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CARD8 (caspase recruitment domain family, member 8)

Written2007-05Frank A. Kruyt
Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands

(Note : for Links provided by Atlas : click)


Alias_namescaspase recruitment domain family
Alias_symbol (synonym)TUCAN
Other aliasDACAR
LocusID (NCBI) 22900
Atlas_Id 913
Location 19q13.33  [Link to chromosome band 19q13]
Location_base_pair Starts at 48208086 and ends at 48241063 bp from pter ( according to hg19-Feb_2009)  [Mapping CARD8.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CARD8 (19q13.33) / BCKDHA (19q13.2)CARD8 (19q13.33) / CARD8 (19q13.33)CARD8 (19q13.33) / DDX19B (16q22.1)
CARD8 (19q13.33) / EXD3 (9q34.3)CARD8 (19q13.33) / RPA1 (17p13.3)CARD8 (19q13.33) / SULT2B1 (19q13.33)


Description The CARD8 gene contains 13 exons spanning over approximately 30 kb of genomic DNA
Transcription At least 5 transcripts have been identified generated by alternative splicing that together with different start codon usage yield different CARD8 isoforms. Gene products encoded by exons 1 to 13 and 5 to 13 yield TUCAN/CARD8-54-kDa and TUCAN/CARD8-48-kDa, respectively.


  Schematic representation of two CARD8 variants. The CARD domain, the NAC/DEFCAP/CARD7 homology domain, and the amino-terminal residues that differ between the isoforms are indicated.
Description The CARD8 gene encodes different CARD8 isoforms that contain the caspase-associated recruitment domain (CARD) in their carboxy-termini that acts as a protein-protein interaction interface. A 431 amino acids CARD8 protein of 48-kDa (TUCAN-48) has been best studied and more recently a 54-kDa isoform (TUCAN-54, 487 amino acids) was identified sharing the same CARD motif but with a different stretch of 80 amino-terminal residues. In the amino terminal part of the protein a NAC/DEFCAP/CARD7 homology domain is present.
Expression Normal tissue: wide and differential expression at mRNA level in tissues; present in heart, brain, lung, muscle, spleen, ovary; high in kidney, testis and spinal cord; absent in liver.
Cancer: the CARD8 (48 kDa) protein is differentially expressed in cancer. High levels of CARD8 expression were found in tumor cell lines, including breast, prostate, ovarian and colon cancer cells as well as high expression in non-small cell lung cancer (NSCLC) cells and with hardly detectable expression in normal lung, in contrast to a lack of expression in small-cell lung cancer cell lines. In tumor specimens from patients CARD8 expression has been demonstrated in colon cancer and non-small cell lung cancer. The 54-kDa CARD8 isoform has a different expression profile when compared to TUCAN/CARD8-48. For example a number of breast cancer cell lines do not express TUCAN/CARD8-54, although some of them express TUCAN/CARD8-48. Expression also varies widely among different tumor cell lines with high levels in colon cancer cells.
Localisation In MCF-7 cells overexpressed CARD8 localized to both the cytoplasmic and nuclear compartment. In specimens derived from colon cancer cells a predominant cytoplasmic expression was found, whereas in NSCLC tumor samples CARD8 was either exclusively nuclear or cytoplasmic or present in both compartments.
Function CARD8 belongs to the CARD family of proteins that play a role in apoptosis regulation and NF-kB signaling associated with the innate or adaptive immune response. For example the binding of CARDs present in caspase-9 and Apaf-1 mediate the assembly of the apoptosome in which caspase-9 is activated. CARD motifs have different binding selectivity towards each other and the presence of additional structural/ functional domains in the various CARD-containing proteins may also determine the choice of interaction partner.
In literature there is some controversy on the function of CARD8. Some reports mention an apoptosis inhibitory function of CARD8 involving its CARD-dependent binding to procaspase-9, whereas others did not find an association between CARD8 and caspase-9 and instead found either pro-apoptotic activity of CARD8 and associations with the inflammatory caspase-1 or the regulatory subunit of IkB kinase (NEMO) thereby suppressing NF-kB activation. Also an interaction between the p53-responsive gene DRAL (FLH2) and CARD8 has been reported resulting in the suppression of NF-kB activation. Furthermore, TUCAN/CARD8-54 was found to inhibit chemotherapy-induced caspase-9 activation and Fas ligand-induced caspase-8 activation. Based mainly on its proposed anti-apoptotic activity CARD8 is considered as a possible therapeutic target for cancer.
Homology CARD family proteins.


Somatic Ten single nucleotide polymorphisms (SNPs) across TUCAN/CARD8 have been identified in healthy persons and patients suffering from inflammatory bowl disease.

Implicated in

Entity Colon cancer
Prognosis TUCAN/CARD8 expression has been analyzed by immunohistochemistry in paraffin-embedded colon cancer specimens (N=102) derived from patients with clinical stage II that were surgically treated. TUCAN/CARD8 staining was stronger in colon cancer cells when compared to normal cells in 64% of the 102 specimens examined. Scoring staining intensity revealed a significant correlation between high TUCAN/CARD8 expression in tumor cells and shorter patient survival.
Entity Non-small cell lung cancer (NSCLC)
Prognosis The expression of TUCAN/CARD8 has been determined by immunohistochemistry in tumor specimens derived from NSCLC patients (N=49, stage III and IV) that received neoadjuvant or palliative chemotherapy. TUCAN/CARD8 expression was detected in 69% of the samples, showing exclusively cytoplasmic (27%) or nuclear (11%) staining, or in both compartments (31%). No correlation between response to chemotherapy or expression/ localization was found, although, cytoplasm-only staining NSCLC samples predicted shorter survival, suggesting a possible prognostic value.
Entity Inflammatory bowel disease (IBD)
Disease Crohn' disease and ulcerative colitis
Prognosis Patients with IBD (Crohn's disease (CD) and ulcerative colitis) and healthy individuals were genotyped for SNP. A significant association between a TUCAN SNP and CD was found. However, in other reports this association was not confirmed, rejecting TUCAN/CARD8 as a possible susceptibility gene for IBD.


CARD games in apoptosis and immunity.
Bouchier-Hayes L, Martin SJ
EMBO reports. 2002 ; 3 (7) : 616-621.
PMID 12101092
The expression of TUCAN, an inhibitor of apoptosis protein, in patients with advanced non-small cell lung cancer treated with chemotherapy.
Checinska A, Oudejans JJ, Span SW, Rodriguez JA, Kruyt FA, Giaccone G
Anticancer research. 2006 ; 26 (5B) : 3819-3824.
PMID 17094407
CARD proteins as therapeutic targets in cancer.
Damiano JS, Reed JC
Current drug targets. 2004 ; 5 (4) : 367-374.
PMID 15134219
Combined evidence from three large British Association studies rejects TUCAN/CARD8 as an IBD susceptibility gene.
Fisher SA, Mirza MM, Onnie CM, Soars D, Lewis CM, Prescott NJ, Mathew CG, Sanderson J, Forbes A, Todhunter C, Donaldson P, Mansfield J
Gastroenterology. 2007 ; 132 (5) : 2078-2080.
PMID 17484911
TUCAN (CARD8) genetic variants and inflammatory bowel disease.
McGovern DP, Butler H, Ahmad T, Paolucci M, van Heel DA, Negoro K, Hysi P, Ragoussis J, Travis SP, Cardon LR, Jewell DP
Gastroenterology. 2006 ; 131 (4) : 1190-1196.
PMID 17030188
TUCAN, an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancer.
Pathan N, Marusawa H, Krajewska M, Matsuzawa S, Kim H, Okada K, Torii S, Kitada S, Krajewski S, Welsh K, Pio F, Godzik A, Reed JC
The Journal of biological chemistry. 2001 ; 276 (34) : 32220-32229.
PMID 11408476
CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis.
Razmara M, Srinivasula SM, Wang L, Poyet JL, Geddes BJ, DiStefano PS, Bertin J, Alnemri ES
The Journal of biological chemistry. 2002 ; 277 (16) : 13952-13958.
PMID 11821383
TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF-kappaB activation.
Stilo R, Leonardi A, Formisano L, Di Jeso B, Vito P, Liguoro D
FEBS letters. 2002 ; 521 (1-3) : 165-169.
PMID 12067710
A novel isoform of TUCAN is overexpressed in human cancer tissues and suppresses both caspase-8- and caspase-9-mediated apoptosis.
Yamamoto M, Torigoe T, Kamiguchi K, Hirohashi Y, Nakanishi K, Nabeta C, Asanuma H, Tsuruma T, Sato T, Hata F, Ohmura T, Yamaguchi K, Kurotaki T, Hirata K, Sato N
Cancer research. 2005 ; 65 (19) : 8706-8714.
PMID 16204039
NDPP1 is a novel CARD domain containing protein which can inhibit apoptosis and suppress NF-kappaB activation.
Zhang H, Fu W
International journal of oncology. 2002 ; 20 (5) : 1035-1040.
PMID 11956601


This paper should be referenced as such :
Kruyt, Frank A
CARD8 (caspase recruitment domain family, member 8)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(4):294-296.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)CARD8   17057
Entrez_Gene (NCBI)CARD8  22900  caspase recruitment domain family member 8
GeneCards (Weizmann)CARD8
Ensembl hg19 (Hinxton)ENSG00000105483 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000105483 [Gene_View]  chr19:48208086-48241063 [Contig_View]  CARD8 [Vega]
ICGC DataPortalENSG00000105483
TCGA cBioPortalCARD8
Genatlas (Paris)CARD8
SOURCE (Princeton)CARD8
Genetics Home Reference (NIH)CARD8
Genomic and cartography
GoldenPath hg38 (UCSC)CARD8  -     chr19:48208086-48241063 -  19q13.33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CARD8  -     19q13.33   [Description]    (hg19-Feb_2009)
EnsemblCARD8 - 19q13.33 [CytoView hg19]  CARD8 - 19q13.33 [CytoView hg38]
Mapping of homologs : NCBICARD8 [Mapview hg19]  CARD8 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB023172 AF143869 AF322184 AF331519 AF405558
RefSeq transcript (Entrez)NM_001184900 NM_001184901 NM_001184902 NM_001184903 NM_001184904 NM_014959
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CARD8
Cluster EST : UnigeneHs.655940 [ NCBI ]
CGAP (NCI)Hs.655940
Alternative Splicing GalleryENSG00000105483
Gene ExpressionCARD8 [ NCBI-GEO ]   CARD8 [ EBI - ARRAY_EXPRESS ]   CARD8 [ SEEK ]   CARD8 [ MEM ]
Gene Expression Viewer (FireBrowse)CARD8 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)22900
GTEX Portal (Tissue expression)CARD8
Human Protein AtlasENSG00000105483-CARD8 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9Y2G2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9Y2G2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9Y2G2
Splice isoforms : SwissVarQ9Y2G2
Domaine pattern : Prosite (Expaxy)CARD (PS50209)   
Domains : Interpro (EBI)CARD    DEATH-like_dom    FIIND_dom   
Domain families : Pfam (Sanger)CARD (PF00619)    FIIND (PF13553)   
Domain families : Pfam (NCBI)pfam00619    pfam13553   
Conserved Domain (NCBI)CARD8
DMDM Disease mutations22900
Blocks (Seattle)CARD8
Structural Biology KnowledgeBase4IKM   
SCOP (Structural Classification of Proteins)4IKM   
CATH (Classification of proteins structures)4IKM   
Human Protein Atlas [tissue]ENSG00000105483-CARD8 [tissue]
Peptide AtlasQ9Y2G2
IPIIPI00218145   IPI00942890   IPI00032131   IPI00922017   IPI00425928   IPI00984191   IPI00974394   IPI00973940   IPI00977493   IPI00974376   IPI00974558   IPI00642708   IPI00978124   IPI00978440   IPI00977620   IPI00976952   IPI00980389   
Protein Interaction databases
IntAct (EBI)Q9Y2G2
Ontologies - Pathways
Ontology : AmiGOprotein binding  nucleus  nucleoplasm  cytoplasm  cytosol  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  cysteine-type endopeptidase activator activity involved in apoptotic process  NACHT domain binding  protein homodimerization activity  negative regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  positive regulation of interleukin-1 beta secretion  NLRP3 inflammasome complex  
Ontology : EGO-EBIprotein binding  nucleus  nucleoplasm  cytoplasm  cytosol  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  cysteine-type endopeptidase activator activity involved in apoptotic process  NACHT domain binding  protein homodimerization activity  negative regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  positive regulation of interleukin-1 beta secretion  NLRP3 inflammasome complex  
NDEx NetworkCARD8
Atlas of Cancer Signalling NetworkCARD8
Wikipedia pathwaysCARD8
Orthology - Evolution
GeneTree (enSembl)ENSG00000105483
Phylogenetic Trees/Animal Genes : TreeFamCARD8
Homologs : HomoloGeneCARD8
Homology/Alignments : Family Browser (UCSC)CARD8
Gene fusions - Rearrangements
Fusion : MitelmanCARD8/BCKDHA [19q13.33/19q13.2]  
Fusion : MitelmanCARD8/SULT2B1 [19q13.33/19q13.33]  [t(19;19)(q13;q13)]  
Fusion: TCGA_MDACCCARD8 19q13.33 BCKDHA 19q13.2 BRCA
Fusion PortalCARD8 19q13.33 BCKDHA 19q13.2 BRCA
Fusion : QuiverCARD8
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCARD8 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CARD8
Exome Variant ServerCARD8
ExAC (Exome Aggregation Consortium)ENSG00000105483
GNOMAD BrowserENSG00000105483
Genetic variants : HAPMAP22900
Genomic Variants (DGV)CARD8 [DGVbeta]
DECIPHERCARD8 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCARD8 
ICGC Data PortalCARD8 
TCGA Data PortalCARD8 
Broad Tumor PortalCARD8
OASIS PortalCARD8 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCARD8  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCARD8
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
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
BioMutasearch CARD8
DgiDB (Drug Gene Interaction Database)CARD8
DoCM (Curated mutations)CARD8 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CARD8 (select a term)
NCG5 (London)CARD8
Cancer3DCARD8(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry CARD8
NextProtQ9Y2G2 [Medical]
Target ValidationCARD8
Huge Navigator CARD8 [HugePedia]
snp3D : Map Gene to Disease22900
BioCentury BCIQCARD8
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD22900
Chemical/Pharm GKB GenePA134916154
Clinical trialCARD8
canSAR (ICR)CARD8 (select the gene name)
PubMed63 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jan 5 12:27:17 CET 2018

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