PYCARD: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''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]].<ref name="entrez">{{cite web | title = Entrez Gene: PYCARD PYD and CARD domain containing| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29108| accessdate =18 September 2010 }}</ref> It is localized mainly in the [[Cell nucleus|nucleus]] of [[Monocyte|monocytes]] and [[Macrophage|macrophages]]. In case of pathogen infection, however, it relocalizes rapidly to the [[cytoplasm]], perinuclear space, [[endoplasmic reticulum]] and [[Mitochondrion|mitochondria]] and it is a key adaptor protein in activation of the [[inflammasome]] <ref name=":0">{{Cite journal|last=Dunn|first=JH|last2=Fujita|first2=M|date=2015|title=PYCARD (PYD and CARD domain containing)|url=http://hdl.handle.net/2042/56440|journal=Atlas of Genetics and Cytogenetics in Oncology and Haematology|language=en|issue=4|doi=10.4267/2042/56440|issn=1768-3262}}</ref>.
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| update_protein_box = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
NMR structure of full-length ASC: PDB ID 2KN6 [http://www.rcsb.org/pdb/explore/explore.do?structureId=2KN6]<ref>{{Cite journal|last=Alba|first=Eva de|date=2009-11-20|title=Structure and Interdomain Dynamics of Apoptosis-associated Speck-like Protein Containing a CARD (ASC)|url=http://www.jbc.org/content/284/47/32932|journal=Journal of Biological Chemistry|language=en|volume=284|issue=47|pages=32932–32941|doi=10.1074/jbc.M109.024273|issn=0021-9258|pmc=2781708|pmid=19759015}}</ref>
{{GNF_Protein_box
| image = PBB_Protein_PYCARD_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1ucp.
| PDB = {{PDB2|1ucp}}
| Name = PYD and CARD domain containing
| HGNCid = 16608
| Symbol = PYCARD
| AltSymbols =; ASC; CARD5; MGC10332; TMS1
| OMIM = 606838
| ECnumber = 
| Homologene = 8307
| MGIid = 1931465
| GeneAtlas_image1 = PBB_GE_PYCARD_221666_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008656 |text = caspase activator activity}} {{GNF_GO|id=GO:0030693 |text = caspase activity}} {{GNF_GO|id=GO:0032090 |text = Pyrin domain binding}} {{GNF_GO|id=GO:0042803 |text = protein homodimerization activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005622 |text = intracellular}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005829 |text = cytosol}}
| Process = {{GNF_GO|id=GO:0006508 |text = proteolysis}} {{GNF_GO|id=GO:0006917 |text = induction of apoptosis}} {{GNF_GO|id=GO:0006919 |text = caspase activation}} {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0007049 |text = cell cycle}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0045786 |text = negative regulation of progression through cell cycle}} {{GNF_GO|id=GO:0050718 |text = positive regulation of interleukin-1 beta secretion}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 29108
    | Hs_Ensembl = ENSG00000103490
    | Hs_RefseqProtein = NP_037390
    | Hs_RefseqmRNA = NM_013258
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 16
    | Hs_GenLoc_start = 31120310
    | Hs_GenLoc_end = 31121512
    | Hs_Uniprot = Q9ULZ3
    | Mm_EntrezGene = 66824
    | Mm_Ensembl = ENSMUSG00000030793
    | Mm_RefseqmRNA = NM_023258
    | Mm_RefseqProtein = NP_075747
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 127783251
    | Mm_GenLoc_end = 127784895
    | Mm_Uniprot = Q54AA2
  }}
}}
'''PYD and CARD domain containing''', also known as '''PYCARD''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PYCARD PYD and CARD domain containing| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29108| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
| section_title =  
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: PYCARD PYD and CARD domain containing| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29108| accessdate = }}</ref>
}}


==References==
This gene encodes an adaptor protein that is composed of two protein–protein interaction domains: a [[N-terminus|N-terminal]] PYRIN-PAAD-DAPIN domain ([[pyrin domain|PYD]]) and a [[C-terminus|C-terminal]] caspase-recruitment domain ([[CARD 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 [[apoptosis|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.  
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Masumoto J, Taniguchi S, Ayukawa K, ''et al.'' |title=ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. |journal=J. Biol. Chem. |volume=274 |issue= 48 |pages= 33835-8 |year= 1999 |pmid= 10567338 |doi=  }}
*{{cite journal  | author=Lee SK, Na SY, Jung SY, ''et al.'' |title=Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2. |journal=Mol. Endocrinol. |volume=14 |issue= 6 |pages= 915-25 |year= 2000 |pmid= 10847592 |doi=  }}
*{{cite journal  | author=Conway KE, McConnell BB, Bowring CE, ''et al.'' |title=TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers. |journal=Cancer Res. |volume=60 |issue= 22 |pages= 6236-42 |year= 2000 |pmid= 11103776 |doi=  }}
*{{cite journal  | author=McConnell BB, Vertino PM |title=Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1. |journal=Cancer Res. |volume=60 |issue= 22 |pages= 6243-7 |year= 2000 |pmid= 11103777 |doi=  }}
*{{cite journal  | author=Martinon F, Hofmann K, Tschopp J |title=The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation. |journal=Curr. Biol. |volume=11 |issue= 4 |pages= R118-20 |year= 2001 |pmid= 11250163 |doi=  }}
*{{cite journal  | author=Geddes BJ, Wang L, Huang WJ, ''et al.'' |title=Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis. |journal=Biochem. Biophys. Res. Commun. |volume=284 |issue= 1 |pages= 77-82 |year= 2001 |pmid= 11374873 |doi= 10.1006/bbrc.2001.4928 }}
*{{cite journal  | author=Richards N, Schaner P, Diaz A, ''et al.'' |title=Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis. |journal=J. Biol. Chem. |volume=276 |issue= 42 |pages= 39320-9 |year= 2001 |pmid= 11498534 |doi= 10.1074/jbc.M104730200 }}
*{{cite journal  | author=Stimson KM, Vertino PM |title=Methylation-mediated silencing of TMS1/ASC is accompanied by histone hypoacetylation and CpG island-localized changes in chromatin architecture. |journal=J. Biol. Chem. |volume=277 |issue= 7 |pages= 4951-8 |year= 2002 |pmid= 11733524 |doi= 10.1074/jbc.M109809200 }}
*{{cite journal  | author=Manji GA, Wang L, Geddes BJ, ''et al.'' |title=PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B. |journal=J. Biol. Chem. |volume=277 |issue= 13 |pages= 11570-5 |year= 2002 |pmid= 11786556 |doi= 10.1074/jbc.M112208200 }}
*{{cite journal  | author=Srinivasula SM, Poyet JL, Razmara M, ''et al.'' |title=The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. |journal=J. Biol. Chem. |volume=277 |issue= 24 |pages= 21119-22 |year= 2002 |pmid= 11967258 |doi= 10.1074/jbc.C200179200 }}
*{{cite journal  | author=Wang L, Manji GA, Grenier JM, ''et al.'' |title=PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing. |journal=J. Biol. Chem. |volume=277 |issue= 33 |pages= 29874-80 |year= 2002 |pmid= 12019269 |doi= 10.1074/jbc.M203915200 }}
*{{cite journal  | author=Shiohara M, Taniguchi S, Masumoto J, ''et al.'' |title=ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and apoptosis in human neutrophils. |journal=Biochem. Biophys. Res. Commun. |volume=293 |issue= 5 |pages= 1314-8 |year= 2002 |pmid= 12054656 |doi= 10.1016/S0006-291X(02)00384-4 }}
*{{cite journal  | author=Martinon F, Burns K, Tschopp J |title=The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. |journal=Mol. Cell |volume=10 |issue= 2 |pages= 417-26 |year= 2002 |pmid= 12191486 |doi=  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Stehlik C, Fiorentino L, Dorfleutner A, ''et al.'' |title=The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor kappaB activation pathways. |journal=J. Exp. Med. |volume=196 |issue= 12 |pages= 1605-15 |year= 2003 |pmid= 12486103 |doi=  }}
*{{cite journal  | author=Moriai R, Tsuji N, Kobayashi D, ''et al.'' |title=A proapoptotic caspase recruitment domain protein gene, TMS1, is hypermethylated in human breast and gastric cancers. |journal=Anticancer Res. |volume=22 |issue= 6C |pages= 4163-8 |year= 2003 |pmid= 12553049 |doi=  }}
*{{cite journal  | author=Dowds TA, Masumoto J, Chen FF, ''et al.'' |title=Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product. |journal=Biochem. Biophys. Res. Commun. |volume=302 |issue= 3 |pages= 575-80 |year= 2003 |pmid= 12615073 |doi=  }}
*{{cite journal  | author=Masumoto J, Dowds TA, Schaner P, ''et al.'' |title=ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis. |journal=Biochem. Biophys. Res. Commun. |volume=303 |issue= 1 |pages= 69-73 |year= 2003 |pmid= 12646168 |doi=  }}
*{{cite journal  | author=Stehlik C, Krajewska M, Welsh K, ''et al.'' |title=The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation. |journal=Biochem. J. |volume=373 |issue= Pt 1 |pages= 101-13 |year= 2003 |pmid= 12656673 |doi= 10.1042/BJ20030304 }}
*{{cite journal  | author=Levine JJ, Stimson-Crider KM, Vertino PM |title=Effects of methylation on expression of TMS1/ASC in human breast cancer cells. |journal=Oncogene |volume=22 |issue= 22 |pages= 3475-88 |year= 2003 |pmid= 12776200 |doi= 10.1038/sj.onc.1206430 }}
}}
{{refend}}


{{protein-stub}}
PYCARD can occur in four different [[Protein isoform|isoforms]]. Isoform 1, often referred to as canonical PYCARD, and isoform 2 are the activatory isoforms. They co-localize with [[NOD-like receptor|nucleotide oligomerization domain-like receptors (NLRs)]] and [[Caspase 1|caspase-1]]. Unlike isoform 1, isoform 2 is involved in direct [[Interleukin 1 beta|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<ref name=":0" />.
{{WikiDoc Sources}}
 
== Interactions ==
 
PYCARD has been shown to [[Protein–protein interaction|interact]] with [[MEFV]].<ref name=pmid11498534>{{cite journal | vauthors = Richards N, Schaner P, Diaz A, Stuckey J, Shelden E, Wadhwa A, Gumucio DL | title = Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis | journal = J. Biol. Chem. | volume = 276 | issue = 42 | pages = 39320–9  | date = October 2001 | pmid = 11498534 | doi = 10.1074/jbc.M104730200 }}</ref>
 
== References ==
{{Reflist}}
 
== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Masumoto J, Taniguchi S, Ayukawa K, Sarvotham H, Kishino T, Niikawa N, Hidaka E, Katsuyama T, Higuchi T, Sagara J | title = ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells | journal = J. Biol. Chem. | volume = 274 | issue = 48 | pages = 33835–8 | year = 1999 | pmid = 10567338 | doi = 10.1074/jbc.274.48.33835 }}
* {{cite journal | vauthors = Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW | title = Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2 | journal = Mol. Endocrinol. | volume = 14 | issue = 6 | pages = 915–25 | year = 2000 | pmid = 10847592 | doi = 10.1210/mend.14.6.0471 }}
* {{cite journal | vauthors = Conway KE, McConnell BB, Bowring CE, Donald CD, Warren ST, Vertino PM | title = TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers | journal = Cancer Res. | volume = 60 | issue = 22 | pages = 6236–42 | year = 2000 | pmid = 11103776 | doi =  }}
* {{cite journal | vauthors = McConnell BB, Vertino PM | title = Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1 | journal = Cancer Res. | volume = 60 | issue = 22 | pages = 6243–7 | year = 2000 | pmid = 11103777 | doi =  }}
* {{cite journal | vauthors = Martinon F, Hofmann K, Tschopp J | title = The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation | journal = Curr. Biol. | volume = 11 | issue = 4 | pages = R118-20 | year = 2001 | pmid = 11250163 | doi = 10.1016/S0960-9822(01)00056-2 }}
* {{cite journal | vauthors = 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 | title = Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis | journal = Biochem. Biophys. Res. Commun. | volume = 284 | issue = 1 | pages = 77–82 | year = 2001 | pmid = 11374873 | doi = 10.1006/bbrc.2001.4928 }}
* {{cite journal | vauthors = Richards N, Schaner P, Diaz A, Stuckey J, Shelden E, Wadhwa A, Gumucio DL | title = Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis | journal = J. Biol. Chem. | volume = 276 | issue = 42 | pages = 39320–9 | year = 2001 | pmid = 11498534 | doi = 10.1074/jbc.M104730200 }}
* {{cite journal | vauthors = Stimson KM, Vertino PM | title = Methylation-mediated silencing of TMS1/ASC is accompanied by histone hypoacetylation and CpG island-localized changes in chromatin architecture | journal = J. Biol. Chem. | volume = 277 | issue = 7 | pages = 4951–8 | year = 2002 | pmid = 11733524 | doi = 10.1074/jbc.M109809200 }}
* {{cite journal | vauthors = 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 | title = PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B | journal = J. Biol. Chem. | volume = 277 | issue = 13 | pages = 11570–5 | year = 2002 | pmid = 11786556 | doi = 10.1074/jbc.M112208200 }}
* {{cite journal | vauthors = Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES | title = The PYRIN-CARD protein ASC is an activating adaptor for caspase-1 | journal = J. Biol. Chem. | volume = 277 | issue = 24 | pages = 21119–22 | year = 2002 | pmid = 11967258 | doi = 10.1074/jbc.C200179200 }}
* {{cite journal | vauthors = Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, Lora JM, Geddes BJ, Briskin M, DiStefano PS, Bertin J | title = PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing | journal = J. Biol. Chem. | volume = 277 | issue = 33 | pages = 29874–80 | year = 2002 | pmid = 12019269 | doi = 10.1074/jbc.M203915200 }}
* {{cite journal | vauthors = Shiohara M, Taniguchi S, Masumoto J, Yasui K, Koike K, Komiyama A, Sagara J | title = ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and apoptosis in human neutrophils | journal = Biochem. Biophys. Res. Commun. | volume = 293 | issue = 5 | pages = 1314–8 | year = 2002 | pmid = 12054656 | doi = 10.1016/S0006-291X(02)00384-4 }}
* {{cite journal | vauthors = Martinon F, Burns K, Tschopp J | title = The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta | journal = Mol. Cell | volume = 10 | issue = 2 | pages = 417–26 | year = 2002 | pmid = 12191486 | doi = 10.1016/S1097-2765(02)00599-3 }}
* {{cite journal | vauthors = Stehlik C, Fiorentino L, Dorfleutner A, Bruey JM, Ariza EM, Sagara J, Reed JC | title = The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor kappaB activation pathways | journal = J. Exp. Med. | volume = 196 | issue = 12 | pages = 1605–15 | year = 2002 | pmid = 12486103 | pmc = 2196065 | doi = 10.1084/jem.20021552 }}
* {{cite journal | vauthors = Moriai R, Tsuji N, Kobayashi D, Yagihashi A, Namiki Y, Takahashi H, Watanabe N | title = A proapoptotic caspase recruitment domain protein gene, TMS1, is hypermethylated in human breast and gastric cancers | journal = Anticancer Res. | volume = 22 | issue = 6C | pages = 4163–8 | year = 2003 | pmid = 12553049 | doi =  }}
* {{cite journal | vauthors = Dowds TA, Masumoto J, Chen FF, Ogura Y, Inohara N, Núñez G | title = Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product | journal = Biochem. Biophys. Res. Commun. | volume = 302 | issue = 3 | pages = 575–80 | year = 2003 | pmid = 12615073 | doi = 10.1016/S0006-291X(03)00221-3 }}
* {{cite journal | vauthors = 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 | title = ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis | journal = Biochem. Biophys. Res. Commun. | volume = 303 | issue = 1 | pages = 69–73 | year = 2003 | pmid = 12646168 | doi = 10.1016/S0006-291X(03)00309-7 }}
* {{cite journal | vauthors = Stehlik C, Krajewska M, Welsh K, Krajewski S, Godzik A, Reed JC | title = The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation | journal = Biochem. J. | volume = 373 | issue = Pt 1 | pages = 101–13 | year = 2003 | pmid = 12656673 | pmc = 1223462 | doi = 10.1042/BJ20030304 }}
* {{cite journal | vauthors = Levine JJ, Stimson-Crider KM, Vertino PM | title = Effects of methylation on expression of TMS1/ASC in human breast cancer cells | journal = Oncogene | volume = 22 | issue = 22 | pages = 3475–88 | year = 2003 | pmid = 12776200 | doi = 10.1038/sj.onc.1206430 }}
{{Refend}}
 
{{PDB Gallery|geneid=29108}}
 
 
{{Gene-16-stub}}

Latest revision as of 19:02, 7 September 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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.[1] 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 [2].

NMR structure of full-length ASC: PDB ID 2KN6 [2][3]

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[2].

Interactions

PYCARD has been shown to interact with MEFV.[4]

References

  1. "Entrez Gene: PYCARD PYD and CARD domain containing". Retrieved 18 September 2010.
  2. 2.0 2.1 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. ISSN 1768-3262.
  3. 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.
  4. 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.