ASB10 is a substrate-recognition E3 ubiquitin ligase that controls the abundance of specific client proteins and thereby regulates tissue homeostasis in the eye, vasculature, and heart [PMID:34285210, PMID:40399264]. As an E3 ligase it ubiquitylates the tumor endothelial marker TEM8, targeting it for proteasomal degradation so that loss of ASB10 elevates homeostatic TEM8 levels PMID:34285210. In the heart, ASB10 acts in the opposite direction on a different client: it binds HSP70 and competitively blocks STUB1-mediated ubiquitination of HSP70, stabilizing HSP70 and driving inflammation and accumulation of Ser394-phosphorylated HDAC2, which together exacerbate pressure-overload cardiac hypertrophy and fibrosis PMID:40399264. In trabecular meshwork cells ASB10 localizes to intracellular vesicles where it physically associates with HSP70 and with proteasomal (20S α4 subunit) and autophagic-lysosomal machinery, and its vesicle dynamics track autophagic flux, while ASB10 itself is not ubiquitinated PMID:23901248; silencing ASB10 reduces aqueous humor outflow facility, and a splice-altering coding variant links ASB10 to primary open-angle glaucoma PMID:22156576. A unified enzymatic mechanism connecting substrate selection across these tissues to a single biochemical activity has not been fully resolved in the available corpus.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2011 | Medium | ASB10 silencing in perfused anterior segment organ culture reduced aqueous humor outflow facility by ~50% compared with control-infected anterior segments, demonstrating a functional role for ASB10 in trabecular meshwork outflow regulation. | PMID:22156576 | Human molecular genetics |
| 2011 | Medium | ASB10 mRNA and protein are strongly expressed in trabecular meshwork, retinal ganglion cells, and ciliary body, as established by expression analysis in human ocular tissues. | PMID:22156576 | Human molecular genetics |
| 2011 | Medium | A synonymous variant c.765C>T (Thr255Thr) in ASB10 affects an exon splice enhancer site and alters mRNA splicing in lymphoblasts of affected family members with POAG. | PMID:22156576 | Human molecular genetics |
| 2013 | Medium | ASB10 localizes to intracellular vesicular structures in human trabecular meshwork (HTM) cells and co-localizes with markers of the ubiquitin-proteasomal pathway (ubiquitin, α4 subunit of 20S proteasome) and autophagic structures (LC3, p62, HDAC6, HSP70, Rab7, LAMP1), as shown by confocal and super-resolution structured illumination microscopy. | PMID:23901248 | Molecular vision |
| 2013 | Medium | ASB10 physically interacts with HSP70 and with the α4 subunit of the 20S proteasome in HTM cells, as demonstrated by co-immunoprecipitation. | PMID:23901248 | Molecular vision |
| 2013 | Medium | ASB10 itself is not ubiquitinated, despite its association with ubiquitin-mediated degradation pathway components in HTM cells. | PMID:23901248 | Molecular vision |
| 2013 | Medium | Treatment of HTM cells with the autophagy/proteasome inhibitor MG132 significantly increased the number of small ASB10-stained vesicles, while autophagy inhibitors (wortmannin, bafilomycin A1) decreased them, indicating ASB10 vesicle dynamics are coupled to autophagic flux. | PMID:23901248 | Molecular vision |
| 2021 | Medium | ASB10 functions as an E3 ubiquitin ligase that ubiquitylates TEM8 (tumor endothelial marker 8) for proteasomal degradation; ASB10 deficiency in triple-negative breast cancer results in elevated homeostatic TEM8 levels. | PMID:34285210 | Nature communications |
| 2025 | High | Asb10 binds HSP70 and competitively blocks STUB1-mediated ubiquitination and proteasomal degradation of HSP70, thereby stabilizing HSP70 protein levels and exacerbating cardiac hypertrophic growth. | PMID:40399264 | Cell death & disease |
| 2025 | High | Asb10 overexpression in vivo (AAV9-Asb10) worsens cardiac function and increases interstitial fibrosis after transverse aortic constriction (TAC), while Asb10 knockdown (AAV9-shAsb10) improves outcomes, establishing Asb10 as a pro-hypertrophic factor in pressure-overload heart failure. | PMID:40399264 | Cell death & disease |
| 2025 | Medium | The pro-hypertrophic effects of Asb10 are mediated through HSP70 stabilization leading to cardiac inflammation and activation of phospho-HDAC2 at Ser394 (pHDAC2S394). | PMID:40399264 | Cell death & disease |