|Detection of Human Ubiquilin 1 by Western Blot. Western blot shows lysates of TT human medullary thyroid cancer cell line, IMR‑32 human neuroblastoma cell line, and PC‑3 human prostate cancer cell line. PVDF membrane was probed with 2 µg/mL of Sheep Anti-Human Ubiquilin 1 Antigen Affinity-purified Polyclonal Antibody (Catalog # AF7969) followed by HRP-conjugated Anti-Sheep IgG Secondary Antibody (Catalog # HAF016). A specific band was detected for Ubiquilin 1 at approximately 65-70 kDa (as indicated). This experiment was conducted under reducing conditions and using Immunoblot Buffer Group 1.|
Ubiquilin-1 (also known as DA41 and PLIC-1/Protein Linking IAP with Cytoskeleton 1) is a 62-70 kDa intracellular member of the UBL-UBA family of proteins. Consistent with its name, it ubiquitously expressed, and is particularly prominent in skeletal muscle and neurons. Multiple functions have been attributed to ubiquilin-1. For instance, it is now known to be a key player in APP processing. On the cleavage side, ubiquilin-1 binds to PS/presenilin, a component of the gamma -secretase complex that cleaves APP. Ubiquilin-1 appears to target both ubiquitinated single chain PS to the proteosome, and aggregated PS to the aggresome. With respect to APP, ubiquilin-1 serves as a molecular chaperone, binding to and inhibiting APP aggregation. On cells expressing CD47, Ubiquilin-1 acts as an intermediary between integrins, the cytoskeleton and CD47, promoting cell spreading. And in neurons, ubiquilin-1 stabilizes both membrane and GABA subunit stability, enhancing inhibitory synaptic transmission. Human ubiquilin-1 is 589 amino acids (aa) in length. It contains one ubiquitin-like domain (aa 37-111), an S5a binding site (aa 72-105) and a UBA binding region (aa 548-585). There are multiple splice variants, ranging from 19-59 kDa in size. One shows a deletion of aa 418-445, a second contains a three aa substitution for aa 151-589, a third possesses a 29 aa substitution for aa 112-589, and a fourth shows a deletion of aa 61-237 coupled to a second deletion of aa 361‑589. Over aa 546-585, human and mouse ubiquilin-1 are identical in amino acid sequence.