UBXN1
Description
The UBXN1 (UBX domain protein 1) is a protein-coding gene located on chromosome 11.
UBXN1, also known as SAPK substrate protein 1 or UBA/UBX 33.3 kDa protein, is a ubiquitin-binding protein. It plays a role in modulating the innate immune response. UBXN1 blocks both the RIG-I-like receptors (RLR) and NF-kappa-B pathways. Following viral infection, it is induced and recruited to the RLR component MAVS. UBXN1 interferes with MAVS oligomerization, disrupting the MAVS/TRAF3/TRAF6 signalosome. This serves as a brake to prevent excessive RLR signaling. UBXN1 also interacts with cellular inhibitors of apoptosis proteins (cIAPs), inhibiting their recruitment to TNFR1 and interfering with the TNFalpha-triggered NF-kappa-B pathway. UBXN1 associates with CUL1, inhibiting the degradation of NF-kappa-B inhibitor alpha/NFKBIA and preventing NF-kappa-B activation. It interacts with the BRCA1-BARD1 heterodimer, regulating its activity. UBXN1 specifically binds 'Lys-6'-linked polyubiquitin chains and inhibits the E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer when interacting with autoubiquitinated BRCA1. UBXN1 is a component of a complex required for coupling deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol. It interacts with MAVS, CUL1, BIRC2/c-IAP1, VCP, BRCA1, and BARD1. Its C-terminal UBX domain interacts with nipah virus protein V.
UBXN1, also known as SAPK substrate protein 1 or UBA/UBX 33.3 kDa protein, is a ubiquitin-binding protein that plays a crucial role in modulating the innate immune response. It functions as a negative regulator, inhibiting both the RIG-I-like receptor (RLR) and NF-κB signaling pathways. Following viral infection, UBXN1 is induced and recruited to MAVS, a key component of the RLR pathway. This interaction disrupts MAVS oligomerization and the MAVS/TRAF3/TRAF6 signalosome, effectively dampening excessive RLR signaling. UBXN1 also interferes with the TNFα-triggered NF-κB pathway by interacting with cellular inhibitors of apoptosis proteins (cIAPs), preventing their recruitment to TNFR1. Additionally, UBXN1 associates with CUL1, inhibiting the degradation of NF-κB inhibitor alpha (NFKBIA), which remains bound to NF-κB, thereby preventing NF-κB activation. UBXN1 interacts with the BRCA1-BARD1 heterodimer, regulating its activity. Specifically, it binds Lys-6-linked polyubiquitin chains and interacts with autoubiquitinated BRCA1, inhibiting the E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer. Furthermore, UBXN1 is part of a complex involved in the deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated into the cytosol.
UBXN1 is also known as 2B28, SAKS1, UBXD10.
Associated Diseases
- hemoglobin E-beta-thalassemia syndrome
- dehydrated hereditary stomatocytosis
- microcytic anemia with liver iron overload
- hemoglobin D disease
- IRIDA syndrome
- hemoglobin E disease
- familial pseudohyperkalemia
- overhydrated hereditary stomatocytosis
- monosomy 7 myelodysplasia and leukemia syndrome 1
- hereditary elliptocytosis
- sideroblastic anemia 3
- severe congenital hypochromic anemia with ringed sideroblasts
