Alternative titles; symbols
HGNC Approved Gene Symbol: UBAC1
Cytogenetic location: 9q34.3 Genomic coordinates (GRCh38): 9:135,932,969-135,961,373 (from NCBI)
By differential display analysis of untreated and EPO (133170)-treated primary human microvascular endothelial cells (HMVECs), followed by HMVEC cDNA library screening, Li et al. (2000) cloned GBDR1. The deduced 404-amino acid protein has a calculated molecular mass of about 44.4 kD. GBDR1 contains a C-terminal helix-loop-helix motif and an SRC (190090) homology-3 (SH3) domain. It has several putative phosphorylation sites, including 8 CK2 (see 115440) sites, as well as 1 N-glycosylation site and 2 N-myristoylation sites. The 5-prime untranslated region of the transcript contains a CpG island, and the 3-prime region contains 2 mRNA instability motifs. Northern blot analysis detected a 1.9-kb transcript expressed in both resting and EPO-stimulated HMVECs and human umbilical vein endothelial cells (HUVECs). Northern blot analysis of a multiple-tissue panel detected ubiquitous GBDR1 expression, with highest levels in heart and skeletal muscle and lowest level in lung. Western blot analysis of HMVEC lysates detected GBDR1 at an apparent molecular mass of about 46 kD. Cell fractionation revealed GBDR1 in the membrane fraction, and detergent treatment indicated that GBDR1 associates with nuclear membranes. In HMVECs, GBDR1 showed a punctate cytoplasmic distribution and a variable number of nuclear speckles.
By searching an EST database for sequences similar to rabbit Kpc2, followed by PCR of a human liver cDNA library, Kamura et al. (2004) cloned UBAC1, which they called KPC2. The deduced protein contains an N-terminal ubiquitin-like (UBL) domain and 2 C-terminal ubiquitin-associated (UBA) domains.
Although differential screening indicated that GBDR1 was upregulated following EPO treatment of HMVECs, Li et al. (2000) were unable to confirm upregulation by Northern blot analysis. However, EPO treatment increased the amount of GBDR1 in the nuclear compartment of immunostained HMVECs. In vitro phosphorylation assays determined that GBDR1 is a substrate for CK2, and Li et al. (2000) noted that 2 CK2 phosphorylation sites are near a putative nuclear localization signal.
Kamura et al. (2004) found that KPC2 interacted with the proteasome through its UBL domain and with polyubiquitinated proteins through its UBA domains. By immunoprecipitation analysis, they showed that epitope-tagged KPC2 interacted directly with KPC1 (RNF123; 614472) and that the complex exhibited pronounced E3 ubiquitin ligase activity toward p27(KIP1) (CDKN1B; 600778), but not other substrates, in the presence of E1 (UBA1; 314370), and E2 (UBCH5A, or UBE2D1; 602961) enzymes. Both mono- and polyubiquitinated forms of p27(KIP1) were detected, and polyubiquitination required either UBC4 (UBE2D2; 602962) or UBCH5A. The E3 activity of KPC1 toward p27(KIP1) was greater in the absence of PKC2. Overexpression and knockdown studies with mouse fibroblasts revealed that the KPC complex functioned in the cytoplasm, ubiquitinated p27(KIP1) during G1 phase of the cell cycle, and required nuclear export of p27(KIP1) by Crm1 (XPO1; 602559).
By somatic cell hybrid analysis and Southern blot analysis, Li et al. (2000) mapped the single-copy UBAC1 gene to chromosome 9.
Hartz (2011) mapped the UBAC1 gene to chromosome 9q34.3 based on an alignment of the UBAC1 sequence (GenBank AF068195) with the genomic sequence (GRCh37).
Hartz, P. A. Personal Communication. Baltimore, Md. 10/24/2011.
Kamura, T., Hara, T., Matsumoto, M., Ishida, N., Okumura, F., Hatakeyama, S., Yoshida, M., Nakayama, K., Nakayama, K. I. Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27(Kip1) at G1 phase. Nature Cell Biol. 6: 1229-1235, 2004. [PubMed: 15531880] [Full Text: https://doi.org/10.1038/ncb1194]
Li, C., Rodriguez, M., Adamson, J. W., Banerjee, D. Identification of a glialblastoma cell differentiation factor-related gene mRNA in human microvascular endothelial cells. Genomics 65: 243-252, 2000. [PubMed: 10857748] [Full Text: https://doi.org/10.1006/geno.2000.6176]