UBX domain-containing protein 1 (UBXN1)
The protein contains 297 amino acids for an estimated molecular weight of 33325 Da.
Ubiquitin-binding protein that plays a role in the modulation of innate immune response. Blocks both the RIG-I-like receptors (RLR) and NF-kappa-B pathways. Following viral infection, UBXN1 is induced and recruited to the RLR component MAVS. In turn, interferes with MAVS oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. This function probably serves as a brake to prevent excessive RLR signaling (PubMed:23545497). Interferes with the TNFalpha-triggered NF-kappa-B pathway by interacting with cellular inhibitors of apoptosis proteins (cIAPs) and thereby inhibiting their recruitment to TNFR1 (PubMed:25681446). Prevents also the activation of NF-kappa-B by associating with CUL1 and thus inhibiting NF-kappa-B inhibitor alpha/NFKBIA degradation that remains bound to NF-kappa-B (PubMed:28152074). Interacts with the BRCA1-BARD1 heterodimer and regulates its activity. Specifically binds 'Lys-6'-linked polyubiquitin chains. Interaction with autoubiquitinated BRCA1 leads to the inhibition of the E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer (PubMed:20351172). Component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol. (updated: Nov. 22, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs11543359 |
Biological Process
Double-strand break repair
Negative regulation of ERAD pathway
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Negative regulation of protein K48-linked deubiquitination
Negative regulation of protein ubiquitination
Negative regulation of ubiquitin-specific protease activity
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein folding
Viral process
Cellular Component
Cytoplasm
Cytosol
Dendrite
Endoplasmic reticulum
Neuronal cell body
Nucleoplasm
Nucleus
VCP-NPL4-UFD1 AAA ATPase complex
Molecular Function
ATPase binding
K48-linked polyubiquitin modification-dependent protein binding
K6-linked polyubiquitin modification-dependent protein binding
Polyubiquitin modification-dependent protein binding
Proteasome regulatory particle binding
Ubiquitin binding
Ubiquitin protein ligase binding
The reference OMIM entry for this protein is 616378
Ubx domain protein 1; ubxn1
Sapk substrate protein 1; saks1
DESCRIPTION
UBXN1 contains a ubiquitin-binding UBA domain and a UBX motif that adopts a 3-dimensional fold similar to ubiquitin (191339). UBXN1 regulates the enzymatic function of BRCA1 (113705) in a ubiquitin-dependent manner (Wu-Baer et al., 2010). It also modulates antiviral signaling by targeting MAVS (609676) in a ubiquitin-independent manner (Wang et al., 2013).CLONING
BRCA1 forms a heterodimer with BARD1 (601593) in vivo that has E3 ubiquitin ligase activity. Using a yeast 2-hybrid screen of a human lymphocyte cDNA library with the N terminus of BRCA1 fused with full-length BARD1 as bait, Wu-Baer et al. (2010) obtained a cDNA encoding UBXN1. The predicted 297-amino acid UBXN1 protein contains an N-terminal UBA domain and a C-terminal UBX motif.GENE FUNCTION
Using immunoprecipitation and immunoblot analyses, Wu-Baer et al. (2010) confirmed interaction of human UBXN1 with BRCA1 and BARD1. UBXN1 could also interact with the N terminus of BRCA1 alone, but the presence of BARD1 enhanced the interaction. The C-terminal portion of UBXN1 was involved in interaction of UBXN1 with BRCA1, and the N-terminal UBA domain of UBXN1 bound lys6-linked polyubiquitin chains conjugated to BRCA1. UBXN1 inhibited the E3 ligase activity of BRCA1/BARD1, and this inhibition depended on the ubiquitin-binding activity of UBXN1. Wu-Baer et al. (2010) proposed that UBXN1 regulates the enzymatic function of BRCA1 in a ubiquitination status-dependent manner. Using a small interfering RNA screen, Wang et al. (2013) found that human UBXN1 exhibited the strongest inhibitory effect on RNA-virus-induced interferon promoter activity compared with other UBXN family members. They demonstrated that, after viral infection, UBXN1 bound MAVS and disrupted the MAVS-TRAF3 (601896)/TRAF6 (602355) signaling complex, as well as downstream antiviral immune responses.MAPPING
Gross (2015) mapped the UBXN1 gene to chromosome 11q12.3 based on an alignment of the UBXN1 sequence (GenBank GENBANK BC000902) with the genomic sequence (GRCh38). ... More on the omim web site
May 13, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616378 was added.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed