PYCARD
Apoptosis-associated speck-like protein containing a CARD
Also known as: ASC, ASC_HUMAN, CARD5, TMS-1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9ULZ3
- Gene
- PYCARD
- Ensembl
- ENSG00000103490
- Chromosome
- 16
- Canonical length
- 195 aa
- Protein class
- Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nucleoli,Cytosol
- Quaternary structure
- Homooligomer
OverviewNCBI Gene
This gene encodes an adaptor protein that is composed of two protein-protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
195 residues, UniProt reviewed canonical sequence.
>Q9ULZ3|PYCARD
1 MGRARDAILD ALENLTAEEL KKFKLKLLSV PLREGYGRIP RGALLSMDAL DLTDKLVSFY
61 LETYGAELTA NVLRDMGLQE MAGQLQAATH QGSGAAPAGI QAPPQSAAKP GLHFIDQHRA
121 ALIARVTNVE WLLDALYGKV LTDEQYQAVR AEPTNPSKMR KLFSFTPAWN WTCKDLLLQA
181 LRESQSYLVE DLERSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against PYCARD 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
- Other membrane
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.36
- Highest tissue expression
- 111 nTPM
Expression across tissuesHPA
Tissue
- skin: 111 nTPM
- spleen: 105 nTPM
- esophagus: 69 nTPM
- duodenum: 60 nTPM
- small intestine: 59 nTPM
- colon: 58 nTPM
Single-cell type
- hofbauer cells: 540 nCPM
- kupffer cells: 449 nCPM
- enterocytes: 431 nCPM
- monocytes: 363 nCPM
- esophageal suprabasal cells: 329 nCPM
- neutrophils: 328 nCPM
Immune cell
- neutrophil: 1,647 nTPM
- non-classical monocyte: 1,159 nTPM
- intermediate monocyte: 1,140 nTPM
- classical monocyte: 1,102 nTPM
- eosinophil: 951 nTPM
- myeloid DC: 831 nTPM
Brain region
- white matter: 22 nTPM
- medulla oblongata: 15 nTPM
- spinal cord: 14 nTPM
- thalamus: 13 nTPM
- pons: 12 nTPM
- hypothalamus: 9.3 nTPM
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)
- 1.9
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.4
- DepMap mean gene effect
- 0.02
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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
- apoptotic process
- apoptotic signaling pathway
- cellular response to interleukin-1
- cellular response to lipopolysaccharide
- cellular response to tumor necrosis factor
- defense response to Gram-negative bacterium
- defense response to Gram-positive bacterium
- defense response to virus
- icosanoid biosynthetic process
- inflammatory response
- innate immune response
- intrinsic apoptotic signaling pathway
- intrinsic apoptotic signaling pathway by p53 class mediator
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
- macropinocytosis
- myeloid dendritic cell activation
- myeloid dendritic cell activation involved in immune response
- negative regulation of canonical NF-kappaB signal transduction
- negative regulation of cytokine production involved in inflammatory response
- negative regulation of interferon-beta production
- negative regulation of NF-kappaB transcription factor activity
- negative regulation of protein serine/threonine kinase activity
- NLRP3 inflammasome complex assembly
- osmosensory signaling pathway
- pattern recognition receptor signaling pathway
- positive regulation of actin filament polymerization
- positive regulation of activated T cell proliferation
- positive regulation of adaptive immune response
- positive regulation of antigen processing and presentation of peptide antigen via MHC class II
- positive regulation of apoptotic process
- positive regulation of canonical NF-kappaB signal transduction
- positive regulation of chemokine production
- positive regulation of defense response to virus by host
- positive regulation of DNA-binding transcription factor activity
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of extrinsic apoptotic signaling pathway
- positive regulation of inflammatory response
- positive regulation of interleukin-1 beta production
- positive regulation of interleukin-10 production
- positive regulation of interleukin-6 production
- positive regulation of interleukin-8 production
- positive regulation of JNK cascade
- positive regulation of macrophage cytokine production
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of non-canonical NF-kappaB signal transduction
- positive regulation of phagocytosis
- positive regulation of release of cytochrome c from mitochondria
- positive regulation of T cell activation
- positive regulation of T cell migration
- positive regulation of tumor necrosis factor production
- positive regulation of type II interferon production
- protein homooligomerization
- pyroptotic inflammatory response
- regulation of autophagy
- regulation of inflammatory response
- regulation of intrinsic apoptotic signaling pathway
- regulation of protein stability
- regulation of tumor necrosis factor-mediated signaling pathway
- signal transduction
- tumor necrosis factor-mediated signaling pathway
Molecular functions
- BMP receptor binding
- cysteine-type endopeptidase activator activity
- enzyme binding
- identical protein binding
- interleukin-6 receptor binding
- pattern recognition receptor activity
- protease binding
- protein dimerization activity
- protein homodimerization activity
- protein-macromolecule adaptor activity
- Pyrin domain binding
- transmembrane transporter binding
- tropomyosin binding
- myosin I binding
Cellular components
- AIM2 inflammasome complex
- azurophil granule lumen
- canonical inflammasome complex
- cytoplasm
- cytosol
- endoplasmic reticulum
- extracellular region
- Golgi membrane
- IkappaB kinase complex
- microtubule
- mitochondrion
- neuronal cell body
- NLRP1 inflammasome complex
- NLRP3 inflammasome complex
- NLRP6 inflammasome complex
- nucleolus
- nucleoplasm
- nucleus
- protein-containing complex
- secretory granule lumen
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of PYCARD 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 PYCARD as an antibody target. Whether an autoantibody or antibody against PYCARD could matter depends on whether native PYCARD is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PYCARD 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 PYCARD as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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