Recombinant Human Apoptosis-associated speck-like protein containing a CARD (PYCARD), Partial

Function

Seems to inhibit inflammasome-mediated maturation of interleukin-1 beta

Subcellular Location

Golgi apparatus membrane

Tissue Specificity

Widely expressed at low levels. Detected in peripheral blood leukocytes, lung, small intestine, spleen, thymus, colon and at lower levels in placenta, liver and kidney. Very low expression in skeletal muscle, heart and brain. Expressed in lung epithelial cells (at protein level) (PubMed:23229815). Detected in the leukemia cell lines HL-60 and U-937, but not in Jurkat T-cell lymphoma and Daudi Burkitt's lymphoma. Detected in the melanoma cell line WM35, but not in WM793. Not detected in HeLa cervical carcinoma cells and MOLT-4 lymphocytic leukemia cells

Subunit

Self-associates; enforced oligomerization induces apoptosis, NF-kappa-B regulation and interleukin-1 beta secretion (PubMed:15641782, PubMed:17599095, PubMed:33420028, PubMed:33420033, PubMed:34706239). Homooligomers can form disk-like particles of approximately 12 nm diameter and approximately 1 nm height (PubMed:15641782, PubMed:17599095). Next to isoform 1, also isoform 2 and isoform 3 may be involved in oligomerization leading to functional regulation (Probable). Component of several inflammasomes containing one pattern recognition receptor/sensor, such as NLRP1, NLRP2, NLRP3, NLRP6, NLRC4, AIM2, MEFV or NOD2, and probably NLRC4, NLRP12 or IFI16 (PubMed:11374873, PubMed:12191486, PubMed:15030775, PubMed:15456791, PubMed:19158676, PubMed:23530044, PubMed:27432880, PubMed:29440442, PubMed:30674671, PubMed:33980849, PubMed:34678144, PubMed:35559676). Major component of the ASC pyroptosome, a 1-2 um supramolecular assembly (one per macrophage cell) which consists of oligomerized PYCARD dimers and CASP1 (PubMed:17599095). Interacts with CASP1 (precursor form); the interaction induces activation of CASP1 leading to the processing of interleukin-1 beta; PYCARD competes with RIPK2 for binding to CASP1 (PubMed:11967258, PubMed:14634131, PubMed:16585594, PubMed:17599095, PubMed:33420033). Interacts with NLRP3; the interaction requires the homooligomerization of NLRP3 (PubMed:11786556, PubMed:15020601, PubMed:15030775, PubMed:34341353, PubMed:35559676). Interacts with NLRP2, NLRC4, MEFV, CARD16, AIM2, IFI16, NOD2, RIGI, RIPK2, PYDC1, PYDC2, NLRP10, CASP8, CHUK, IKBKB and BAX (PubMed:11374873, PubMed:11498534, PubMed:12486103, PubMed:12646168, PubMed:12656673, PubMed:14730312, PubMed:15096476, PubMed:15456791, PubMed:17178784, PubMed:17339483, PubMed:18362139, PubMed:19158675, PubMed:19158676, PubMed:19915568, PubMed:21575908, PubMed:23530044, PubMed:29440442, PubMed:33980849). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity). Interacts with FAM120A; this interaction inhibits inflammasome activation (PubMed:40250624)

• Masumoto J. et al. ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. — J. Biol. Chem. (1999)
• Conway K.E. et al. TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers. — Cancer Res. (2000)
• Matsushita K. et al. A splice variant of ASC regulates IL-1beta release and aggregates differently from intact ASC. — Mediators Inflamm. (2009)
• Martinon F. et al. Pycard a PYD and CARD containing molecule. (SEP-)
• Bertin J. et al. CARD5 protein is a CARD/PYRIN family member that is involved in apoptosis signal transduction. (MAY-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• McConnell B.B. et al. Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1. — Cancer Res. (2000)