CARD10 (caspase recruitment domain family, member 10)

2014-08-01   Gamze Ayaz  , Mesut Muyan  

Department 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).
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.

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).

Homology

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

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 IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 29775
MIM: 607209
HGNC: 16422
Ensembl: ENSG00000100065

Variants:

dbSNP: 29775
ClinVar: 29775
TCGA: ENSG00000100065
COSMIC: CARD10

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000100065ENST00000251973Q9BWT7
ENSG00000100065ENST00000403299Q9BWT7
ENSG00000100065ENST00000406271Q9BWT7
ENSG00000100065ENST00000433485B0QYC3
ENSG00000100065ENST00000437756B0QYC4

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45

Pathways

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

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
366183792022CARMA3: A potential therapeutic target in non-cancer diseases.2
366183792022CARMA3: A potential therapeutic target in non-cancer diseases.2
341900112021CARMA3 Transcriptional Regulation of STMN1 by NF-κB Promotes Renal Cell Carcinoma Proliferation and Invasion.5
341900112021CARMA3 Transcriptional Regulation of STMN1 by NF-κB Promotes Renal Cell Carcinoma Proliferation and Invasion.5
307232692020The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer.16
319396272020CARD10 promotes the progression of renal cell carcinoma by regulating the NF‑κB signaling pathway.7
322389152020Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity.2
307232692020The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer.16
319396272020CARD10 promotes the progression of renal cell carcinoma by regulating the NF‑κB signaling pathway.7
322389152020Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity.2
315658672019Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells.8
315760942019CARMA3/NF-κB signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate.8
315658672019Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells.8
315760942019CARMA3/NF-κB signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate.8
292590132018The 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/tumors-explorer/css/case-report-explorer/