CARD8
Caspase recruitment domain-containing protein 8
Also known as: CARD8_HUMAN, CARDINAL, Dakar, KIAA0955, NDPP, TUCAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9Y2G2
- Gene
- CARD8
- Ensembl
- ENSG00000105483
- Chromosome
- 19
- Canonical length
- 537 aa
- Protein class
- Disease related genes, Human disease related genes, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene belongs to the caspase recruitment domain (CARD)-containing family of proteins, which are involved in pathways leading to activation of caspases or nuclear factor kappa-B (NFKB). This protein may be a component of the inflammasome, a protein complex that plays a role in the activation of proinflammatory caspases. It is thought that this protein acts as an adaptor molecule that negatively regulates NFKB activation, CASP1-dependent IL1B secretion, and apoptosis. Polymorphisms in this gene may be associated with a susceptibility to rheumatoid arthritis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]
Canonical amino-acid sequenceUniProt
537 residues, UniProt reviewed canonical sequence.
>Q9Y2G2|CARD8
1 MEKKECPEKS SSSEEELPRR DSGSSRNIDA SKLIRLQGSR KLLVDNSIRE LQYTKTGIFF
61 QAEACVTNDT VYRELPCVSE TLCDISHFFQ EDDETEAEPL LFRAVPECQL SGGDIPSVSE
121 EQESSEGQDS GDICSEENQI VSSYASKVCF EIEEDYKNRQ FLGPEGNVDV ELIDKSTNRY
181 SVWFPTAGWY LWSATGLGFL VRDEVTVTIA FGSWSQHLAL DLQHHEQWLV GGPLFDVTAE
241 PEEAVAEIHL PHFISLQAGE VDVSWFLVAH FKNEGMVLEH PARVEPFYAV LESPSFSLMG
301 ILLRIASGTR LSIPITSNTL IYYHPHPEDI KFHLYLVPSD ALLTKAIDDE EDRFHGVRLQ
361 TSPPMEPLNF GSSYIVSNSA NLKVMPKELK LSYRSPGEIQ HFSKFYAGQM KEPIQLEITE
421 KRHGTLVWDT EVKPVDLQLV AASAPPPFSG AAFVKENHRQ LQARMGDLKG VLDDLQDNEV
481 LTENEKELVE QEKTRQSKNE ALLSMVEKKG DLALDVLFRS ISERDPYLVS YLRQQNLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CARD8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.39
- Highest tissue expression
- 37 nTPM
Expression across tissuesHPA
Tissue
- spleen: 37 nTPM
- lymph node: 36 nTPM
- tonsil: 35 nTPM
- thymus: 29 nTPM
- appendix: 27 nTPM
- adipose tissue: 26 nTPM
Single-cell type
- neutrophils: 385 nCPM
- neutrophil progenitors: 157 nCPM
- microglia: 149 nCPM
- vascular endothelial cells: 136 nCPM
- platelets: 132 nCPM
- hematopoietic stem cells: 127 nCPM
Immune cell
- neutrophil: 168 nTPM
- basophil: 105 nTPM
- eosinophil: 77 nTPM
- non-classical monocyte: 69 nTPM
- intermediate monocyte: 64 nTPM
- classical monocyte: 46 nTPM
Brain region
- thalamus: 23 nTPM
- white matter: 21 nTPM
- choroid plexus: 21 nTPM
- medulla oblongata: 21 nTPM
- spinal cord: 19 nTPM
- pons: 19 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CARD8.
Disease | AllUniProt
Conditions CARD8 is implicated in, by any mechanism.
- Inflammatory bowel disease 30 (IBD30) MIM:619079
Disease | GeneticClinVar
1 pathogenic / likely-pathogenic of 495 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Inflammatory bowel disease 30
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.88
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.92
- DepMap mean gene effect
- -0.08
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- activation of innate immune response
- antiviral innate immune response
- defense response to virus
- inflammatory response
- intrinsic apoptotic signaling pathway
- negative regulation of canonical NF-kappaB signal transduction
- negative regulation of interleukin-1 beta production
- negative regulation of lipopolysaccharide-mediated signaling pathway
- negative regulation of NLRP3 inflammasome complex assembly
- negative regulation of tumor necrosis factor-mediated signaling pathway
- positive regulation of inflammatory response
- positive regulation of interleukin-1 beta production
- protein destabilization
- regulation of apoptotic process
- self proteolysis
- CARD8 inflammasome complex assembly
Molecular functions
- CARD domain binding
- cysteine-type endopeptidase activator activity
- molecular condensate scaffold activity
- NACHT domain binding
- pattern recognition receptor activity
- peptidase activity
- protein homodimerization activity
Cellular components
- cytoplasm
- cytosol
- NLRP3 inflammasome complex
- nucleoplasm
- nucleus
- protein-containing complex
- CARD8 inflammasome complex
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CARD8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CARD8 as an antibody target. Whether an autoantibody or antibody against CARD8 could matter depends on whether native CARD8 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CARD8 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CARD8 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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