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CARD10 (caspase recruitment domain family, member 10)

Written2014-08Gamze Ayaz, Mesut Muyan
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey

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.
CARD10 (CARMA3) is reported to be over-expressed in various cancer types that include breast, glioma, colon and non-small-cell lung cancers. It appears that the over-expression of CARD10 correlates with tumor status positioning CARD10 as a novel therapeutic target for the treatment of various cancers.

Keywords CARD10 (CARMA3), NF-kB signaling, Apoptosis, Bcl-10, MALT1.

(Note : for Links provided by Atlas : click)

Identity

Alias_namescaspase recruitment domain family
Alias_symbol (synonym)CARMA3
BIMP1
Other alias
HGNC (Hugo) CARD10
LocusID (NCBI) 29775
Atlas_Id 43187
Location 22q13.1  [Link to chromosome band 22q13]
Location_base_pair Starts at 37490362 and ends at 37519203 bp from pter ( according to hg19-Feb_2009)  [Mapping CARD10.png]
Fusion genes
(updated 2016)
CARD10 (22q13.1) / CAMK2N1 (1p36.12)RBM34 (1q42.3) / CARD10 (22q13.1)

DNA/RNA

Description The human CARD10 gene (NM_014550) contains 20 exons and the encoding sequence is 3099 bases.
Pseudogene No reported pseudogene.

Protein

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

Note
  
Entity 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 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 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 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 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 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 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).
  

To be noted

miRNA: It was reported that microRNA-146a which is a modulator of inflammatory signals, directly targets CARD10 and COPS8 (COP9 signalosome complex subunit 8) inhibiting the G-protein coupled receptor (GPRC)-mediated activation of NF-kB. It was also found that miR-146a represses the secretion of chemokines and growth factors controlled by NF-kB. It was therefore suggested that miR-146a may act as a tumor suppressor by inhibiting NF-kB activity (Crone et al., 2012).

Bibliography

microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-kB by targeting CARD10 and COPS8 in gastric cancer.
Crone SG, Jacobsen A, Federspiel B, Bardram L, Krogh A, Lund AH, Friis-Hansen L.
Mol Cancer. 2012 Sep 20;11:71. doi: 10.1186/1476-4598-11-71.
PMID 22992343
 
CARMA3 is upregulated in human pancreatic carcinoma, and its depletion inhibits tumor proliferation, migration, and invasion.
Du S, Jia L, Zhang Y, Fang L, Zhang X, Fan Y.
Tumour Biol. 2014 Jun;35(6):5965-70. doi: 10.1007/s13277-014-1791-6. Epub 2014 Mar 16.
PMID 24633921
 
CARMA3 is overexpressed in human glioma and promotes cell invasion through MMP9 regulation in A172 cell line.
Feng X, Miao G, Han Y, Xu Y.
Tumour Biol. 2014 Jan;35(1):149-54. doi: 10.1007/s13277-013-1018-2. Epub 2013 Jul 27.
PMID 23893382
 
CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{kappa}B activation.
Grabiner BC, Blonska M, Lin PC, You Y, Wang D, Sun J, Darnay BG, Dong C, Lin X.
Genes Dev. 2007 Apr 15;21(8):984-96.
PMID 17438001
 
CARMA3 is crucial for EGFR-Induced activation of NF-kB and tumor progression.
Jiang T, Grabiner B, Zhu Y, Jiang C, Li H, You Y, Lang J, Hung MC, Lin X.
Cancer Res. 2011 Mar 15;71(6):2183-92. doi: 10.1158/0008-5472.CAN-10-3626.
PMID 21406399
 
Overexpression of CARMA3 in non-small-cell lung cancer is linked for tumor progression.
Li Z, Qu L, Dong Q, Huang B, Li H, Tang Z, Xu Y, Luo W, Liu L, Qiu X, Wang E.
PLoS One. 2012;7(5):e36903. doi: 10.1371/journal.pone.0036903. Epub 2012 May 15.
PMID 22615840
 
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, Chen HM, Yee SW, Pan ZK, Dong Z, Huang S.
Oncogene. 2008 Feb 21;27(9):1273-80. Epub 2007 Aug 27.
PMID 17724468
 
CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells.
McAllister-Lucas LM, Ruland J, Siu K, Jin X, Gu S, Kim DS, Kuffa P, Kohrt D, Mak TW, Nunez G, Lucas PC.
Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):139-44. Epub 2006 Nov 13.
PMID 17101977
 
CARMA3 is overexpressed in colon cancer and regulates NF-kB activity and cyclin D1 expression.
Miao Z, Zhao T, Wang Z, Xu Y, Song Y, Wu J, Xu H.
Biochem Biophys Res Commun. 2012 Sep 7;425(4):781-7. doi: 10.1016/j.bbrc.2012.07.152. Epub 2012 Aug 2.
PMID 22884800
 
GPCR-CARMA3- NF-kappaB signaling axis: A novel drug target for cancer therapy.
Sun JY.
Clinical Oncology and Cancer Research. 2010 June;7(3):159-168.
 
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, Hanel W, Gaffen SL, Lin X.
J Biol Chem. 2007 Jun 8;282(23):17141-7. Epub 2007 Apr 11.
PMID 17428801
 
Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B.
Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S, Glucksmann MA, DiStefano PS, Alnemri ES, Bertin J.
J Biol Chem. 2001 Jun 15;276(24):21405-9. Epub 2001 Mar 20.
PMID 11259443
 
Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma.
Wu GL, Yuan JL, Huang XD, Rong JF, Zhang LX, Liu YP, Wang FL.
Tumour Biol. 2013 Dec;34(6):3431-5. doi: 10.1007/s13277-013-0917-6. Epub 2013 Jun 15.
PMID 23771851
 
CARMA3 overexpression accelerates cell proliferation and inhibits paclitaxel-induced apoptosis through NF-kB regulation in breast cancer cells.
Zhao T, Miao Z, Wang Z, Xu Y, Wu J, Liu X, You Y, Li J.
Tumour Biol. 2013 Oct;34(5):3041-7. doi: 10.1007/s13277-013-0869-x. Epub 2013 May 25.
PMID 23708960
 

Citation

This paper should be referenced as such :
Ayaz G, Muyan M
CARD10 (caspase recruitment domain family, member 10);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/CARD10ID43187ch22q13.html


External links

Nomenclature
HGNC (Hugo)CARD10   16422
Cards
AtlasCARD10ID43187ch22q13
Entrez_Gene (NCBI)CARD10  29775  caspase recruitment domain family member 10
AliasesBIMP1; CARMA3
GeneCards (Weizmann)CARD10
Ensembl hg19 (Hinxton)ENSG00000100065 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000100065 [Gene_View]  chr22:37490362-37519203 [Contig_View]  CARD10 [Vega]
ICGC DataPortalENSG00000100065
TCGA cBioPortalCARD10
AceView (NCBI)CARD10
Genatlas (Paris)CARD10
WikiGenes29775
SOURCE (Princeton)CARD10
Genetics Home Reference (NIH)CARD10
Genomic and cartography
GoldenPath hg38 (UCSC)CARD10  -     chr22:37490362-37519203 -  22q13.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CARD10  -     22q13.1   [Description]    (hg19-Feb_2009)
EnsemblCARD10 - 22q13.1 [CytoView hg19]  CARD10 - 22q13.1 [CytoView hg38]
Mapping of homologs : NCBICARD10 [Mapview hg19]  CARD10 [Mapview hg38]
OMIM607209   
Gene and transcription
Genbank (Entrez)AF086324 AK057334 AK074906 AK296176 AY028896
RefSeq transcript (Entrez)NM_014550
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CARD10
Cluster EST : UnigeneHs.57973 [ NCBI ]
CGAP (NCI)Hs.57973
Alternative Splicing GalleryENSG00000100065
Gene ExpressionCARD10 [ NCBI-GEO ]   CARD10 [ EBI - ARRAY_EXPRESS ]   CARD10 [ SEEK ]   CARD10 [ MEM ]
Gene Expression Viewer (FireBrowse)CARD10 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)29775
GTEX Portal (Tissue expression)CARD10
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9BWT7   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9BWT7  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9BWT7
Splice isoforms : SwissVarQ9BWT7
PhosPhoSitePlusQ9BWT7
Domaine pattern : Prosite (Expaxy)CARD (PS50209)   
Domains : Interpro (EBI)CARD    DEATH-like_dom    P-loop_NTPase   
Domain families : Pfam (Sanger)CARD (PF00619)   
Domain families : Pfam (NCBI)pfam00619   
Conserved Domain (NCBI)CARD10
DMDM Disease mutations29775
Blocks (Seattle)CARD10
SuperfamilyQ9BWT7
Human Protein AtlasENSG00000100065
Peptide AtlasQ9BWT7
HPRD06233
IPIIPI00002313   IPI00848169   IPI00879696   IPI00877861   
Protein Interaction databases
DIP (DOE-UCLA)Q9BWT7
IntAct (EBI)Q9BWT7
FunCoupENSG00000100065
BioGRIDCARD10
STRING (EMBL)CARD10
ZODIACCARD10
Ontologies - Pathways
QuickGOQ9BWT7
Ontology : AmiGOprotein binding  cytoplasm  protein complex assembly  activation of NF-kappaB-inducing kinase activity  activation of NF-kappaB-inducing kinase activity  receptor signaling complex scaffold activity  CBM complex  regulation of apoptotic process  
Ontology : EGO-EBIprotein binding  cytoplasm  protein complex assembly  activation of NF-kappaB-inducing kinase activity  activation of NF-kappaB-inducing kinase activity  receptor signaling complex scaffold activity  CBM complex  regulation of apoptotic process  
NDEx NetworkCARD10
Atlas of Cancer Signalling NetworkCARD10
Wikipedia pathwaysCARD10
Orthology - Evolution
OrthoDB29775
GeneTree (enSembl)ENSG00000100065
Phylogenetic Trees/Animal Genes : TreeFamCARD10
HOVERGENQ9BWT7
HOGENOMQ9BWT7
Homologs : HomoloGeneCARD10
Homology/Alignments : Family Browser (UCSC)CARD10
Gene fusions - Rearrangements
Fusion : MitelmanRBM34/CARD10 [1q42.3/22q13.1]  [t(1;22)(q42;q13)]  
Fusion: TCGARBM34 1q42.3 CARD10 22q13.1 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCARD10 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CARD10
dbVarCARD10
ClinVarCARD10
1000_GenomesCARD10 
Exome Variant ServerCARD10
ExAC (Exome Aggregation Consortium)CARD10 (select the gene name)
Genetic variants : HAPMAP29775
Genomic Variants (DGV)CARD10 [DGVbeta]
DECIPHERCARD10 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCARD10 
Mutations
ICGC Data PortalCARD10 
TCGA Data PortalCARD10 
Broad Tumor PortalCARD10
OASIS PortalCARD10 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCARD10  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCARD10
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CARD10
DgiDB (Drug Gene Interaction Database)CARD10
DoCM (Curated mutations)CARD10 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CARD10 (select a term)
intoGenCARD10
NCG5 (London)CARD10
Cancer3DCARD10(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM607209   
Orphanet
MedgenCARD10
Genetic Testing Registry CARD10
NextProtQ9BWT7 [Medical]
TSGene29775
GENETestsCARD10
Target ValidationCARD10
Huge Navigator CARD10 [HugePedia]
snp3D : Map Gene to Disease29775
BioCentury BCIQCARD10
ClinGenCARD10
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD29775
Chemical/Pharm GKB GenePA134927444
Clinical trialCARD10
Miscellaneous
canSAR (ICR)CARD10 (select the gene name)
Probes
Litterature
PubMed46 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCARD10
EVEXCARD10
GoPubMedCARD10
iHOPCARD10
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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