HGNC Approved Gene Symbol: CHERPCytogenetic location: 19p13.11 Genomic coordinates (GRCh38): 19:16,517,893-16,542,436 (from NCBI)▼ DescriptionCHERP is a nucl...
HGNC Approved Gene Symbol: CHERP
Cytogenetic location: 19p13.11 Genomic coordinates (GRCh38): 19:16,517,893-16,542,436 (from NCBI)
CHERP is a nuclear protein involved in the regulation of alternative splicing of pre-mRNA (Lin-Moshier et al., 2013; Sasaki-Osugi et al., 2013).
▼ Cloning and Expression
Laplante et al. (2000) cloned CHERP from a human erythroleukemia (HEL) cell expression library. The deduced 884-amino acid protein has a calculated molecular mass of 100 kD. It contains 2 transmembrane domains, a polyglutamine tract, a serine/arginine (SR)-rich domain, several putative phosphorylation sites, and a C-terminal endoplasmic reticulum (ER) retention motif. Northern blot analysis detected a 4.2-kb CHERP transcript in human brain, placenta, lung, liver, kidney, pancreas, and cardiac and skeletal muscle, as well as in cultured megakaryoblastic HEL and Dami cells. A 6.4-kb transcript was also detected in cardiac and skeletal muscle. Immunolocalization showed distribution of CHERP throughout the cytoplasmic region in HEL cells.
By bioinformatic analysis, Lin-Moshier et al. (2013) determined that human CHERP contains an N-terminal SURP/SWAP domain, followed by an RNA polymerase II (POLR2A; 180660) C-terminal domain (CTD)-interacting domain (CID), an SR-rich domain, and a C-terminal G-patch motif. The authors found no evidence for transmembrane domains in CHERP. Immunofluorescence and live-cell imaging showed that human CHERP localized to nuclear speckles.
▼ Gene Function
Laplante et al. (2000) found that knockdown of CHERP inhibited intracellular Ca(2+) mobilization and decreased proliferation of HEL cells.
By truncation analysis, Lin-Moshier et al. (2013) demonstrated that the C-terminal region of CHERP was necessary and sufficient to direct nuclear targeting of CHERP. Immunoprecipitation and mass spectrometric analyses revealed that CHERP interacted with nuclear proteins, including SR140 (U2SURP; 617849). Knockdown of CHERP caused a decrease in SR140 expression levels in HEK293 cells.
By immunoprecipitation and live-cell imaging analysis, Sasaki-Osugi et al. (2013) found that ALG2 (607905) interacted with CHERP and transiently accumulated at nuclear speckles in a Ca(2+)-dependent manner. Western blot analysis showed that the SR-rich region of CHERP was constitutively phosphorylated at its ser residues. Deletion analysis revealed that a proline-rich region (PRR) of CHERP contained multiple ALG2-binding sites and was involved in interaction with phosphorylated RNA polymerase II. RNA immunoprecipitation assays demonstrated that CHERP physically associated with IP3R1 (ITPR1; 147265) RNA, and knockdown of CHERP or ALG2 altered the splicing pattern of IP3R1 pre-mRNA in HT1080 cells.
Laplante et al. (2000) reported that the CHERP gene maps to chromosome 19p13.1.