PYCARD

PYD and CARD domain containing
PDB rendering based on 1ucp.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1UCP​, 2KN6​, 3J63​
Identifiers
Symbols	PYCARD ; ASC; CARD5; TMS; TMS-1; TMS1
External IDs	OMIM: 606838 MGI: 1931465 HomoloGene: 8307 GeneCards: PYCARD Gene
Gene ontology Molecular function • protease binding • interleukin-6 receptor binding • protein binding • tropomyosin binding • cysteine-type endopeptidase activator activity involved in apoptotic process • myosin I binding • enzyme binding • Pyrin domain binding • identical protein binding • protein homodimerization activity • BMP receptor binding Cellular component • extracellular region • nucleus • nucleolus • cytoplasm • mitochondrion • endoplasmic reticulum • cytosol • IkappaB kinase complex • NLRP1 inflammasome complex • NLRP3 inflammasome complex • AIM2 inflammasome complex Biological process • myeloid dendritic cell activation • activation of innate immune response • stimulatory C-type lectin receptor signaling pathway • positive regulation of defense response to virus by host • myeloid dendritic cell activation involved in immune response • positive regulation of antigen processing and presentation of peptide antigen via MHC class II • positive regulation of adaptive immune response • apoptotic process • activation of cysteine-type endopeptidase activity involved in apoptotic process • inflammatory response • signal transduction • regulation of autophagy • regulation of tumor necrosis factor-mediated signaling pathway • positive regulation of actin filament polymerization • regulation of protein stability • negative regulation of NF-kappaB transcription factor activity • interleukin-1 beta production • negative regulation of interferon-beta production • positive regulation of interferon-gamma production • positive regulation of interleukin-6 production • positive regulation of tumor necrosis factor production • tumor necrosis factor-mediated signaling pathway • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway • positive regulation of activated T cell proliferation • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • positive regulation of apoptotic process • regulation of GTPase activity • negative regulation of I-kappaB kinase/NF-kappaB signaling • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • macropinocytosis • innate immune response • positive regulation of JNK cascade • positive regulation of interleukin-1 beta secretion • regulation of inflammatory response • positive regulation of phagocytosis • defense response to Gram-negative bacterium • positive regulation of T cell activation • positive regulation of sequence-specific DNA binding transcription factor activity • positive regulation of NF-kappaB transcription factor activity • defense response to virus • positive regulation of ERK1 and ERK2 cascade • cellular response to lipopolysaccharide • cellular response to interleukin-1 • cellular response to tumor necrosis factor • negative regulation of protein serine/threonine kinase activity • intrinsic apoptotic signaling pathway by p53 class mediator • positive regulation of chemokine secretion • positive regulation of release of cytochrome c from mitochondria • positive regulation of T cell migration • positive regulation of interleukin-8 secretion • positive regulation of interleukin-6 secretion • positive regulation of cysteine-type endopeptidase activity • positive regulation of interleukin-10 secretion • positive regulation of extrinsic apoptotic signaling pathway • regulation of intrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	29108	66824
Ensembl	ENSG00000103490	ENSMUSG00000030793
UniProt	Q9ULZ3	Q9EPB4
RefSeq (mRNA)	NM_013258	NM_023258
RefSeq (protein)	NP_037390	NP_075747
Location (UCSC)	Chr 16: 31.2 – 31.2 Mb	Chr 7: 127.99 – 127.99 Mb
PubMed search

Apoptosis-associated speck-like protein containing a CARD or ASC is a protein that in humans is encoded by the PYCARD gene.^[1]

Function

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.^[1]

Interactions

PYCARD has been shown to interact with MEFV.^[2]

References

1. "Entrez Gene: PYCARD PYD and CARD domain containing". Retrieved 18 September 2010.
2. Richards N, Schaner P, Diaz A, Stuckey J, Shelden E, Wadhwa A, Gumucio DL (October 2001). "Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis". J. Biol. Chem. 276 (42): 39320–9. doi:10.1074/jbc.M104730200. PMID 11498534.

Further reading

• Masumoto J, Taniguchi S, Ayukawa K, Sarvotham H, Kishino T, Niikawa N, Hidaka E, Katsuyama T, Higuchi T, Sagara J (1999). "ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells". J. Biol. Chem. 274 (48): 33835–8. doi:10.1074/jbc.274.48.33835. PMID 10567338.
• Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW (2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Mol. Endocrinol. 14 (6): 915–25. doi:10.1210/mend.14.6.0471. PMID 10847592.
• Conway KE, McConnell BB, Bowring CE, Donald CD, Warren ST, Vertino PM (2000). "TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers". Cancer Res. 60 (22): 6236–42. PMID 11103776.
• McConnell BB, Vertino PM (2000). "Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1". Cancer Res. 60 (22): 6243–7. PMID 11103777.
• Martinon F, Hofmann K, Tschopp J (2001). "The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation". Curr. Biol. 11 (4): R118–20. doi:10.1016/S0960-9822(01)00056-2. PMID 11250163.
• Geddes BJ, Wang L, Huang WJ, Lavellee M, Manji GA, Brown M, Jurman M, Cao J, Morgenstern J, Merriam S, Glucksmann MA, DiStefano PS, Bertin J (2001). "Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis". Biochem. Biophys. Res. Commun. 284 (1): 77–82. doi:10.1006/bbrc.2001.4928. PMID 11374873.
• Richards N, Schaner P, Diaz A, Stuckey J, Shelden E, Wadhwa A, Gumucio DL (2001). "Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis". J. Biol. Chem. 276 (42): 39320–9. doi:10.1074/jbc.M104730200. PMID 11498534.
• Stimson KM, Vertino PM (2002). "Methylation-mediated silencing of TMS1/ASC is accompanied by histone hypoacetylation and CpG island-localized changes in chromatin architecture". J. Biol. Chem. 277 (7): 4951–8. doi:10.1074/jbc.M109809200. PMID 11733524.
• Manji GA, Wang L, Geddes BJ, Brown M, Merriam S, Al-Garawi A, Mak S, Lora JM, Briskin M, Jurman M, Cao J, DiStefano PS, Bertin J (2002). "PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B". J. Biol. Chem. 277 (13): 11570–5. doi:10.1074/jbc.M112208200. PMID 11786556.
• Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES (2002). "The PYRIN-CARD protein ASC is an activating adaptor for caspase-1". J. Biol. Chem. 277 (24): 21119–22. doi:10.1074/jbc.C200179200. PMID 11967258.
• Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, Lora JM, Geddes BJ, Briskin M, DiStefano PS, Bertin J (2002). "PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing". J. Biol. Chem. 277 (33): 29874–80. doi:10.1074/jbc.M203915200. PMID 12019269.
• Shiohara M, Taniguchi S, Masumoto J, Yasui K, Koike K, Komiyama A, Sagara J (2002). "ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and apoptosis in human neutrophils". Biochem. Biophys. Res. Commun. 293 (5): 1314–8. doi:10.1016/S0006-291X(02)00384-4. PMID 12054656.
• Martinon F, Burns K, Tschopp J (2002). "The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta". Mol. Cell 10 (2): 417–26. doi:10.1016/S1097-2765(02)00599-3. PMID 12191486.
• Stehlik C, Fiorentino L, Dorfleutner A, Bruey JM, Ariza EM, Sagara J, Reed JC (2002). "The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor kappaB activation pathways". J. Exp. Med. 196 (12): 1605–15. doi:10.1084/jem.20021552. PMC 2196065. PMID 12486103.
• Moriai R, Tsuji N, Kobayashi D, Yagihashi A, Namiki Y, Takahashi H, Watanabe N (2003). "A proapoptotic caspase recruitment domain protein gene, TMS1, is hypermethylated in human breast and gastric cancers". Anticancer Res. 22 (6C): 4163–8. PMID 12553049.
• Dowds TA, Masumoto J, Chen FF, Ogura Y, Inohara N, Núñez G (2003). "Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product". Biochem. Biophys. Res. Commun. 302 (3): 575–80. doi:10.1016/S0006-291X(03)00221-3. PMID 12615073.
• Masumoto J, Dowds TA, Schaner P, Chen FF, Ogura Y, Li M, Zhu L, Katsuyama T, Sagara J, Taniguchi S, Gumucio DL, Núñez G, Inohara N (2003). "ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis". Biochem. Biophys. Res. Commun. 303 (1): 69–73. doi:10.1016/S0006-291X(03)00309-7. PMID 12646168.
• Stehlik C, Krajewska M, Welsh K, Krajewski S, Godzik A, Reed JC (2003). "The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation". Biochem. J. 373 (Pt 1): 101–13. doi:10.1042/BJ20030304. PMC 1223462. PMID 12656673.
• Levine JJ, Stimson-Crider KM, Vertino PM (2003). "Effects of methylation on expression of TMS1/ASC in human breast cancer cells". Oncogene 22 (22): 3475–88. doi:10.1038/sj.onc.1206430. PMID 12776200.