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| Description | 348 amino acids; 38.518 kDa. CapG protein contains three gelsolin-like repeats in the position 27-75 (49), 148-188 (41), and 261-307 (47); and a nuclear localization signal (NES) 137-146 (10). Three natural variants, VAR-047776 (V41I), VAR-047777 (R198W), and VAR-047778 (R335H) have been reported.
Isoforms: Altogether 15 different isoforms (eight complete, one COOH complete, and six partial) have been predicted. Isoform jApr07 is annotated, contains 79 amino acids N-terminal to the first AUG. |
| Expression | Ubiquitously expressed; highly expressed in prostate, lung, and kidney. |
| Localisation | Cytoplasmic (52.2 %), cytoskeletal (21.7 %), and nuclear (13.0 %), according to PSORT II prediction. |
| Function | CAPG encodes a member of the gelsolin/villin family of actin-regulatory proteins that reversibly blocks (capping) the barbed ends of F-actin filaments in a Ca 2+and phosphoinositide-regulated manner, but does not sever preformed actin filaments. Capping contributes to the control of actin-based motility in non-muscle cells. Dysregulation of actin-based motility is a prominent factor in cell transformation and is probably associated with carcinogenesis. CAPG is also involved in cell signaling, receptor-mediated membrane ruffling, and phagocytosis. |
| Homology | The percent identity below represents identity of CAPG over an aligned region in UniGene.
- Pan troglodytes: 99.7 % (percentage identity)
- Macaca mulatta: 99.7 %
- Mus musculus: 95.4 %
- Rattus norvegicus: 92.8 %
- Bos taurus: 91.1 %
- Danio rerio: 61.7 % |
| Entity | Breast cancer |
| Disease | CAPG is expressed at higher levels in metastasizing breast cancer, than in normal breast epithelium. Furthermore, CapG protein is also transported more rapidly into the nucleus of the breast cancerous cells than the corresponding benign cells. CapG knockdown reduces invasiveness in Matrigel invasion assay, which supports the role of CAPG in cell motility. Thus, increased expression of CAPG leads to dysregulation of cell motility that promotes tumor invasion. |
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| Entity | Oral carcinogenesis |
| Note | Significant overexpression of CapG protein was detected in oral squamous-cell carcinoma cells (OSCCs) and oral premalignant lesions (OPLs). Enhanced expression of CapG was also associated with large tumour size and advanced staging of OSCCs. Therefore, CapG may initiate or activate the neoplastic process of OSCC cells including the regulation of biologic behaviour of aggressive forms of cells rather than as a suppressor. |
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| Entity | Ovarian carcinomas |
| Disease | In a Swedish women population, CAPG was expressed more in tumors among deceased patients than survivors with ovarian carcinomas. The stage III serous papillary adenocarcinomas of the ovary show higher CAPG expression and this is possibly correlated with the advance disease stage. Overexpression of CAPG promotes aggressive tumor progression. |
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| Entity | Pancreatic cancer |
| Note | Up regulation and multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. High level of CapG protein may possibly play an important role in pancreatic cancer cell motility and consequently dissemination. |
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| Entity | Ocular melanoma |
| Note | CapG, which is a unique regulator of the actin cytoskeleton, is expressed in malignant melanomas of the uvea but not to a significant extent in normal uveal melanocytes. |
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| Entity | Tumorigenic progression in cell lines |
| Note | Expression of the CapG protein was lost in the tumorigenic cell line, isolated from a human diploid fibroblast lineage. The CapG protein expression was lost also in cancer cell lines including stomach cancer, lung cancer and melanoma. The human stomach cancer cell line AZ 521 became non-tumorigenic after the introduction of CapG cDNA. Moreover, CapG expression was repressed in small-cell lung cancer tissues. These results indicate that CapG is a tumor suppressor gene involved in the tumorigenic progression of certain cancers. |
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| Molecular cloning of human macrophage capping protein cDNA. A unique member of the gelsolin/villin family expressed primarily in macrophages. |
| Dabiri GA, Young CL, Rosenbloom J, Southwick FS. |
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| PMID 1322908 |
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| PMID 18059028 |
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