ASC_HUMAN
ID ASC_HUMAN Reviewed; 195 AA.
AC Q9ULZ3; Q96D12; Q9BSZ5; Q9HBD0; Q9NXJ8;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 2.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Apoptosis-associated speck-like protein containing a CARD;
DE Short=hASC;
DE AltName: Full=Caspase recruitment domain-containing protein 5;
DE AltName: Full=PYD and CARD domain-containing protein;
DE AltName: Full=Target of methylation-induced silencing 1 {ECO:0000303|PubMed:11103777};
GN Name=PYCARD; Synonyms=ASC, CARD5, TMS1 {ECO:0000303|PubMed:11103777};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Leukemia;
RX PubMed=10567338; DOI=10.1074/jbc.274.48.33835;
RA Masumoto J., Taniguchi S., Ayukawa K., Sarvotham H., Kishino T.,
RA Niikawa N., Hidaka E., Katsuyama T., Higuchi T., Sagara J.;
RT "ASC, a novel 22-kDa protein, aggregates during apoptosis of human
RT promyelocytic leukemia HL-60 cells.";
RL J. Biol. Chem. 274:33835-33838(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Fibroblast;
RX PubMed=11103776;
RA Conway K.E., McConnell B.B., Bowring C.E., Donald C.D., Warren S.T.,
RA Vertino P.M.;
RT "TMS1, a novel proapoptotic caspase recruitment domain protein, is a target
RT of methylation-induced gene silencing in human breast cancers.";
RL Cancer Res. 60:6236-6242(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM 2), FUNCTION (ISOFORM 2), AND MASS
RP SPECTROMETRY (ISOFORM 2).
RX PubMed=19759850; DOI=10.1155/2009/287387;
RA Matsushita K., Takeoka M., Sagara J., Itano N., Kurose Y., Nakamura A.,
RA Taniguchi S.;
RT "A splice variant of ASC regulates IL-1beta release and aggregates
RT differently from intact ASC.";
RL Mediators Inflamm. 2009:287387-287387(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RA Martinon F., Hofmann K., Tschopp J.;
RT "Pycard a PYD and CARD containing molecule.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RA Bertin J.;
RT "CARD5 protein is a CARD/PYRIN family member that is involved in apoptosis
RT signal transduction.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon mucosa;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 4-195 (ISOFORM 1).
RC TISSUE=Lymph, and Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11103777;
RA McConnell B.B., Vertino P.M.;
RT "Activation of a caspase-9-mediated apoptotic pathway by subcellular
RT redistribution of the novel caspase recruitment domain protein TMS1.";
RL Cancer Res. 60:6243-6247(2000).
RN [9]
RP INTERACTION WITH NLRC4.
RX PubMed=11374873; DOI=10.1006/bbrc.2001.4928;
RA Geddes B.J., Wang L., Huang W.-J., Lavellee M., Manji G.A., Brown M.,
RA Jurman M., Cao J., Morgenstern J., Merriam S., Glucksmann M.A.,
RA DiStefano P.S., Bertin J.;
RT "Human CARD12 is a novel CED4/Apaf-1 family member that induces
RT apoptosis.";
RL Biochem. Biophys. Res. Commun. 284:77-82(2001).
RN [10]
RP INTERACTION WITH MEFV.
RX PubMed=11498534; DOI=10.1074/jbc.m104730200;
RA Richards N., Schaner P., Diaz A., Stuckey J., Shelden E., Wadhwa A.,
RA Gumucio D.L.;
RT "Interaction between pyrin and the apoptotic speck protein (ASC) modulates
RT ASC-induced apoptosis.";
RL J. Biol. Chem. 276:39320-39329(2001).
RN [11]
RP INTERACTION WITH NLRP3, AND DOMAIN.
RX PubMed=11786556; DOI=10.1074/jbc.m112208200;
RA Manji G.A., Wang L., Geddes B.J., Brown M., Merriam S., Al-Garawi A.,
RA Mak S., Lora J.M., Briskin M., Jurman M., Cao J., DiStefano P.S.,
RA Bertin J.;
RT "PYPAF1: a PYRIN-containing APAF1-like protein that assembles with ASC and
RT activates NF-kB.";
RL J. Biol. Chem. 277:11570-11575(2002).
RN [12]
RP INTERACTION WITH CASP1; NLRC4 AND CARD16.
RX PubMed=11967258; DOI=10.1074/jbc.c200179200;
RA Srinivasula S.M., Poyet J.L., Razmara M., Datta P., Zhang Z., Alnemri E.S.;
RT "The PYRIN-CARD protein ASC is an activating adaptor for caspase-1.";
RL J. Biol. Chem. 277:21119-21122(2002).
RN [13]
RP FUNCTION, AND INTERACTION WITH CHUK AND IKBKB.
RX PubMed=12486103; DOI=10.1084/jem.20021552;
RA Stehlik C., Fiorentino L., Dorfleutner A., Bruey J.M., Ariza E.M.,
RA Sagara J., Reed J.C.;
RT "The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step
RT in nuclear factor kappaB activation pathways.";
RL J. Exp. Med. 196:1605-1615(2002).
RN [14]
RP IDENTIFICATION IN NLPR1 INFLAMMASOME.
RX PubMed=12191486; DOI=10.1016/s1097-2765(02)00599-3;
RA Martinon F., Burns K., Tschopp J.;
RT "The inflammasome: a molecular platform triggering activation of
RT inflammatory caspases and processing of proIL-beta.";
RL Mol. Cell 10:417-426(2002).
RN [15]
RP FUNCTION IN APOPTOSIS, INTERACTION WITH CASP8, AND MUTAGENESIS OF LEU-12.
RX PubMed=12646168; DOI=10.1016/s0006-291x(03)00309-7;
RA Masumoto J., Dowds T.A., Schaner P., Chen F.F., Ogura Y., Li M., Zhu L.,
RA Katsuyama T., Sagara J., Taniguchi S., Gumucio D.L., Nunez G., Inohara N.;
RT "ASC is an activating adaptor for NF-kappa B and caspase-8-dependent
RT apoptosis.";
RL Biochem. Biophys. Res. Commun. 303:69-73(2003).
RN [16]
RP INTERACTION WITH PYDC1, DOMAIN, AND PHOSPHORYLATION.
RX PubMed=12656673; DOI=10.1042/bj20030304;
RA Stehlik C., Krajewska M., Welsh K., Krajewski S., Godzik A., Reed J.C.;
RT "The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated
RT nuclear-factor-kappa B and pro-caspase-1 regulation.";
RL Biochem. J. 373:101-113(2003).
RN [17]
RP INTERACTION WITH CASP1 AND RIPK2.
RX PubMed=14634131; DOI=10.4049/jimmunol.171.11.6154;
RA Stehlik C., Lee S.H., Dorfleutner A., Stassinopoulos A., Sagara J.,
RA Reed J.C.;
RT "Apoptosis-associated speck-like protein containing a caspase recruitment
RT domain is a regulator of procaspase-1 activation.";
RL J. Immunol. 171:6154-6163(2003).
RN [18]
RP FUNCTION IN NLRP2 AND NLRP3 INFLAMMASOMES, INTERACTION WITH NLRP2 AND
RP NLRP3, AND SUBCELLULAR LOCATION.
RX PubMed=15030775; DOI=10.1016/s1074-7613(04)00046-9;
RA Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N.,
RA Tschopp J.;
RT "NALP3 forms an IL-1beta-processing inflammasome with increased activity in
RT Muckle-Wells autoinflammatory disorder.";
RL Immunity 20:319-325(2004).
RN [19]
RP INTERACTION WITH NLRP10.
RX PubMed=15096476; DOI=10.1093/intimm/dxh081;
RA Wang Y., Hasegawa M., Imamura R., Kinoshita T., Kondo C., Konaka K.,
RA Suda T.;
RT "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and
RT caspase-1.";
RL Int. Immunol. 16:777-786(2004).
RN [20]
RP INTERACTION WITH NLRP3.
RX PubMed=15020601; DOI=10.1074/jbc.m401178200;
RA Dowds T.A., Masumoto J., Zhu L., Inohara N., Nunez G.;
RT "Cryopyrin-induced interleukin 1beta secretion in monocytic cells: enhanced
RT activity of disease-associated mutants and requirement for ASC.";
RL J. Biol. Chem. 279:21924-21928(2004).
RN [21]
RP INTERACTION WITH NLRP2, AND MUTAGENESIS OF GLU-13.
RX PubMed=15456791; DOI=10.1074/jbc.m406741200;
RA Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C.,
RA Reed J.C.;
RT "PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-
RT kappaB and caspase-1 activation in macrophages.";
RL J. Biol. Chem. 279:51897-51907(2004).
RN [22]
RP FUNCTION IN APOPTOSIS, SUBCELLULAR LOCATION, AND INTERACTION WITH BAX.
RX PubMed=14730312; DOI=10.1038/ncb1087;
RA Ohtsuka T., Ryu H., Minamishima Y.A., Macip S., Sagara J., Nakayama K.I.,
RA Aaronson S.A., Lee S.W.;
RT "ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis
RT pathway.";
RL Nat. Cell Biol. 6:121-128(2004).
RN [23]
RP SELF-ASSOCIATION, AND MUTAGENESIS OF ILE-8; LEU-12; GLU-13; LEU-15; GLU-19;
RP LEU-20; LYS-21; PHE-23; LEU-25; LYS-26; LEU-27; PRO-40; ARG-41; LEU-45;
RP MET-47; ASP-48; LEU-52; LEU-56; GLU-62; GLU-67; LEU-68; VAL-72 AND MET-76.
RX PubMed=15641782; DOI=10.1021/bi048374i;
RA Moriya M., Taniguchi S., Wu P., Liepinsh E., Otting G., Sagara J.;
RT "Role of charged and hydrophobic residues in the oligomerization of the
RT PYRIN domain of ASC.";
RL Biochemistry 44:575-583(2005).
RN [24]
RP ASSOCIATION WITH INFLAMMASOMES.
RX PubMed=16037825; DOI=10.1038/sj.cdd.4401734;
RA Yu J.W., Wu J., Zhang Z., Datta P., Ibrahimi I., Taniguchi S., Sagara J.,
RA Fernandes-Alnemri T., Alnemri E.S.;
RT "Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC
RT oligomerization.";
RL Cell Death Differ. 13:236-249(2006).
RN [25]
RP FUNCTION, AND INTERACTION WITH CASP1.
RX PubMed=16585594; DOI=10.4049/jimmunol.176.8.4979;
RA Sarkar A., Duncan M., Hart J., Hertlein E., Guttridge D.C., Wewers M.D.;
RT "ASC directs NF-kappaB activation by regulating receptor interacting
RT protein-2 (RIP2) caspase-1 interactions.";
RL J. Immunol. 176:4979-4986(2006).
RN [26]
RP FUNCTION.
RX PubMed=16982856; DOI=10.4049/jimmunol.177.7.4252;
RA Taxman D.J., Zhang J., Champagne C., Bergstralh D.T., Iocca H.A.,
RA Lich J.D., Ting J.P.;
RT "ASC mediates the induction of multiple cytokines by Porphyromonas
RT gingivalis via caspase-1-dependent and -independent pathways.";
RL J. Immunol. 177:4252-4256(2006).
RN [27]
RP FUNCTION, AND SUBUNIT.
RX PubMed=17599095; DOI=10.1038/sj.cdd.4402194;
RA Fernandes-Alnemri T., Wu J., Yu J.W., Datta P., Miller B., Jankowski W.,
RA Rosenberg S., Zhang J., Alnemri E.S.;
RT "The pyroptosome: a supramolecular assembly of ASC dimers mediating
RT inflammatory cell death via caspase-1 activation.";
RL Cell Death Differ. 14:1590-1604(2007).
RN [28]
RP FUNCTION IN NLRP1 INFLAMMASOME.
RX PubMed=17349957; DOI=10.1016/j.molcel.2007.01.032;
RA Faustin B., Lartigue L., Bruey J.-M., Luciano F., Sergienko E.,
RA Bailly-Maitre B., Volkmann N., Hanein D., Rouiller I., Reed J.C.;
RT "Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1
RT activation.";
RL Mol. Cell 25:713-724(2007).
RN [29]
RP FUNCTION IN APOPTOSIS.
RX PubMed=16964285; DOI=10.1038/sj.onc.1209965;
RA Hasegawa M., Kawase K., Inohara N., Imamura R., Yeh W.C., Kinoshita T.,
RA Suda T.;
RT "Mechanism of ASC-mediated apoptosis: bid-dependent apoptosis in type II
RT cells.";
RL Oncogene 26:1748-1756(2007).
RN [30]
RP INTERACTION WITH PYDC1 AND PYDC2, AND DOMAIN.
RX PubMed=17178784; DOI=10.1128/iai.01315-06;
RA Dorfleutner A., Bryan N.B., Talbott S.J., Funya K.N., Rellick S.L.,
RA Reed J.C., Shi X., Rojanasakul Y., Flynn D.C., Stehlik C.;
RT "Cellular pyrin domain-only protein 2 is a candidate regulator of
RT inflammasome activation.";
RL Infect. Immun. 75:1484-1492(2007).
RN [31]
RP INTERACTION WITH PYDC2.
RX PubMed=17339483; DOI=10.4049/jimmunol.178.6.3837;
RA Bedoya F., Sandler L.L., Harton J.A.;
RT "Pyrin-only protein 2 modulates NF-kappaB and disrupts ASC:CLR
RT interactions.";
RL J. Immunol. 178:3837-3845(2007).
RN [32]
RP INTERACTION WITH PYDC1, AND MUTAGENESIS OF GLU-13; TYR-36 AND ASP-48.
RX PubMed=18362139; DOI=10.1074/jbc.m801589200;
RA Srimathi T., Robbins S.L., Dubas R.L., Chang H., Cheng H., Roder H.,
RA Park Y.C.;
RT "Mapping of POP1-binding site on pyrin domain of ASC.";
RL J. Biol. Chem. 283:15390-15398(2008).
RN [33]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19234215; DOI=10.4049/jimmunol.0802367;
RA Bryan N.B., Dorfleutner A., Rojanasakul Y., Stehlik C.;
RT "Activation of inflammasomes requires intracellular redistribution of the
RT apoptotic speck-like protein containing a caspase recruitment domain.";
RL J. Immunol. 182:3173-3182(2009).
RN [34]
RP FUNCTION.
RX PubMed=19494289; DOI=10.4049/jimmunol.0800448;
RA Hasegawa M., Imamura R., Motani K., Nishiuchi T., Matsumoto N.,
RA Kinoshita T., Suda T.;
RT "Mechanism and repertoire of ASC-mediated gene expression.";
RL J. Immunol. 182:7655-7662(2009).
RN [35]
RP FUNCTION IN AIM2 INFLAMMASOME, INTERACTION WITH AIM2, AND DOMAIN.
RX PubMed=19158676; DOI=10.1038/nature07710;
RA Fernandes-Alnemri T., Yu J.W., Datta P., Wu J., Alnemri E.S.;
RT "AIM2 activates the inflammasome and cell death in response to cytoplasmic
RT DNA.";
RL Nature 458:509-513(2009).
RN [36]
RP FUNCTION IN AIM2 INFLAMMASOME, INTERACTION WITH AIM2, AND DOMAIN.
RX PubMed=19158675; DOI=10.1038/nature07725;
RA Hornung V., Ablasser A., Charrel-Dennis M., Bauernfeind F., Horvath G.,
RA Caffrey D.R., Latz E., Fitzgerald K.A.;
RT "AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating
RT inflammasome with ASC.";
RL Nature 458:514-518(2009).
RN [37]
RP FUNCTION (ISOFORMS 2 AND 3).
RX PubMed=20482797; DOI=10.1186/1476-9255-7-23;
RA Bryan N.B., Dorfleutner A., Kramer S.J., Yun C., Rojanasakul Y.,
RA Stehlik C.;
RT "Differential splicing of the apoptosis-associated speck like protein
RT containing a caspase recruitment domain (ASC) regulates inflammasomes.";
RL J. Inflamm. (Lond.) 7:23-23(2010).
RN [38]
RP INTERACTION WITH DDX58.
RX PubMed=19915568; DOI=10.1038/ni.1824;
RA Poeck H., Bscheider M., Gross O., Finger K., Roth S., Rebsamen M.,
RA Hannesschlager N., Schlee M., Rothenfusser S., Barchet W., Kato H.,
RA Akira S., Inoue S., Endres S., Peschel C., Hartmann G., Hornung V.,
RA Ruland J.;
RT "Recognition of RNA virus by RIG-I results in activation of CARD9 and
RT inflammasome signaling for interleukin 1 beta production.";
RL Nat. Immunol. 11:63-69(2010).
RN [39]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [40]
RP INTERACTION WITH IFI16.
RX PubMed=21575908; DOI=10.1016/j.chom.2011.04.008;
RA Kerur N., Veettil M.V., Sharma-Walia N., Bottero V., Sadagopan S.,
RA Otageri P., Chandran B.;
RT "IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in
RT response to Kaposi Sarcoma-associated herpesvirus infection.";
RL Cell Host Microbe 9:363-375(2011).
RN [41]
RP FUNCTION.
RX PubMed=21487011; DOI=10.1074/jbc.m111.221077;
RA Taxman D.J., Holley-Guthrie E.A., Huang M.T., Moore C.B., Bergstralh D.T.,
RA Allen I.C., Lei Y., Gris D., Ting J.P.;
RT "The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activated protein
RT kinase (MAPK), and chemokine induction independent of the inflammasome.";
RL J. Biol. Chem. 286:19605-19616(2011).
RN [42]
RP FUNCTION.
RX PubMed=22732093; DOI=10.1016/j.humimm.2012.06.008;
RA Guo X., Dhodapkar K.M.;
RT "Central and overlapping role of cathepsin B and inflammasome adaptor ASC
RT in antigen presenting function of human dendritic cells.";
RL Hum. Immunol. 73:871-878(2012).
RN [43]
RP SUBCELLULAR LOCATION.
RX PubMed=21124315; DOI=10.1038/nature09663;
RA Zhou R., Yazdi A.S., Menu P., Tschopp J.;
RT "A role for mitochondria in NLRP3 inflammasome activation.";
RL Nature 469:221-225(2011).
RN [44]
RP INDUCTION BY ENDOCANNABINOID ANANDAMIDE.
RX PubMed=23955712; DOI=10.1038/nm.3265;
RA Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J.,
RA Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., Czech M.P.,
RA Kunos G.;
RT "Activation of the Nlrp3 inflammasome in infiltrating macrophages by
RT endocannabinoids mediates beta cell loss in type 2 diabetes.";
RL Nat. Med. 19:1132-1140(2013).
RN [45]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION UPON HRSV (MICROBIAL
RP INFECTION).
RX PubMed=23229815; DOI=10.1136/thoraxjnl-2012-202182;
RA Triantafilou K., Kar S., Vakakis E., Kotecha S., Triantafilou M.;
RT "Human respiratory syncytial virus viroporin SH: a viral recognition
RT pathway used by the host to signal inflammasome activation.";
RL Thorax 68:66-75(2013).
RN [46]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [47]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [48]
RP FUNCTION, UBIQUITINATION AT LYS-174, MUTAGENESIS OF LYS-174, AND
RP SUBCELLULAR LOCATION.
RX PubMed=25847972; DOI=10.4049/jimmunol.1402851;
RA Guan K., Wei C., Zheng Z., Song T., Wu F., Zhang Y., Cao Y., Ma S.,
RA Chen W., Xu Q., Xia W., Gu J., He X., Zhong H.;
RT "MAVS Promotes Inflammasome Activation by Targeting ASC for K63-Linked
RT Ubiquitination via the E3 Ligase TRAF3.";
RL J. Immunol. 194:4880-4890(2015).
RN [49]
RP FUNCTION.
RX PubMed=28314590; DOI=10.1016/j.immuni.2017.02.011;
RA Wang Y., Ning X., Gao P., Wu S., Sha M., Lv M., Zhou X., Gao J., Fang R.,
RA Meng G., Su X., Jiang Z.;
RT "Inflammasome activation triggers caspase-1-mediated cleavage of cGAS to
RT regulate responses to DNA virus infection.";
RL Immunity 46:393-404(2017).
RN [50]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH 3.
RX PubMed=30674671; DOI=10.1073/pnas.1817221116;
RA Shen C., Lu A., Xie W.J., Ruan J., Negro R., Egelman E.H., Fu T.M., Wu H.;
RT "Molecular mechanism for NLRP6 inflammasome assembly and activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:2052-2057(2019).
RN [51]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NLRP6.
RX PubMed=34678144; DOI=10.1016/j.cell.2021.09.032;
RA Shen C., Li R., Negro R., Cheng J., Vora S.M., Fu T.M., Wang A., He K.,
RA Andreeva L., Gao P., Tian Z., Flavell R.A., Zhu S., Wu H.;
RT "Phase separation drives RNA virus-induced activation of the NLRP6
RT inflammasome.";
RL Cell 184:5759-5774(2021).
RN [52]
RP INTERACTION WITH NLRP3.
RX PubMed=34341353; DOI=10.1038/s41467-021-25015-6;
RA Pan P., Shen M., Yu Z., Ge W., Chen K., Tian M., Xiao F., Wang Z., Wang J.,
RA Jia Y., Wang W., Wan P., Zhang J., Chen W., Lei Z., Chen X., Luo Z.,
RA Zhang Q., Xu M., Li G., Li Y., Wu J.;
RT "SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce
RT hyperinflammation.";
RL Nat. Commun. 12:4664-4664(2021).
RN [53]
RP STRUCTURE BY NMR OF 1-91, AND DOMAIN.
RX PubMed=14499617; DOI=10.1016/j.jmb.2003.07.007;
RA Liepinsh E., Barbals R., Dahl E., Sharipo A., Staub E., Otting G.;
RT "The death-domain fold of the ASC PYRIN domain, presenting a basis for
RT PYRIN/PYRIN recognition.";
RL J. Mol. Biol. 332:1155-1163(2003).
RN [54]
RP STRUCTURE BY NMR.
RX PubMed=19759015; DOI=10.1074/jbc.m109.024273;
RA de Alba E.;
RT "Structure and interdomain dynamics of apoptosis-associated speck-like
RT protein containing a CARD (ASC).";
RL J. Biol. Chem. 284:32932-32941(2009).
RN [55] {ECO:0007744|PDB:6K99}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.10 ANGSTROMS) OF 112-194, AND SUBUNIT.
RX PubMed=33420028; DOI=10.1038/s41467-020-20319-5;
RA Gong Q., Robinson K., Xu C., Huynh P.T., Chong K.H.C., Tan E.Y.J.,
RA Zhang J., Boo Z.Z., Teo D.E.T., Lay K., Zhang Y., Lim J.S.Y., Goh W.I.,
RA Wright G., Zhong F.L., Reversade B., Wu B.;
RT "Structural basis for distinct inflammasome complex assembly by human NLRP1
RT and CARD8.";
RL Nat. Commun. 12:188-188(2021).
RN [56] {ECO:0007744|PDB:7KEU}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 113-194 IN COMPLEX
RP WITH CASP1, SUBUNIT, AND INTERACTION WITH CASP1.
RX PubMed=33420033; DOI=10.1038/s41467-020-20320-y;
RA Robert Hollingsworth L., David L., Li Y., Griswold A.R., Ruan J.,
RA Sharif H., Fontana P., Orth-He E.L., Fu T.M., Bachovchin D.A., Wu H.;
RT "Mechanism of filament formation in UPA-promoted CARD8 and NLRP1
RT inflammasomes.";
RL Nat. Commun. 12:189-189(2021).
CC -!- FUNCTION: Functions as key mediator in apoptosis and inflammation.
CC Promotes caspase-mediated apoptosis involving predominantly caspase-8
CC and also caspase-9 in a probable cell type-specific manner. Involved in
CC activation of the mitochondrial apoptotic pathway, promotes caspase-8-
CC dependent proteolytic maturation of BID independently of FADD in
CC certain cell types and also mediates mitochondrial translocation of BAX
CC and activates BAX-dependent apoptosis coupled to activation of caspase-
CC 9, -2 and -3. Involved in macrophage pyroptosis, a caspase-1-dependent
CC inflammatory form of cell death and is the major constituent of the ASC
CC pyroptosome which forms upon potassium depletion and rapidly recruits
CC and activates caspase-1. In innate immune response, acts as an integral
CC adapter in the assembly of the inflammasome which activates caspase-1
CC leading to processing and secretion of pro-inflammatory cytokines
CC (PubMed:25847972). The function as activating adapter in different
CC types of inflammasomes is mediated by the pyrin and CARD domains and
CC their homotypic interactions. Required for recruitment of caspase-1 to
CC inflammasomes containing certain pattern recognition receptors, such as
CC NLRP2, NLRP3, NLRP6, AIM2 and probably IFI16 (PubMed:15030775,
CC PubMed:17349957, PubMed:19158676, PubMed:19158675, PubMed:30674671,
CC PubMed:34678144). In the NLRP1 and NLRC4 inflammasomes seems not be
CC required but facilitates the processing of procaspase-1. In cooperation
CC with NOD2 involved in an inflammasome activated by bacterial muramyl
CC dipeptide leading to caspase-1 activation. May be involved in DDX58-
CC triggered pro-inflammatory responses and inflammasome activation. In
CC collaboration with AIM2 which detects cytosolic double-stranded DNA may
CC also be involved in a caspase-1-independent cell death that involves
CC caspase-8. In adaptive immunity may be involved in maturation of
CC dendritic cells to stimulate T-cell immunity and in cytoskeletal
CC rearrangements coupled to chemotaxis and antigen uptake may be involved
CC in post-transcriptional regulation of the guanine nucleotide exchange
CC factor DOCK2; the latter function is proposed to involve the nuclear
CC form. Also involved in transcriptional activation of cytokines and
CC chemokines independent of the inflammasome; this function may involve
CC AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways. For regulation
CC of NF-kappa-B activating and inhibiting functions have been reported.
CC Modulates NF-kappa-B induction at the level of the IKK complex by
CC inhibiting kinase activity of CHUK and IKBK. Proposed to compete with
CC RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated
CC RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta
CC processing. Modulates host resistance to DNA virus infection, probably
CC by inducing the cleavage of and inactivating CGAS in presence of
CC cytoplasmic double-stranded DNA (PubMed:28314590).
CC {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12486103,
CC ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:14499617,
CC ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:15030775,
CC ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:16964285,
CC ECO:0000269|PubMed:16982856, ECO:0000269|PubMed:17349957,
CC ECO:0000269|PubMed:17599095, ECO:0000269|PubMed:19158675,
CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19234215,
CC ECO:0000269|PubMed:19494289, ECO:0000269|PubMed:21487011,
CC ECO:0000269|PubMed:22732093, ECO:0000269|PubMed:25847972,
CC ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:30674671,
CC ECO:0000269|PubMed:34678144}.
CC -!- FUNCTION: [Isoform 2]: May have a regulating effect on the function as
CC inflammasome adapter. {ECO:0000269|PubMed:19759850,
CC ECO:0000269|PubMed:20482797}.
CC -!- FUNCTION: [Isoform 3]: Seems to inhibit inflammasome-mediated
CC maturation of interleukin-1 beta. {ECO:0000269|PubMed:20482797}.
CC -!- SUBUNIT: Self-associates; enforced oligomerization induces apoptosis,
CC NF-kappa-B regulation and interleukin-1 beta secretion
CC (PubMed:15641782, PubMed:17599095, PubMed:33420028, PubMed:33420033).
CC Homooligomers can form disk-like particles of approximately 12 nm
CC diameter and approximately 1 nm height (PubMed:15641782,
CC PubMed:17599095). Next to isoform 1, also isoform 2 and isoform 3 may
CC be involved in oligomerization leading to functional regulation
CC (Probable). Component of several inflammasomes containing one pattern
CC recognition receptor/sensor, such as NLRP1, NLRP2, NLRP3, NLRP6, NLRC4,
CC AIM2, MEFV or NOD2, and probably NLRC4, NLRP12 or IFI16
CC (PubMed:11374873, PubMed:12191486, PubMed:15030775, PubMed:15456791,
CC PubMed:19158676, PubMed:30674671, PubMed:34678144). Major component of
CC the ASC pyroptosome, a 1-2 um supramolecular assembly (one per
CC macrophage cell) which consists of oligomerized PYCARD dimers and CASP1
CC (PubMed:17599095). Interacts with CASP1 (precursor form); the
CC interaction induces activation of CASP1 leading to the processing of
CC interleukin-1 beta; PYCARD competes with RIPK2 for binding to CASP1
CC (PubMed:11967258, PubMed:14634131, PubMed:16585594, PubMed:17599095,
CC PubMed:33420033). Interacts with NLRP3; the interaction requires the
CC homooligomerization of NLRP3 (PubMed:11786556, PubMed:15030775,
CC PubMed:15020601, PubMed:34341353). Interacts with NLRP2, NLRC4, MEFV,
CC CARD16, AIM2, IFI16, NOD2, DDX58, RIPK2, PYDC1, PYDC2, NLRP10, CASP8,
CC CHUK, IKBKB and BAX (PubMed:11374873, PubMed:11498534, PubMed:12486103,
CC PubMed:12646168, PubMed:12656673, PubMed:15456791, PubMed:14730312,
CC PubMed:15096476, PubMed:17178784, PubMed:17339483, PubMed:18362139,
CC PubMed:19158675, PubMed:19158676, PubMed:19915568, PubMed:21575908).
CC Component of the AIM2 PANoptosome complex, a multiprotein complex that
CC drives inflammatory cell death (PANoptosis) (By similarity).
CC {ECO:0000250|UniProtKB:Q9EPB4, ECO:0000269|PubMed:11374873,
CC ECO:0000269|PubMed:11498534, ECO:0000269|PubMed:11786556,
CC ECO:0000269|PubMed:11967258, ECO:0000269|PubMed:12191486,
CC ECO:0000269|PubMed:12486103, ECO:0000269|PubMed:12646168,
CC ECO:0000269|PubMed:12656673, ECO:0000269|PubMed:14634131,
CC ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:15020601,
CC ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:15096476,
CC ECO:0000269|PubMed:15456791, ECO:0000269|PubMed:15641782,
CC ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:17178784,
CC ECO:0000269|PubMed:17339483, ECO:0000269|PubMed:17599095,
CC ECO:0000269|PubMed:18362139, ECO:0000269|PubMed:19158675,
CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19915568,
CC ECO:0000269|PubMed:21575908, ECO:0000269|PubMed:30674671,
CC ECO:0000269|PubMed:33420028, ECO:0000269|PubMed:33420033,
CC ECO:0000269|PubMed:34341353, ECO:0000269|PubMed:34678144, ECO:0000305}.
CC -!- INTERACTION:
CC Q9ULZ3; O14862: AIM2; NbExp=13; IntAct=EBI-751215, EBI-6253193;
CC Q9ULZ3; Q07812: BAX; NbExp=7; IntAct=EBI-751215, EBI-516580;
CC Q9ULZ3; P29466: CASP1; NbExp=9; IntAct=EBI-751215, EBI-516667;
CC Q9ULZ3; O00471: EXOC5; NbExp=5; IntAct=EBI-751215, EBI-949824;
CC Q9ULZ3; O15553: MEFV; NbExp=8; IntAct=EBI-751215, EBI-7644532;
CC Q9ULZ3; Q7RTR2: NLRC3; NbExp=3; IntAct=EBI-751215, EBI-1042625;
CC Q9ULZ3; Q9C000: NLRP1; NbExp=5; IntAct=EBI-751215, EBI-1220518;
CC Q9ULZ3; Q96P20: NLRP3; NbExp=24; IntAct=EBI-751215, EBI-6253230;
CC Q9ULZ3; Q9ULZ3: PYCARD; NbExp=8; IntAct=EBI-751215, EBI-751215;
CC Q9ULZ3; Q56P42: PYDC2; NbExp=4; IntAct=EBI-751215, EBI-6374418;
CC Q9ULZ3; Q13546: RIPK1; NbExp=2; IntAct=EBI-751215, EBI-358507;
CC Q9ULZ3; P43405: SYK; NbExp=4; IntAct=EBI-751215, EBI-78302;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11103777,
CC ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:19234215,
CC ECO:0000269|PubMed:25847972}. Inflammasome
CC {ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:15030775,
CC ECO:0000269|PubMed:30674671, ECO:0000269|PubMed:34678144}. Endoplasmic
CC reticulum {ECO:0000269|PubMed:21124315}. Mitochondrion
CC {ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:21124315}. Nucleus
CC {ECO:0000269|PubMed:19234215, ECO:0000269|PubMed:25847972}.
CC Note=Upstream of caspase activation, a redistribution from the
CC cytoplasm to the aggregates occurs. These appear as hollow, perinuclear
CC spherical, ball-like structures (PubMed:11103777, PubMed:12191486,
CC PubMed:15030775). Upon NLRP3 inflammasome activation redistributes to
CC the perinuclear space localizing to endoplasmic reticulum and
CC mitochondria (PubMed:12191486, PubMed:15030775). Localized primarily to
CC the nucleus in resting monocytes/macrophages and rapidly redistributed
CC to the cytoplasm upon pathogen infection (PubMed:19234215). Localized
CC to large cytoplasmic aggregate appearing as a speck containing AIM2,
CC PYCARD, CASP8 and bacterial DNA after infection with Francisella
CC tularensis (By similarity). {ECO:0000250|UniProtKB:Q9EPB4,
CC ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12191486,
CC ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:19234215}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:23229815}. Note=(Microbial infection) Upon HRSV
CC infection, the protein is mainly located in lipid rafts in the Golgi
CC membrane. {ECO:0000269|PubMed:23229815}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=fASC;
CC IsoId=Q9ULZ3-1; Sequence=Displayed;
CC Name=2; Synonyms=Asc-b, vASC;
CC IsoId=Q9ULZ3-2; Sequence=VSP_004119;
CC Name=3; Synonyms=Asc-c;
CC IsoId=Q9ULZ3-3; Sequence=VSP_004118;
CC -!- TISSUE SPECIFICITY: Widely expressed at low levels. Detected in
CC peripheral blood leukocytes, lung, small intestine, spleen, thymus,
CC colon and at lower levels in placenta, liver and kidney. Very low
CC expression in skeletal muscle, heart and brain. Expressed in lung
CC epithelial cells (at protein level) (PubMed:23229815). Detected in the
CC leukemia cell lines HL-60 and U-937, but not in Jurkat T-cell lymphoma
CC and Daudi Burkitt's lymphoma. Detected in the melanoma cell line WM35,
CC but not in WM793. Not detected in HeLa cervical carcinoma cells and
CC MOLT-4 lymphocytic leukemia cells. {ECO:0000269|PubMed:23229815}.
CC -!- INDUCTION: In macrophages, up-regulated by endocannabinoid
CC anandamide/AEA. {ECO:0000269|PubMed:23955712}.
CC -!- DOMAIN: The CARD domain mediates interaction with CASP1 and NLRC4
CC (PubMed:14634131 and PubMed:11967258). {ECO:0000269|PubMed:11786556}.
CC -!- DOMAIN: The pyrin domain mediates homotypic interactions with pyrin
CC domains of proteins such as of NLRP3, PYDC1, PYDC2 and AIM2.
CC {ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:12656673,
CC ECO:0000269|PubMed:14499617, ECO:0000269|PubMed:17178784,
CC ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:12656673}.
CC -!- PTM: 'Lys-63'-linked polyubiquitination by TRAF3 is critical for speck
CC formation and inflammasome activation. {ECO:0000269|PubMed:25847972}.
CC -!- MISCELLANEOUS: In breast tumorigenesis, methylation-mediated silencing
CC may affect genes and proteins that act as positive mediators of cell
CC death.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91012.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB023416; BAA87339.2; -; mRNA.
DR EMBL; AF184072; AAG01187.1; -; Genomic_DNA.
DR EMBL; AF184073; AAG01188.1; -; mRNA.
DR EMBL; AF255794; AAF99665.1; -; mRNA.
DR EMBL; AF310103; AAG30286.1; -; mRNA.
DR EMBL; AF384665; AAK63850.1; -; mRNA.
DR EMBL; AK000211; BAA91012.1; ALT_FRAME; mRNA.
DR EMBL; BC004470; AAH04470.1; -; mRNA.
DR EMBL; BC013569; AAH13569.2; -; mRNA.
DR CCDS; CCDS10708.1; -. [Q9ULZ3-1]
DR CCDS; CCDS10709.1; -. [Q9ULZ3-2]
DR RefSeq; NP_037390.2; NM_013258.4. [Q9ULZ3-1]
DR RefSeq; NP_660183.1; NM_145182.2. [Q9ULZ3-2]
DR PDB; 1UCP; NMR; -; A=1-91.
DR PDB; 2KN6; NMR; -; A=1-195.
DR PDB; 3J63; EM; 3.80 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=1-91.
DR PDB; 5H8O; X-ray; 4.21 A; B=115-195.
DR PDB; 6K99; EM; 4.10 A; A/B/C/D/E/F/G/H/I/J/K/L=112-194.
DR PDB; 6KI0; X-ray; 2.00 A; A/B=112-195.
DR PDB; 6N1H; EM; 3.17 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=112-194.
DR PDB; 7E5B; X-ray; 2.29 A; C/D=1-91.
DR PDB; 7KEU; EM; 3.90 A; A/B/C/D=113-194.
DR PDBsum; 1UCP; -.
DR PDBsum; 2KN6; -.
DR PDBsum; 3J63; -.
DR PDBsum; 5H8O; -.
DR PDBsum; 6K99; -.
DR PDBsum; 6KI0; -.
DR PDBsum; 6N1H; -.
DR PDBsum; 7E5B; -.
DR PDBsum; 7KEU; -.
DR AlphaFoldDB; Q9ULZ3; -.
DR BMRB; Q9ULZ3; -.
DR SMR; Q9ULZ3; -.
DR BioGRID; 118876; 79.
DR ComplexPortal; CPX-4082; NLRP1 inflammasome.
DR ComplexPortal; CPX-4141; NLRP3 inflammasome.
DR ComplexPortal; CPX-4142; AIM2 inflammasome.
DR ComplexPortal; CPX-4143; Pyrin inflammasome.
DR ComplexPortal; CPX-4144; NLRC4 inflammasome.
DR CORUM; Q9ULZ3; -.
DR DIP; DIP-27618N; -.
DR IntAct; Q9ULZ3; 56.
DR MINT; Q9ULZ3; -.
DR STRING; 9606.ENSP00000247470; -.
DR iPTMnet; Q9ULZ3; -.
DR PhosphoSitePlus; Q9ULZ3; -.
DR BioMuta; PYCARD; -.
DR DMDM; 18203507; -.
DR EPD; Q9ULZ3; -.
DR jPOST; Q9ULZ3; -.
DR MassIVE; Q9ULZ3; -.
DR MaxQB; Q9ULZ3; -.
DR PaxDb; Q9ULZ3; -.
DR PeptideAtlas; Q9ULZ3; -.
DR PRIDE; Q9ULZ3; -.
DR ProteomicsDB; 85158; -. [Q9ULZ3-1]
DR ProteomicsDB; 85159; -. [Q9ULZ3-2]
DR ProteomicsDB; 85160; -. [Q9ULZ3-3]
DR ABCD; Q9ULZ3; 1 sequenced antibody.
DR Antibodypedia; 3375; 744 antibodies from 45 providers.
DR DNASU; 29108; -.
DR Ensembl; ENST00000247470.10; ENSP00000247470.9; ENSG00000103490.14. [Q9ULZ3-1]
DR Ensembl; ENST00000350605.4; ENSP00000340441.4; ENSG00000103490.14. [Q9ULZ3-2]
DR GeneID; 29108; -.
DR KEGG; hsa:29108; -.
DR MANE-Select; ENST00000247470.10; ENSP00000247470.9; NM_013258.5; NP_037390.2.
DR UCSC; uc002ebm.4; human. [Q9ULZ3-1]
DR CTD; 29108; -.
DR DisGeNET; 29108; -.
DR GeneCards; PYCARD; -.
DR HGNC; HGNC:16608; PYCARD.
DR HPA; ENSG00000103490; Tissue enhanced (lymphoid tissue, skin).
DR MIM; 606838; gene.
DR neXtProt; NX_Q9ULZ3; -.
DR OpenTargets; ENSG00000103490; -.
DR PharmGKB; PA134950175; -.
DR VEuPathDB; HostDB:ENSG00000103490; -.
DR eggNOG; ENOG502S3G5; Eukaryota.
DR GeneTree; ENSGT00940000161873; -.
DR HOGENOM; CLU_113553_1_0_1; -.
DR InParanoid; Q9ULZ3; -.
DR OMA; NPAKMRK; -.
DR OrthoDB; 1494108at2759; -.
DR PhylomeDB; Q9ULZ3; -.
DR TreeFam; TF337882; -.
DR PathwayCommons; Q9ULZ3; -.
DR Reactome; R-HSA-5660668; CLEC7A/inflammasome pathway.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-844456; The NLRP3 inflammasome.
DR Reactome; R-HSA-844615; The AIM2 inflammasome.
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR SignaLink; Q9ULZ3; -.
DR SIGNOR; Q9ULZ3; -.
DR BioGRID-ORCS; 29108; 11 hits in 1084 CRISPR screens.
DR ChiTaRS; PYCARD; human.
DR EvolutionaryTrace; Q9ULZ3; -.
DR GeneWiki; PYCARD; -.
DR GenomeRNAi; 29108; -.
DR Pharos; Q9ULZ3; Tbio.
DR PRO; PR:Q9ULZ3; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9ULZ3; protein.
DR Bgee; ENSG00000103490; Expressed in monocyte and 161 other tissues.
DR ExpressionAtlas; Q9ULZ3; baseline and differential.
DR Genevisible; Q9ULZ3; HS.
DR GO; GO:0097169; C:AIM2 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0008385; C:IkappaB kinase complex; TAS:HGNC-UCL.
DR GO; GO:0061702; C:inflammasome complex; IPI:ComplexPortal.
DR GO; GO:0005874; C:microtubule; IC:ComplexPortal.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0140738; C:NLRP6 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:ARUK-UCL.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0070700; F:BMP receptor binding; IPI:AgBase.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; NAS:UniProtKB.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IPI:AgBase.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0005138; F:interleukin-6 receptor binding; IPI:AgBase.
DR GO; GO:0017024; F:myosin I binding; IPI:AgBase.
DR GO; GO:0002020; F:protease binding; IPI:AgBase.
DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC-UCL.
DR GO; GO:0032090; F:Pyrin domain binding; IPI:HGNC-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl.
DR GO; GO:0005523; F:tropomyosin binding; IPI:AgBase.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IEA:Ensembl.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; NAS:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IBA:GO_Central.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0046456; P:icosanoid biosynthetic process; IC:ComplexPortal.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0044351; P:macropinocytosis; ISS:UniProtKB.
DR GO; GO:0001773; P:myeloid dendritic cell activation; IMP:UniProtKB.
DR GO; GO:0002277; P:myeloid dendritic cell activation involved in immune response; ISS:UniProtKB.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IMP:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0032688; P:negative regulation of interferon-beta production; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007231; P:osmosensory signaling pathway; IC:ComplexPortal.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB.
DR GO; GO:0002821; P:positive regulation of adaptive immune response; IMP:UniProtKB.
DR GO; GO:0002588; P:positive regulation of antigen processing and presentation of peptide antigen via MHC class II; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:UniProtKB.
DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:HGNC-UCL.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:ComplexPortal.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:HGNC-UCL.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IMP:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IDA:UniProtKB.
DR GO; GO:0050870; P:positive regulation of T cell activation; IMP:UniProtKB.
DR GO; GO:2000406; P:positive regulation of T cell migration; ISS:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IC:ComplexPortal.
DR GO; GO:0010506; P:regulation of autophagy; IEA:Ensembl.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:2001242; P:regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:HGNC-UCL.
DR CDD; cd08330; CARD_ASC_NALP1; 1.
DR Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR033516; CARD8/ASC/NALP1_CARD.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR002398; Pept_C14.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF02758; PYRIN; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 2.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS50824; DAPIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cytoplasm;
KW Endoplasmic reticulum; Golgi apparatus; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Isopeptide bond; Membrane;
KW Mitochondrion; Nucleus; Phosphoprotein; Reference proteome;
KW Tumor suppressor; Ubl conjugation.
FT CHAIN 1..195
FT /note="Apoptosis-associated speck-like protein containing a
FT CARD"
FT /id="PRO_0000064692"
FT DOMAIN 1..91
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 107..195
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EPB4"
FT CROSSLNK 174
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25847972"
FT VAR_SEQ 26..85
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004118"
FT VAR_SEQ 93..111
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11103776"
FT /id="VSP_004119"
FT MUTAGEN 8
FT /note="I->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 12
FT /note="L->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:12646168,
FT ECO:0000269|PubMed:15641782"
FT MUTAGEN 12
FT /note="L->Q: Abolishes promotion of apoptosis and NF-kappa-
FT B activation."
FT /evidence="ECO:0000269|PubMed:12646168,
FT ECO:0000269|PubMed:15641782"
FT MUTAGEN 13
FT /note="E->A: Abolishes interaction with PYDC1."
FT /evidence="ECO:0000269|PubMed:15456791,
FT ECO:0000269|PubMed:15641782, ECO:0000269|PubMed:18362139"
FT MUTAGEN 13
FT /note="E->W: Abolishes interaction with NLRP2."
FT /evidence="ECO:0000269|PubMed:15456791,
FT ECO:0000269|PubMed:15641782, ECO:0000269|PubMed:18362139"
FT MUTAGEN 15
FT /note="L->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 19
FT /note="E->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 20
FT /note="L->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 21
FT /note="K->A,E,Q: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 23
FT /note="F->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 25
FT /note="L->A,E,G,K,N,Q: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 26
FT /note="K->A,Q: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 27
FT /note="L->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 36
FT /note="Y->A: Abolishes interaction with PYDC1."
FT /evidence="ECO:0000269|PubMed:18362139"
FT MUTAGEN 40
FT /note="P->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 41
FT /note="R->A,Q,W: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 45
FT /note="L->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 47
FT /note="M->A,N,Q: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 48
FT /note="D->A,K: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782,
FT ECO:0000269|PubMed:18362139"
FT MUTAGEN 48
FT /note="D->A: Abolishes interaction with PYDC1."
FT /evidence="ECO:0000269|PubMed:15641782,
FT ECO:0000269|PubMed:18362139"
FT MUTAGEN 52
FT /note="L->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 56
FT /note="L->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 62
FT /note="E->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 67
FT /note="E->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 68
FT /note="L->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 72
FT /note="V->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 76
FT /note="M->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:15641782"
FT MUTAGEN 174
FT /note="K->R: Loss of inflammasome activation activity."
FT /evidence="ECO:0000269|PubMed:25847972"
FT HELIX 3..14
FT /evidence="ECO:0007829|PDB:1UCP"
FT HELIX 17..26
FT /evidence="ECO:0007829|PDB:1UCP"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:1UCP"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:1UCP"
FT HELIX 41..46
FT /evidence="ECO:0007829|PDB:1UCP"
FT HELIX 49..58
FT /evidence="ECO:0007829|PDB:1UCP"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:1UCP"
FT HELIX 80..90
FT /evidence="ECO:0007829|PDB:1UCP"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:6KI0"
FT HELIX 119..125
FT /evidence="ECO:0007829|PDB:6KI0"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:6KI0"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:6KI0"
FT HELIX 143..150
FT /evidence="ECO:0007829|PDB:6KI0"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:6KI0"
FT HELIX 155..164
FT /evidence="ECO:0007829|PDB:6KI0"
FT HELIX 165..168
FT /evidence="ECO:0007829|PDB:6KI0"
FT HELIX 171..184
FT /evidence="ECO:0007829|PDB:6KI0"
FT HELIX 186..195
FT /evidence="ECO:0007829|PDB:6KI0"
SQ SEQUENCE 195 AA; 21627 MW; 455987286586F46A CRC64;
MGRARDAILD ALENLTAEEL KKFKLKLLSV PLREGYGRIP RGALLSMDAL DLTDKLVSFY
LETYGAELTA NVLRDMGLQE MAGQLQAATH QGSGAAPAGI QAPPQSAAKP GLHFIDQHRA
ALIARVTNVE WLLDALYGKV LTDEQYQAVR AEPTNPSKMR KLFSFTPAWN WTCKDLLLQA
LRESQSYLVE DLERS
