Alternative titles; symbolsKIAA0794HGNC Approved Gene Symbol: UBXN7Cytogenetic location: 3q29 Genomic coordinates (GRCh38): 3:196,347,658-196,454,322 (from N...
Alternative titles; symbols
HGNC Approved Gene Symbol: UBXN7
Cytogenetic location: 3q29 Genomic coordinates (GRCh38): 3:196,347,658-196,454,322 (from NCBI)
Members of the UBA-UBX family, such as UBXN7, contain both a UBA domain, which interacts with ubiquitinated proteins, and a UBX domain, which interacts with the p97 ATPase (VCP; 601023). Independently of its role as a ubiquitin-binding adaptor for p97, UBXN7 interacts with neddylated cullins and causes accumulation of the CUL2 (603135) substrate HIF1A (603348) (Bandau et al., 2012).
▼ Cloning and Expression
By searching for cDNAs encoding large proteins expressed in brain, Nagase et al. (1998) identified a cDNA encoding UBXN7, which they called KIAA0794. The predicted protein contains 490 amino acids. RT-PCR analysis detected expression of UBXN7 in all 10 human tissues examined, with highest expression in ovary, followed by brain, lung, and kidney. Weakest expression was in spleen.
Bandau et al. (2012) reported that the 489-amino acid human UBXN7 protein contains an N-terminal UBA domain, followed by a UAS domain, a ubiquitin interaction motif (UIM), and a C-terminal UBX domain.
▼ Gene Function
By immunoprecipitation analysis, Bandau et al. (2012) showed that ubiquitylation was not necessary for interaction of UBXN7 with CUL2, which allowed accumulation of HIF1A. UBXN7 preferentially interacted with CUL2 that had been neddylated at lys689 and lys719. Mutation analysis indicated that the central UIM of UBXN7 was necessary for interaction with CUL2 following NEDD8 (603171) modification; the UBA, UAS, and UBX domains of UBXN7 were not required for this interaction. Overexpression of UBXN7 resulted in HIF1A accumulation in a UIM-dependent manner. Bandau et al. (2012) proposed that sequestration of CUL2 in its neddylated form by UBXN7 negatively regulates the ubiquitin ligase activity of the CRL2 complex, which consists of CUL2, RBX1 (603814), elongin B (ELOB; 600787), and elongin C (ELOC; 600788). They suggested that sequestration of CUL2 by UBXN7 may also prevent recruitment of ubiquitin receptors other than p97 to nuclear HIF1A.
Gross (2015) mapped the UBXN7 gene to chromosome 3q29 based on an alignment of the UBXN7 sequence (GenBank BC160090) with the genomic sequence (GRCh38).