PYCARD
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPYCARD, ASC, CARD5, TMS, TMS-1, TMS1, PYD and CARD domain containing
External IDsOMIM: 606838 MGI: 1931465 HomoloGene: 8307 GeneCards: PYCARD
Orthologs
SpeciesHumanMouse
Entrez

29108

66824

Ensembl

ENSG00000103490

ENSMUSG00000030793

UniProt

Q9ULZ3

Q9EPB4

RefSeq (mRNA)

NM_145183
NM_013258
NM_145182

NM_023258

RefSeq (protein)

NP_037390
NP_660183

NP_075747

Location (UCSC)Chr 16: 31.2 – 31.2 MbChr 7: 127.59 – 127.59 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

PYCARD, often referred to as ASC (Apoptosis-associated speck-like protein containing a CARD), is a protein that in humans is encoded by the PYCARD gene.[5] It is localized mainly in the nucleus of monocytes and macrophages. In case of pathogen infection, however, it relocalizes rapidly to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria and it is a key adaptor protein in activation of the inflammasome.[6]

NMR structure of full-length ASC: PDB ID 2KN6 [7]

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.

PYCARD can occur in four different isoforms. Isoform 1, often referred to as canonical PYCARD, and isoform 2 are the activatory isoforms. They co-localize with nucleotide oligomerization domain-like receptors (NLRs) and caspase-1. Unlike isoform 1, isoform 2 is involved in direct IL-1β processing regulation. Isoform 3 is an inhibitory isoform, so that it only co-localizes with caspase-1, but not with NLRs. Isoform 4 is not able to act as an adaptor protein in NLR signalling and its role remains elusive.[6]

Interactions

PYCARD has been shown to interact with MEFV.[8]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000103490 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030793 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: PYCARD PYD and CARD domain containing". Retrieved 18 September 2010.
  6. 1 2 Dunn, JH; Fujita, M (2015). "PYCARD (PYD and CARD domain containing)". Atlas of Genetics and Cytogenetics in Oncology and Haematology (4). doi:10.4267/2042/56440. hdl:2042/56440. ISSN 1768-3262.
  7. Alba, Eva de (2009-11-20). "Structure and Interdomain Dynamics of Apoptosis-associated Speck-like Protein Containing a CARD (ASC)". Journal of Biological Chemistry. 284 (47): 32932–32941. doi:10.1074/jbc.M109.024273. ISSN 0021-9258. PMC 2781708. PMID 19759015.
  8. 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


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