Genome-wide association studies indicate that loss-of-function mutations in this gene may be associated with susceptibility to type I diabetes, obesity and hypertension. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016].
Gencode Transcript: ENST00000535949.5
Gencode Gene: ENSG00000204842.18
Transcript (Including UTRs)
   Position: hg38 chr12:111,452,754-111,599,673 Size: 146,920 Total Exon Count: 22 Strand: -
Coding Region
   Position: hg38 chr12:111,452,812-111,554,190 Size: 101,379 Coding Exon Count: 21 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:111,452,754-111,599,673)mRNA (may differ from genome)Protein (1006 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ATX2_HUMAN
DESCRIPTION: RecName: Full=Ataxin-2; AltName: Full=Spinocerebellar ataxia type 2 protein; AltName: Full=Trinucleotide repeat-containing gene 13 protein;
FUNCTION: Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.
SUBUNIT: Monomer (By similarity). Can also form homodimers (By similarity). Interacts with TARDBP; the interaction is RNA- dependent. Interacts with RBFOX1. Interacts with polyribosomes. Interacts with SH3GL2 and SH3GL3. Interacts with SH3KBP1 and CBL (By similarity). Interacts with EGFR.
INTERACTION: P54253:ATXN1; NbExp=4; IntAct=EBI-697691, EBI-930964; P11940:PABPC1; NbExp=3; IntAct=EBI-697691, EBI-81531; Q99962:SH3GL2; NbExp=4; IntAct=EBI-697691, EBI-77938; Q99963:SH3GL3; NbExp=7; IntAct=EBI-697691, EBI-473910;
SUBCELLULAR LOCATION: Cytoplasm (By similarity).
TISSUE SPECIFICITY: Expressed in the brain, heart, liver, skeletal muscle, pancreas and placenta. Isoform 1 is predominant in the brain and spinal cord. Isoform 4 is more abundant in the cerebellum. In the brain, broadly expressed in the amygdala, caudate nucleus, corpus callosum, hippocampus, hypothalamus, substantia nigra, subthalamic nucleus and thalamus.
POLYMORPHISM: The poly-Gln region of ATXN2 is polymorphic: 17 to 29 repeats are found in the normal population. Higher numbers of repeats result in different disease phenotypes depending on the length of the expansion.
DISEASE: Defects in ATXN2 are the cause of spinocerebellar ataxia type 2 (SCA2) [MIM:183090]; also known as olivopontocerebellar atrophy II (OPCA II or OPCA2). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA2 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA2 is characterized by hyporeflexia, myoclonus and action tremor and dopamine-responsive parkinsonism. Note=SCA2 is caused by expansion of a CAG repeat resulting in about 36 to 52 repeats in some patients. Longer expansions result in earlier the expansion, onset of the disease.
DISEASE: Defects in ATXN2 are a cause of susceptibility to amyotrophic lateral sclerosis type 13 (ALS13) [MIM:183090]. It is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Note=An increased risk for developing amyotrophic lateral sclerosis is seems to be conferred by CAG repeat intermediate expansions greater than 23 but below the threshold for developing spinocerebellar ataxia.
SIMILARITY: Belongs to the ataxin-2 family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ATXN2";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: ATXN2
Diseases sorted by gene-association score: spinocerebellar ataxia 2* (1472), parkinson disease, late-onset* (292), atxn2-related parkinson disease susceptibility* (100), parkinson disease susceptibility* (58), machado-joseph disease (17), olivopontocerebellar atrophy (17), spinocerebellar ataxia 7 (16), autosomal dominant cerebellar ataxia (13), spinocerebellar ataxia 36 (11), lateral sclerosis (11), dentatorubro-pallidoluysian atrophy (10), hereditary ataxia (9), spinocerebellar degeneration (9), cerebellar ataxia (8), ataxia (8), spinocerebellar ataxia 12 (7), spastic paraplegia 36, autosomal dominant (7), amyotrophic lateral sclerosis 1* (6), hereditary motor and sensory neuropathy, type iic (5), cerebellar disease (4), frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (4), obesity (2), dementia, frontotemporal (1), retinitis pigmentosa (0)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 13.19 RPKM in Brain - Cerebellum
Total median expression: 422.18 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -24.80126-0.197 Picture PostScript Text
3' UTR -9.9058-0.171 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009818 - Ataxin-2_C
IPR010920 - LSM_dom
IPR009604 - LsmAD_domain
IPR025852 - SM_dom_ATX
IPR013771 - Trypsin/amylase_inhib

Pfam Domains:
PF06741 - LsmAD domain
PF07145 - Ataxin-2 C-terminal region
PF14438 - Ataxin 2 SM domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3KTR - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q99700
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0005154 epidermal growth factor receptor binding
GO:0005515 protein binding
GO:0008022 protein C-terminus binding

Biological Process:
GO:0002091 negative regulation of receptor internalization
GO:0006417 regulation of translation
GO:0010603 regulation of cytoplasmic mRNA processing body assembly
GO:0016070 RNA metabolic process
GO:0033962 cytoplasmic mRNA processing body assembly
GO:0034063 stress granule assembly
GO:0050658 RNA transport

Cellular Component:
GO:0005737 cytoplasm
GO:0005794 Golgi apparatus
GO:0005802 trans-Golgi network
GO:0005829 cytosol
GO:0005844 polysome
GO:0010494 cytoplasmic stress granule
GO:0016020 membrane
GO:0048471 perinuclear region of cytoplasm
GO:1990904 ribonucleoprotein complex


-  Descriptions from all associated GenBank mRNAs
  Y08262 - H.sapiens mRNA for SCA2 protein.
U70323 - Human ataxin-2 (SCA2) mRNA, complete cds.
BC111757 - Homo sapiens ataxin 2, mRNA (cDNA clone IMAGE:40027338), partial cds.
BC114546 - Homo sapiens ataxin 2, mRNA (cDNA clone MGC:133091 IMAGE:40027340), complete cds.
AK307803 - Homo sapiens cDNA, FLJ97751.
AK095017 - Homo sapiens cDNA FLJ37698 fis, clone BRHIP2015679, highly similar to Ataxin-2.
AK126309 - Homo sapiens cDNA FLJ44330 fis, clone TRACH3003547.
AK128613 - Homo sapiens cDNA FLJ46772 fis, clone TRACH3026283, moderately similar to Homo sapiens spinocerebellar ataxia 2 (olivopontocerebellar ataxia 2, autosomal dominant, ataxin 2) (SCA2).
JD115364 - Sequence 96388 from Patent EP1572962.
JD484562 - Sequence 465586 from Patent EP1572962.

-  Other Names for This Gene
  Alternate Gene Symbols: A6NLD4, ATX2, ATX2_HUMAN, ENST00000535949.1, ENST00000535949.2, ENST00000535949.3, ENST00000535949.4, NM_001310123, Q6ZQZ7, Q99493, Q99700, SCA2, TNRC13, uc001tsi.1, uc001tsi.2, uc001tsi.3, uc001tsi.4
UCSC ID: ENST00000535949.5
RefSeq Accession: NM_001310123
Protein: Q99700 (aka ATX2_HUMAN)
CCDS: CCDS81738.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ATXN2:
ataxias (Hereditary Ataxia Overview)
sca2 (Spinocerebellar Ataxia Type 2)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.