Seroatlas · Human Serome Atlas

ATXN2

Ataxin-2

Also known as: ATX2, ATX2_HUMAN, SCA2, TNRC13

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q99700
Gene: ATXN2
Ensembl: ENSG00000204842
Chromosome: 12
Canonical length: 1313 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location: Cytosol
Quaternary structure: Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1313 residues, UniProt reviewed canonical sequence.

>Q99700|ATXN2
     1  MRSAAAAPRS PAVATESRRF AAARWPGWRS LQRPARRSGR GGGGAAPGPY PSAAPPPPGP
    61  GPPPSRQSSP PSASDCFGSN GNGGGAFRPG SRRLLGLGGP PRPFVVLLLP LASPGAPPAA
   121  PTRASPLGAR ASPPRSGVSL ARPAPGCPRP ACEPVYGPLT MSLKPQQQQQ QQQQQQQQQQ
   181  QQQQQQQQPP PAAANVRKPG GSGLLASPAA APSPSSSSVS SSSATAPSSV VAATSGGGRP
   241  GLGRGRNSNK GLPQSTISFD GIYANMRMVH ILTSVVGSKC EVQVKNGGIY EGVFKTYSPK
   301  CDLVLDAAHE KSTESSSGPK REEIMESILF KCSDFVVVQF KDMDSSYAKR DAFTDSAISA
   361  KVNGEHKEKD LEPWDAGELT ANEELEALEN DVSNGWDPND MFRYNEENYG VVSTYDSSLS
   421  SYTVPLERDN SEEFLKREAR ANQLAEEIES SAQYKARVAL ENDDRSEEEK YTAVQRNSSE
   481  REGHSINTRE NKYIPPGQRN REVISWGSGR QNSPRMGQPG SGSMPSRSTS HTSDFNPNSG
   541  SDQRVVNGGV PWPSPCPSPS SRPPSRYQSG PNSLPPRAAT PTRPPSRPPS RPSRPPSHPS
   601  AHGSPAPVST MPKRMSSEGP PRMSPKAQRH PRNHRVSAGR GSISSGLEFV SHNPPSEAAT
   661  PPVARTSPSG GTWSSVVSGV PRLSPKTHRP RSPRQNSIGN TPSGPVLASP QAGIIPTEAV
   721  AMPIPAASPT PASPASNRAV TPSSEAKDSR LQDQRQNSPA GNKENIKPNE TSPSFSKAEN
   781  KGISPVVSEH RKQIDDLKKF KNDFRLQPSS TSESMDQLLN KNREGEKSRD LIKDKIEPSA
   841  KDSFIENSSS NCTSGSSKPN SPSISPSILS NTEHKRGPEV TSQGVQTSSP ACKQEKDDKE
   901  EKKDAAEQVR KSTLNPNAKE FNPRSFSQPK PSTTPTSPRP QAQPSPSMVG HQQPTPVYTQ
   961  PVCFAPNMMY PVPVSPGVQP LYPIPMTPMP VNQAKTYRAV PNMPQQRQDQ HHQSAMMHPA
  1021  SAAGPPIAAT PPAYSTQYVA YSPQQFPNQP LVQHVPHYQS QHPHVYSPVI QGNARMMAPP
  1081  THAQPGLVSS SATQYGAHEQ THAMYACPKL PYNKETSPSF YFAISTGSLA QQYAHPNATL
  1141  HPHTPHPQPS ATPTGQQQSQ HGGSHPAPSP VQHHQHQAAQ ALHLASPQQQ SAIYHAGLAP
  1201  TPPSMTPASN TQSPQNSFPA AQQTVFTIHP SHVQPAYTNP PHMAHVPQAH VQSGMVPSHP
  1261  TAHAPMMLMT TQPPGGPQAA LAQSALQPIP VSTTAHFPYM THPSVQAHHQ QQL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATXN2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.66
Highest tissue expression: 28 nTPM

Expression across tissuesHPA

Tissue

cerebellum: 28 nTPM
spinal cord: 28 nTPM
skeletal muscle: 27 nTPM
cerebral cortex: 26 nTPM
ovary: 25 nTPM
blood vessel: 25 nTPM

Single-cell type

sertoli cells: 528 nCPM
podocytes: 477 nCPM
choroid plexus epithelial cells: 471 nCPM
ependymal cells: 452 nCPM
thyrotrophs: 374 nCPM
proximal tubule cells: 362 nCPM

Immune cell

non-classical monocyte: 6.5 nTPM
eosinophil: 5.8 nTPM
NK-cell: 5.6 nTPM
memory CD8 T-cell: 5.3 nTPM
MAIT T-cell: 5.2 nTPM
memory B-cell: 5.1 nTPM

Brain region

cerebral cortex: 84 nTPM
hypothalamus: 70 nTPM
midbrain: 64 nTPM
medulla oblongata: 61 nTPM
white matter: 61 nTPM
pons: 60 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATXN2.

Disease | AllUniProt

Conditions ATXN2 is implicated in, by any mechanism.

Spinocerebellar ataxia 2 (SCA2) MIM:183090
Amyotrophic lateral sclerosis 13 (ALS13) MIM:183090

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 237 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.33
gnomAD pLI: 0.85
gnomAD missense Z: 2.35
DepMap mean gene effect: -0.21
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ATXN2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ATXN2 as an antibody target. Whether an autoantibody or antibody against ATXN2 could matter depends on whether native ATXN2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ATXN2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label ATXN2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Loading the interactive Seroatlas protein explorer...