CARD10 (caspase recruitment domain family, member 10)

2014-08-01   Gamze Ayaz , Mesut Muyan 

Department of Biological Sciences, Middle East Technical University, Ankara, Turkey




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.



The human CARD10 gene (NM_014550) contains 20 exons and the encoding sequence is 3099 bases.


No reported pseudogene.



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).
Atlas Image
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.


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).


CARD10 is localized in the cytoplasm (Li et al., 2012).


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).


CARD10 (CARMA3/Bimp1) shares a high degree of amino-acid sequence, structure and functional homology with CARD11 (CARMA1/Bimp2) and CARD14 (CARMA2/Bimp3).



Gene mutations have not been described yet.

Implicated in

Entity name
Breast cancer
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
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
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
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
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
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
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).


Pubmed IDLast YearTitleAuthors
229923432012microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-κB by targeting CARD10 and COPS8 in gastric cancer.Crone SG et al
246339212014CARMA3 is upregulated in human pancreatic carcinoma, and its depletion inhibits tumor proliferation, migration, and invasion.Du S et al
238933822014CARMA3 is overexpressed in human glioma and promotes cell invasion through MMP9 regulation in A172 cell line.Feng X et al
174380012007CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{kappa}B activation.Grabiner BC et al
214063992011CARMA3 is crucial for EGFR-Induced activation of NF-κB and tumor progression.Jiang T et al
226158402012Overexpression of CARMA3 in non-small-cell lung cancer is linked for tumor progression.Li Z et al
177244682008Protein 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
171019772007CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells.McAllister-Lucas LM et al
228848002012CARMA3 is overexpressed in colon cancer and regulates NF-κB activity and cyclin D1 expression.Miao Z et al
174288012007CARMA1 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
112594432001Card10 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
237718512013Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma.Wu GL et al
237089602013CARMA3 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


dbSNP: 29775
ClinVar: 29775
TCGA: ENSG00000100065


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
NF-kappa B signaling pathwayKEGGhsa04064
NF-kappa B signaling pathwayKEGGko04064

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
191121072009CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB through the CBM (Carma3/Bcl10/Malt1) complex.131
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
171019772007CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells.81
236089172013Whole-exome sequencing and imaging genetics identify functional variants for rate of change in hippocampal volume in mild cognitive impairment.43
213070882011Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area.38
186766802008Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.32
206950762009CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through the Carma3/Bcl10/Malt1 complex.31
214063992011CARMA3 is crucial for EGFR-Induced activation of NF-κB and tumor progression.31
151843902004Physical and functional interaction of CARMA1 and CARMA3 with Ikappa kinase gamma-NFkappaB essential modulator.28
202374962010New genetic associations detected in a host response study to hepatitis B vaccine.27


Gamze Ayaz ; Mesut Muyan

CARD10 (caspase recruitment domain family, member 10)

Atlas Genet Cytogenet Oncol Haematol. 2014-08-01

Online version: