The ASNSD1 locus is bicistronic, producing both a microprotein, ASDURF, from an upstream ORF in its 5' UTR and the downstream ASNSD1 protein from the main CDS [PMID:31738558, PMID:40058972]. ASDURF is the 12th subunit of the PAQosome, assembling via β-prefoldin structural homology with the five subunits of the prefoldin-like module to form a heterohexameric chaperone complex PMID:31738558, and through this complex it promotes medulloblastoma cell survival in a manner associated with MYC-family oncogenes [PMID:38176414, PMID:37205492]. The downstream ASNSD1 protein supports skeletal muscle maintenance, as its inactivation in mice produces a progressive degenerative myopathy with sarcopenia and replacement of muscle by adipose tissue PMID:32638637. ASNSD1 (NS3TP1) also acts in hepatic stellate cells, where it engages TGFβ1/Smad3 and NF-κB signaling — Smad3 and p65 bind ASNSD1, p65 activates the ASNSD1 promoter, and ASNSD1 enhances TGFβ1 receptor I promoter activity — to promote stellate cell activation and hepatic fibrosis PMID:37274069. Despite the annotated asparagine synthetase domain implied by its name, no catalytic enzymatic activity for the ASNSD1 protein has been characterized in the available corpus.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2019 | High | ASDURF, encoded by an upstream open reading frame (uORF) in the 5' UTR of ASNSD1 mRNA, is the 12th subunit of the PAQosome chaperone complex. It displays structural homology to β-prefoldins and assembles with the five known subunits of the prefoldin-like module of the PAQosome to form a heterohexameric prefoldin-like complex. | PMID:31738558 | Journal of proteome research |
| 2024 | High | The ASNSD1-uORF microprotein (ASDURF) promotes medulloblastoma cell survival through engagement with the prefoldin-like chaperone complex, and its expression is associated with MYC-family oncogenes. | PMID:38176414, PMID:37205492 | Molecular cell |
| 2020 | Medium | Inactivation of ASNSD1 in mice causes a progressive degenerative myopathy with sarcopenia, myosteatosis, and extensive replacement of muscle by adipose tissue, establishing a functional role for ASNSD1 in skeletal muscle maintenance. | PMID:32638637 | Veterinary pathology |
| 2023 | Medium | NS3TP1/ASNSD1 promotes activation, proliferation, and differentiation of hepatic stellate cells (HSCs) and enhances hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways. Both Smad3 and p65 were shown to bind NS3TP1 by co-immunoprecipitation, and p65 increased NS3TP1 promoter activity while NS3TP1 increased TGFβ1 receptor I promoter activity. | PMID:37274069 | World journal of gastroenterology |
| 2023 | Low | Aspartate upregulates NS3TP1/ASNSD1 expression in vivo and in vitro, and NS3TP1 exerts an inhibitory effect on liver fibrosis by suppressing the NF-κB/NLRP3 signaling pathway. | PMID:36983568 | Journal of personalized medicine |
| 2023 | Low | ASDURF (the ASNSD1-uORF product) promotes hepatic fibrosis through TGFβ1/Smad3 and NF-κB signaling pathways and regulates the expression of the downstream ASNSD1 protein. Other PAQosome subunits (PFDN4, PFDN5, URI1, UXT) regulate cell proliferation through the PI3K/AKT pathway. | PMID:38016755 | Journal of gastroenterology and hepatology |
| 2025 | Low | The ASNSD1 mRNA gives rise to a bicistronic transcript in which both the upstream sORF (encoding ASDURF) and the downstream CDS (encoding ASNSD1 protein) are translated; the translation regulation of this unusual genetic arrangement was discussed in the context of functional genomics findings. | PMID:40058972 | Biochemistry. Biokhimiia |