UBIQUITIN-SPECIFIC PROTEASE 19; USP19

Alternative titles; symbols

• KIAA0891

HGNC Approved Gene Symbol: USP19

Cytogenetic location: 3p21.31 Genomic coordinates (GRCh38): 3:49,108,049-49,120,932 (from NCBI)

▼ Description
USP19 is a ubiquitin protein ligase (EC 3.4.19.12) with a role in regulating cell cycle progression (Lu et al., 2009).

▼ Cloning and Expression
By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (1998) cloned USP19, which they designated KIAA0891. The deduced 1,371-amino acid protein shares significant similarity with the ubiquitin protease UNPH (USP4; 603486). RT-PCR ELISA detected highest expression in fetal liver, followed by adult spinal cord. All other tissues, including adult and fetal brain, showed much lower expression, and no expression was detected in spleen.

▼ Gene Function
p27(KIP1) (CDKN1B; 600778) is a cyclin-dependent kinase inhibitor that regulates the G1/S transition. Using rat myoblast and fibroblast cell lines, Lu et al. (2009) showed that Usp19 regulated p27(KIP1) levels by deubiquitinating and stabilizing Kpc1 (RNF123; 614472), an E3 ubiquitin ligase that ubiquitinates cytosolic p27(KIP1) and targets it for proteasomal degradation at G1 phase. Immunoprecipitation analysis revealed that Usp19 interacted directly with Kpc1. Knockdown of Usp19 resulted in loss of Kpc1, accumulation of p27(KIP1), inhibition of cell proliferation, and slower progression from G0/G1 to S phase.

▼ Mapping
By radiation hybrid analysis, Nagase et al. (1998) mapped the USP19 gene to chromosome 3.

Hartz (2011) mapped the USP19 gene to chromosome 3p21.31 based on an alignment of the USP19 sequence (GenBank AB020698) with the genomic sequence (GRCh37).