Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins. (updated: Oct. 25, 2017)
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.
No sequence conservation computed yet.
Total structural coverage: 0%
No model available.
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The reference OMIM entry for this protein is 611649
Chromosome 10 open reading frame 97; c10orf97
Card-containing protein; carp
DESCRIPTION
C10ORF97 is a member of the caspase-associated recruitment domain (CARD) family of proteins that play a role in apoptosis (Liu et al., 2002).
CLONING
By large-scale sequencing of a human aorta cDNA library, Liu et al. (2002) cloned C10ORF97, which they called CARP. The deduced 445-amino acid protein has a calculated molecular mass of 49.7 kD and contains a nuclear receptor-binding motif, a caspase-associated recruitment domain, 2 EF-hand calcium-binding motifs, and an estimated 42% alpha-helix content. C10ORF97 also contains 17 potential phosphorylation sites and 4 N-myristoylation sites. C10ORF97 shares 95.5% amino acid similarity with its mouse ortholog and shares similarity over the CARD domain with many apoptosis proteins including APAF1 (
602233), RAIDD (CRADD;
603454), and CASP1 (
147678). Northern blot analysis of human tissues detected strong expression in heart, skeletal muscle, and kidney, with weak expression in liver and brain. Tumor cell lines analyzed showed ubiquitous expression with highest levels in Helas S3 and lung carcinoma A549 cells. Immunostaining and subcellular fractionation studies localized C10ORF97 to the nucleus when expressed in HEK293S cells.
GENE FUNCTION
Using fluorescence microscopy and DNA staining, Liu et al. (2002) showed that overexpression of C10ORF97 induced apoptosis in HEK293 and lung carcinoma A549 cells. Overexpression of C10ORF97 significantly inhibited cell proliferation in several tumor cell lines. Antisense inhibition of cells overexpressing C10ORF97 stimulated proliferation and abolished the effect of C10ORF97 on apoptosis. Shi et al. (2011) found downregulation of C10ORF97 in nonsmall cell lung cancer (NSCLC; see
211980) tissue. Low C10ORF97 staining was found in 51.7% (217 of 420) of NSCLC samples and in 9% (19 of 210) of normal lung samples. By contrast, only 5.2% (22 of 420) of the NSCLC samples and 40.5% (85 of 210) of the normal lung samples showed high C10ORF97 staining. Overexpression of C10ORF97 in lung cancer A549 cells suppressed cell proliferation compared to controls, and silencing with siRNA promoted A549 cell proliferation. Overexpression of C10ORF97 in A549 cells reduced colony-forming ability, inhibited cell adhesion, and caused decreased cellular motility in vitro. These findings were replicated in mice in vivo who were injected with tumor cells: mice treated with an adenoviral vector carrying the C10ORF97 gene showed a significant suppression of tumor growth compared to untreated mice. Analysis of cell cycle kinetics using flow cytometry showed that C10ORF97 overexpression caused arrest of A549 cells in G1 phase, with a decrease in the number of cells in S phase. C10ORF97 modulated the expression of several cell cycle regulators, including an increase of p27 (CDKN1B;
600778), and was shown to interact and interfere with JAB1 (COPS5;
604850) function. Through this interaction, C10ORF97 inhibited JAB1-mediated activation of AP1 (see JUN oncogene,
165160) in a dose-dependent manner, and blocked the JAB1-mediated translation of p27 from the nucleus to the cytoplasm. The findings were consistent with C10ORF97 acting as a tumor suppressor gene with a role in regulation of the cell cycle.
GENE STRUCTURE
Liu et al. (2002) determined that the C10ORF97 gene contains 15 exons.
MAPPING
By genomic sequence analysis, Liu et al. (2002) mapped the C10ORF97 gene to chromosome 10p13.
MOLECULAR GENETICS
For discus ...
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Subscribe to this protein entry history
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 611649 was added.