SETX

Probable helicase senataxin is an enzyme that in humans is encoded by the SETXgene.[5][6][7]

For the region of the U.S. state, see Southeast Texas.
SETX
Identifiers
Aliases SETX, ALS4, AOA2, SCAR1, bA479K20.2, senataxin, Sen1, SCAN2
External IDs OMIM: 608465MGI: 2443480HomoloGene: 41003GeneCards: SETX
Gene location (Human)
Chr. Chromosome 9 (human)[1]

Band 9q34.13 Start 132,261,356 bp[1]
End 132,354,986 bp[1]
Gene location (Mouse)
Chr. Chromosome 2 (mouse)[2]

Band 2|2 B Start 29,124,181 bp[2]
End 29,182,471 bp[2]
RNA expression pattern
Bgee
Top expressed in
  • testicle
  • lung
  • corpus callosum
  • Achilles tendon
  • kidney
  • stomach
  • heart
More reference expression data
BioGPS

More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
Species Human Mouse
Entrez

23064

269254

Ensembl

ENSG00000107290

ENSMUSG00000043535

UniProt

Q7Z333

A2AKX3

RefSeq (mRNA)

NM_015046
NM_001351527
NM_001351528

NM_198033

RefSeq (protein)

NP_055861
NP_001338456
NP_001338457

NP_932150

Location (UCSC) Chr 9: 132.26 – 132.35 Mb Chr 2: 29.12 – 29.18 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

This gene encodes a protein named senataxin, a 302kDa protein[8]

. . . SETX . . .

There is high homology between human SETX and yeast Sen1. Sen1 in yeast is a RNA/DNA helicase and the highly conserved sequences between these genes, particularly in the helicase domain, indicates that SETX in humans may have similar roles in gene expression and maintaining genome stability. In Sen1, the N-terminus has shown interactions with the C-terminal domain of RNA polymerase II, ribonuclease III, and NER factor Rad2/XPG. Meanwhile, the C-terminus encodes the DNA/RNA helicase activity.[9] Similarly, SETX encodes the senataxin protein that has a N-terminal that is likely to be involved with interacting with other proteins. Senataxin interacts with RNA polymerase II and poly(A) binding proteins. At the C-terminal, senataxin has a DEAD box helicase domain.[10]

Although senataxin is widely expressed in many tissues in the body, the cellular roles of senataxin are not completely understood. However, based on current research and examining homologs of SETX, senataxin is thought to play an important role in resolving R-loops, transcription termination, and maintaining genome stability by being an essential component of the DNA-damage response (DDR).[11]

SETX is suspected to be involved in DNA damage repair and maintaining genome stability by working with other proteins in the DNA damage response. R loops may arise from replication stress, such as when transcription and replication occur at the same time at a certain loci. This often occurs when transcribing long genes since transcription of that gene can take longer than one round of replication. When the replisome and transcription machinery collide, R loops can form and double stranded breaks can form.[12] At these collision sites, SETX was shown to co-localize with 53BP1, which is a marker for DNA damage.[13] Furthermore, SETX was observed to promote homologous recombination repair and prevent translocation.[14] To further support SETX’s role in DNA damage repair, SETX co-localizes with many other DDR factors. For example, BRCA1 was also shown to recruit SETX to remove R-loops, which prevents DNA mutations that arise as a result of the vulnerable single stranded DNA that is part of the R-loop structure.[15] SETX may be involved in double strand break repair through its involvement in loading RAD51, which is a crucial protein in double strand break repair through homologous recombination.[16]

Furthermore, Senataxin may be involved in transcription termination. A large amount of R-loops are found at the 3’ end of some mammalian genes, after poly-adenylation sites. The R-loops are thought to be involved in transcription termination by stalling RNA polymerase II. The senataxin protein, which has RNA-DNA helicase activity, and DHX9 human helicase can resolve R-loops. This allows XRN2, an exonuclease, to access the 3’ cleavage polyadenylated sites and degrade the 3’ transcript. This ultimately leads to termination of transcription.[17]

. . . SETX . . .

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. . . SETX . . .

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