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Q9EPB4 (ASC_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Apoptosis-associated speck-like protein containing a CARD

Short name=mASC
Alternative name(s):
PYD and CARD domain-containing protein
Gene names
Name:Pycard
Synonyms:Asc
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length193 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3. Involved in macrophage pyroptosis, a caspase-1-dependent inflammatory form of cell death and is the major constituent of the ASC pyroptosome which forms upon potassium depletion and rapidly recruits and activates caspase-1. In innate immune response believed to act as an integral adapter in the assembly of the inflammasome which activates caspase-1 leading to processing and secretion of proinflammatory cytokines. The function as activating adapter in different types of inflammasomes is mediated by the DAPIN and CARD domains and their homotypic interactions. Required for recruitment of caspase-1 to inflammasomes containing certain pattern recognition receptors, such as NLRP2, NLRP3, AIM2 and probably IFI16. In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1. In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation. May be involved in DDX58-triggered proinflammatory responses and inflammasome activation. In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8. In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form. Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways. For regulation of NF-kappa-B activating and inhibiting functions have been reported. Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK. Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing. Ref.5 Ref.6 Ref.7 Ref.8

Subunit structure

Self-associates; enforced oligomerization induces apoptosis, NF-kappa-B regulation and interleukin-1 beta seceretion. Homooligomers can form disk-like particles of approximately 12 nm diameter and approximately 1 nm height. Component of several inflammasomes containing one pattern recognition receptor/sensor, such as NLRP1, NLRP2, NLRP3, AIM2, MEFV or NOD2, and probably NLRC4, NLRP12 or IFI16. Major component of the ASC pyroptosome, a 1-2 um supramolecular assembly (one per macrophage cell) which consists of oligomerized PYCARD dimers and CASP1. 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. Interacts with NLRP3; the interaction requires the homooligomerization of NLRP3. Interacts with NLRP2, NLRC4, MEFV, CARD16, AIM2, IFI16, NOD2, DDX58, RIPK2, PYDC1, PYDC2, NLRP10, CASP8, CHUK, IKBKB and BAX. Ref.8

Subcellular location

Cytoplasm. Endoplasmic reticulum By similarity. Mitochondrion By similarity. Nucleus By similarity. Note: Upstream of caspase activation, a redistribution from the cytoplasm to the aggregates occurs. These appear as hollow, perinuclear spherical, ball-like structures. Upon NLRP3 inflammasome activation redistributes to the perinuclear space localizing to endoplasmic reticulum and mitochondria. Localized primarily to the nucleus in resting monocytes/macrophages and rapidly redistributed to the cytoplasm upon pathogen infection By similarity. Localized to large cytoplasmic aggregate appearing as a speck containing AIM2, PYCARD, CASP8 and bacterial DNA after infection with Francisella tularensis. Ref.7 Ref.8

Tissue specificity

Expressed in small intestine, colon, thymus, spleen, brain, heart, skeletal muscle, kidney, lung and liver.

Developmental stage

Strongly expressed at E9.5 in the telencephalon, thalamic areas of the diencephalon, heart and liver.

Domain

The DAPIN domain mediates homotypic interactions with DAPIN domains of proteins such as of NLRP3, PYDC1 and AIM2 By similarity.

The CARD domain mediates interaction with CASP1 and NLRC4 By similarity.

Post-translational modification

Phosphorylated By similarity.

Disruption phenotype

Increased resistance to endotoxic shock and severe defects in caspase-1 activation and interleukin-1 beta and interleukin-18 production in macrophages in response to several pro-inflammatory molecules. Ref.5 Ref.6

Sequence similarities

Contains 1 CARD domain.

Contains 1 DAPIN domain.

Ontologies

Keywords
   Biological processApoptosis
Immunity
Inflammatory response
Innate immunity
   Cellular componentCytoplasm
Endoplasmic reticulum
Mitochondrion
Nucleus
   DiseaseTumor suppressor
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 17008311. Source: MGI

activation of innate immune response

Inferred from mutant phenotype PubMed 19158675. Source: UniProtKB

apoptotic process

Inferred from sequence orthology Ref.1. Source: MGI

inflammatory response

Inferred from mutant phenotype Ref.6. Source: MGI

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

interleukin-1 beta production

Inferred from genetic interaction PubMed 19158679. Source: MGI

macropinocytosis

Inferred from mutant phenotype Ref.7. Source: UniProtKB

myeloid dendritic cell activation involved in immune response

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype PubMed 21487011. Source: UniProtKB

positive regulation of T cell migration

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of actin filament polymerization

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of activated T cell proliferation

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of antigen processing and presentation of peptide antigen via MHC class II

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of chemokine secretion

Inferred from mutant phenotype PubMed 21487011. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: HGNC

positive regulation of defense response to virus by host

Inferred from mutant phenotype PubMed 19158675. Source: UniProtKB

positive regulation of interferon-gamma production

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of interleukin-1 beta secretion

Inferred from mutant phenotype PubMed 19158675. Source: UniProtKB

positive regulation of interleukin-6 production

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of phagocytosis

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of Rac GTPase activity

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of apoptotic process

Inferred from mutant phenotype Ref.6. Source: MGI

regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype Ref.6. Source: MGI

regulation of inflammatory response

Inferred from mutant phenotype PubMed 22002608PubMed 22297845. Source: MGI

regulation of protein stability

Inferred from mutant phenotype Ref.7. Source: UniProtKB

   Cellular_componentAIM2 inflammasome complex

Inferred from sequence or structural similarity. Source: UniProtKB

NLRP3 inflammasome complex

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: HGNC

cytosol

Inferred from direct assay Ref.1. Source: MGI

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular region

Inferred from direct assay Ref.6. Source: MGI

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.7. Source: UniProtKB

   Molecular_functionPyrin domain binding

Inferred from sequence or structural similarity. Source: HGNC

peptidase activator activity involved in apoptotic process

Inferred from sequence orthology Ref.1. Source: MGI

protein homodimerization activity

Inferred from sequence or structural similarity. Source: HGNC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 193193Apoptosis-associated speck-like protein containing a CARD
PRO_0000064693

Regions

Domain1 – 9191DAPIN
Domain105 – 19389CARD

Experimental info

Sequence conflict1591K → E in BAB31341. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q9EPB4 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 2A4EA40194870B31

FASTA19321,459
        10         20         30         40         50         60 
MGRARDAILD ALENLSGDEL KKFKMKLLTV QLREGYGRIP RGALLQMDAI DLTDKLVSYY 

        70         80         90        100        110        120 
LESYGLELTM TVLRDMGLQE LAEQLQTTKE ESGAVAAAAS VPAQSTARTG HFVDQHRQAL 

       130        140        150        160        170        180 
IARVTEVDGV LDALHGSVLT EGQYQAVRAE TTSQDKMRKL FSFVPSWNLT CKDSLLQALK 

       190 
EIHPYLVMDL EQS 

« Hide

References

« Hide 'large scale' references
[1]"Murine ortholog of ASC, a CARD-containing protein, self-associates and exhibits restricted distribution in developing mouse embryos."
Masumoto J., Taniguchi S., Nakayama K., Ayukawa K., Sagara J.
Exp. Cell Res. 262:128-133(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
Tissue: Thymus.
[2]"Pycard a PYD and CARD containing molecule."
Martinon F., Hofmann K., Tschopp J.
Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: FVB/N.
Tissue: Mammary tumor.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Pancreas and Tongue.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"ASC is essential for LPS-induced activation of procaspase-1 independently of TLR-associated signal adaptor molecules."
Yamamoto M., Yaginuma K., Tsutsui H., Sagara J., Guan X., Seki E., Yasuda K., Yamamoto M., Akira S., Nakanishi K., Noda T., Taniguchi S.
Genes Cells 9:1055-1067(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]"Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf."
Mariathasan S., Newton K., Monack D.M., Vucic D., French D.M., Lee W.P., Roose-Girma M., Erickson S., Dixit V.M.
Nature 430:213-218(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]"The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization."
Ippagunta S.K., Malireddi R.K., Shaw P.J., Neale G.A., Walle L.V., Green D.R., Fukui Y., Lamkanfi M., Kanneganti T.D.
Nat. Immunol. 12:1010-1016(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]"AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected caspase-1-deficient macrophages."
Pierini R., Juruj C., Perret M., Jones C.L., Mangeot P., Weiss D.S., Henry T.
Cell Death Differ. 19:1709-1721(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CASP8.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB032249 mRNA. Translation: BAB16609.1.
AF310104 mRNA. Translation: AAG30287.1.
AK009852 mRNA. Translation: BAB26543.1.
AK007742 mRNA. Translation: BAB25229.1.
AK018682 mRNA. Translation: BAB31341.1.
BC008252 mRNA. Translation: AAH08252.1.
RefSeqNP_075747.3. NM_023258.4.
UniGeneMm.24163.

3D structure databases

ProteinModelPortalQ9EPB4.
SMRQ9EPB4. Positions 1-193.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-27619N.
IntActQ9EPB4. 3 interactions.
STRING10090.ENSMUSP00000033056.

PTM databases

PhosphoSiteQ9EPB4.

Proteomic databases

PaxDbQ9EPB4.
PRIDEQ9EPB4.

Protocols and materials databases

DNASU66824.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000033056; ENSMUSP00000033056; ENSMUSG00000030793.
GeneID66824.
KEGGmmu:66824.
UCSCuc009jxu.2. mouse.

Organism-specific databases

CTD29108.
MGIMGI:1931465. Pycard.

Phylogenomic databases

eggNOGNOG39139.
GeneTreeENSGT00440000033973.
HOGENOMHOG000034090.
HOVERGENHBG018739.
InParanoidQ9EPB4.
KOK12799.
OMAPMDAVDL.
OrthoDBEOG786H4P.
PhylomeDBQ9EPB4.
TreeFamTF337882.

Enzyme and pathway databases

ReactomeREACT_98458. Immune System.

Gene expression databases

ArrayExpressQ9EPB4.
BgeeQ9EPB4.
CleanExMM_PYCARD.
GenevestigatorQ9EPB4.

Family and domain databases

Gene3D1.10.533.10. 2 hits.
InterProIPR001315. CARD.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
[Graphical view]
PfamPF00619. CARD. 1 hit.
PF02758. PYRIN. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 2 hits.
PROSITEPS50209. CARD. 1 hit.
PS50824. DAPIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio322743.
PROQ9EPB4.
SOURCESearch...

Entry information

Entry nameASC_MOUSE
AccessionPrimary (citable) accession number: Q9EPB4
Secondary accession number(s): Q9D2W9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot