CARD10 (caspase recruitment domain family, member 10)
2014-08-01 Gamze Ayaz , Mesut Muyan AffiliationDepartment of Biological Sciences, Middle East Technical University, Ankara, Turkey
Identity
HGNC
LOCATION
22q13.1
LOCUSID
ALIAS
BIMP1,CARMA3
FUSION GENES
Abstract
Caspase recruitment domain family, member 10, CARD10 (also known as CARMA3 or Bimp1), is a member of the membrane-associated guanylate kinase (MAGUK) superfamily proteins that act to organize signaling at the plasma membrane. This family of proteins contains Src-homology 3 (SH3), PDZ, GuK domains and caspase recruitment domain (CARD). The amino-terminally located CARD of CARD10 functions as an activator of BCL10 and NF-kappaB (NF-kB) signaling critical for the regulation of cellular survival and proliferation.
DNA/RNA
Description
The human CARD10 gene (NM_014550) contains 20 exons and the encoding sequence is 3099 bases.
Pseudogene
No reported pseudogene.
Proteins
Description
CARD10 (NP_055365) is a 1032 amino-acid long protein with a molecular mass of 116 kDa. This protein consists of antiparallel alpha helices. CARD10 contains an N-terminal CARD domain, followed by a central coiled-coil (CC) domain and a C-terminal region encompassing a PDZ domain, a SH3 domain and a GUK domain (Wang et al., 2001). The CARD domain has a hydrophobic core and a hydrophilic outer surface, which mediate the interaction with the CARD domain of other proteins (Hayes-Bouchier et al., 2002; Sun, 2010). Coiled-coil domain is responsible for dimerization (Tanner et al., 2007).
The structural domains of CARD10 protein are shown in different color boxes. CARD, caspase-recruitment domain; PDZ, PSD95, DLGA and ZO1 homology domain; SH3 domain, SRC-homology 3; and GUK domain, guanylate kinase. The numbers correspond to the amino-acid sequence.
Expression
CARD10 is expressed in a variety of epithelial and mesenchymal tissues including heart, kidney and liver (Wang et al., 2001; McAllister-Lucas et al., 2007). It was reported that CARD10 is over-expressed in several cancers including breast, ovarian, colon, lung and glioma cancer. It was also shown that CARD10 deficiency affects cancer cell proliferation, survival, migration and invasion (Jiang et al., 2011).
Localisation
CARD10 is localized in the cytoplasm (Li et al., 2012).
Function
CARD10 participates in the organization of membrane signaling involved in cellular proliferation and death through highly specific CARD-CARD homophilic interactions. It appears that CARD10 acting as a scaffold is involved in NF-kB activation through interactions with Bcl10 and MALT1 (Grabiner et al., 2007; McAllister-Lucas et al., 2007).
Mutations
Note
Gene mutations have not been described yet.
Implicated in
Entity name
Breast cancer
Disease
The levels of CARD10 protein are reported to be significantly higher in breast cancer than in normal breast tissue. It appears that CARD10 over-expression correlates with tumor, node and metastasis (TNM) stage, tumor size and ErbB2, also known as HER2 (from human epidermal growth factor receptor 2) or HER2/neu, over-expression. The observations that CARD10 leads to the up-regulation of cyclin D1, which is involved in proliferation, and of Bcl-2, a critical component in apoptosis, gene expressions in cell models derived from breast carcinoma (Zhao et al., 2013) is consistent with suggestion that CARD10 is involved in cell survival and proliferation.
Entity name
Glioma
Disease
CARD10 is over-expressed in glioma and correlates with tumor grades (Grade I, II, III and IV) but not with age or gender. Knocking down of CARD10 expression is shown to inhibit the proliferation and invasion of glioma cell lines (Feng et al., 2014).
Entity name
Colon cancer
Disease
CARD10 is also over-expressed in colon cancer samples compared to the normal tissue. The expression levels appear to associate with TNM and the proliferation index. Experimental studies suggest that CARD10 is a positive regulator of colon cancer proliferation (Miao et al., 2012).
Entity name
Renal cell carcinoma
Disease
CARD10 mRNA expression was found to be significantly higher in renal cell carcinoma tissues compared with noncancerous renal tissues. Furthermore, it was shown that the high level of the CARD10 gene expression is associated with tumor size, histological differentiation, tumor stage and the presence of metastasis (Wu et al., 2013).
Entity name
Ovarian cancer
Disease
CARD10 over-expression was observed to be positively correlated with tumor histology in ovarian cancer. It was shown that CARD10 depletion in various ovarian cancer cell lines inhibited cell proliferation and prevented cell cycle progression (Xie et al., 2014). It was also reported that protein kinase C alpha-CARD10 signaling axis plays an essential role in the lysophosphatidic acid (LPA)-induced in vitro invasion of ovarian cancer cells (Mahanivong et al., 2008).
Entity name
Pancreatic carcinoma
Note
CARD10 was reported to be over-expressed in human pancreatic cancer (Du et al., 2014). Moreover, CARD10 appears to regulate malignant cell growth, invasion and NF-kB signaling (Du et al., 2014).
Entity name
Non-small-cell lung cancer
Disease
As in other tissue cancers, the level of CARD10 protein is higher in non-small-cell lung cancer (NSCLC) than in normal lung tissues. There is a significant correlation between CARD10 levels and TNM stage (Li et al., 2012).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 22992343 | 2012 | microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-κB by targeting CARD10 and COPS8 in gastric cancer. | Crone SG et al |
| 24633921 | 2014 | CARMA3 is upregulated in human pancreatic carcinoma, and its depletion inhibits tumor proliferation, migration, and invasion. | Du S et al |
| 23893382 | 2014 | CARMA3 is overexpressed in human glioma and promotes cell invasion through MMP9 regulation in A172 cell line. | Feng X et al |
| 17438001 | 2007 | CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{kappa}B activation. | Grabiner BC et al |
| 21406399 | 2011 | CARMA3 is crucial for EGFR-Induced activation of NF-κB and tumor progression. | Jiang T et al |
| 22615840 | 2012 | Overexpression of CARMA3 in non-small-cell lung cancer is linked for tumor progression. | Li Z et al |
| 17724468 | 2008 | Protein kinase C alpha-CARMA3 signaling axis links Ras to NF-kappa B for lysophosphatidic acid-induced urokinase plasminogen activator expression in ovarian cancer cells. | Mahanivong C et al |
| 17101977 | 2007 | CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells. | McAllister-Lucas LM et al |
| 22884800 | 2012 | CARMA3 is overexpressed in colon cancer and regulates NF-κB activity and cyclin D1 expression. | Miao Z et al |
| 17428801 | 2007 | CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation. | Tanner MJ et al |
| 11259443 | 2001 | Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B. | Wang L et al |
| 23771851 | 2013 | Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma. | Wu GL et al |
| 23708960 | 2013 | CARMA3 overexpression accelerates cell proliferation and inhibits paclitaxel-induced apoptosis through NF-κB regulation in breast cancer cells. | Zhao T et al |
Other Information
Locus ID:
NCBI: 29775
MIM: 607209
HGNC: 16422
Ensembl: ENSG00000100065
Variants:
dbSNP: 29775
ClinVar: 29775
TCGA: ENSG00000100065
COSMIC: CARD10
RNA/Proteins
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| NF-kappa B signaling pathway | KEGG | hsa04064 |
| NF-kappa B signaling pathway | KEGG | ko04064 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36618379 | 2022 | CARMA3: A potential therapeutic target in non-cancer diseases. | 2 |
| 36618379 | 2022 | CARMA3: A potential therapeutic target in non-cancer diseases. | 2 |
| 34190011 | 2021 | CARMA3 Transcriptional Regulation of STMN1 by NF-κB Promotes Renal Cell Carcinoma Proliferation and Invasion. | 5 |
| 34190011 | 2021 | CARMA3 Transcriptional Regulation of STMN1 by NF-κB Promotes Renal Cell Carcinoma Proliferation and Invasion. | 5 |
| 30723269 | 2020 | The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer. | 16 |
| 31939627 | 2020 | CARD10 promotes the progression of renal cell carcinoma by regulating the NF‑κB signaling pathway. | 7 |
| 32238915 | 2020 | Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity. | 2 |
| 30723269 | 2020 | The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer. | 16 |
| 31939627 | 2020 | CARD10 promotes the progression of renal cell carcinoma by regulating the NF‑κB signaling pathway. | 7 |
| 32238915 | 2020 | Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity. | 2 |
| 31565867 | 2019 | Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells. | 8 |
| 31576094 | 2019 | CARMA3/NF-κB signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate. | 8 |
| 31565867 | 2019 | Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells. | 8 |
| 31576094 | 2019 | CARMA3/NF-κB signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate. | 8 |
| 29259013 | 2018 | The CARMA3-Bcl10-MALT1 Signalosome Drives NFκB Activation and Promotes Aggressiveness in Angiotensin II Receptor-Positive Breast Cancer. | 51 |
Citation
Gamze Ayaz ; Mesut Muyan
CARD10 (caspase recruitment domain family, member 10)
Atlas Genet Cytogenet Oncol Haematol. 2014-08-01
Online version: http://atlasgeneticsoncology.org/gene/43187/new-content/
