CARD10 (caspase recruitment domain family, member 10)

2014-08-01 Gamze Ayaz , Mesut Muyan Affiliation

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

Identity

HGNC

CARD10

LOCATION

22q13.1

LOCUSID

29775

ALIAS

BIMP1,CARMA3

FUSION GENES

Show Gene Fusions

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).

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 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

Gene ID	Transcript ID	Uniprot
ENSG00000100065	ENST00000251973	Q9BWT7
ENSG00000100065	ENST00000403299	Q9BWT7
ENSG00000100065	ENST00000406271	Q9BWT7
ENSG00000100065	ENST00000433485	B0QYC3
ENSG00000100065	ENST00000437756	B0QYC4

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
NF-kappa B signaling pathway	KEGG	hsa04064
NF-kappa B signaling pathway	KEGG	ko04064

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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/card10-(caspase-recruitment-domain-family-member-10)