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Q9EPB4

- ASC_MOUSE

UniProt

Q9EPB4 - ASC_MOUSE

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Protein
Apoptosis-associated speck-like protein containing a CARD
Gene
Pycard, Asc
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Molecular functioni

  1. Pyrin domain binding Source: HGNC
  2. peptidase activator activity involved in apoptotic process Source: MGI
  3. protein binding Source: MGI
  4. protein homodimerization activity Source: HGNC

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  2. activation of innate immune response Source: UniProtKB
  3. apoptotic process Source: MGI
  4. cellular response to interleukin-1 Source: Ensembl
  5. cellular response to lipopolysaccharide Source: Ensembl
  6. defense response to Gram-negative bacterium Source: Ensembl
  7. defense response to virus Source: Ensembl
  8. inflammatory response Source: MGI
  9. innate immune response Source: UniProtKB-KW
  10. interleukin-1 beta production Source: MGI
  11. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: Ensembl
  12. macropinocytosis Source: UniProtKB
  13. myeloid dendritic cell activation involved in immune response Source: UniProtKB
  14. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  15. negative regulation of NF-kappaB transcription factor activity Source: Ensembl
  16. negative regulation of interferon-beta production Source: Ensembl
  17. negative regulation of protein serine/threonine kinase activity Source: Ensembl
  18. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  19. positive regulation of JNK cascade Source: Ensembl
  20. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
  21. positive regulation of T cell migration Source: UniProtKB
  22. positive regulation of actin filament polymerization Source: UniProtKB
  23. positive regulation of activated T cell proliferation Source: UniProtKB
  24. positive regulation of adaptive immune response Source: Ensembl
  25. positive regulation of antigen processing and presentation of peptide antigen via MHC class II Source: UniProtKB
  26. positive regulation of apoptotic process Source: Ensembl
  27. positive regulation of chemokine secretion Source: UniProtKB
  28. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: HGNC
  29. positive regulation of defense response to virus by host Source: UniProtKB
  30. positive regulation of extrinsic apoptotic signaling pathway Source: Ensembl
  31. positive regulation of interferon-gamma production Source: UniProtKB
  32. positive regulation of interleukin-1 beta secretion Source: UniProtKB
  33. positive regulation of interleukin-10 secretion Source: Ensembl
  34. positive regulation of interleukin-6 production Source: UniProtKB
  35. positive regulation of interleukin-6 secretion Source: Ensembl
  36. positive regulation of interleukin-8 secretion Source: Ensembl
  37. positive regulation of phagocytosis Source: UniProtKB
  38. positive regulation of release of cytochrome c from mitochondria Source: Ensembl
  39. positive regulation of tumor necrosis factor production Source: Ensembl
  40. regulation of Rac GTPase activity Source: UniProtKB
  41. regulation of apoptotic process Source: MGI
  42. regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  43. regulation of inflammatory response Source: MGI
  44. regulation of intrinsic apoptotic signaling pathway Source: Ensembl
  45. regulation of protein stability Source: UniProtKB
  46. regulation of tumor necrosis factor-mediated signaling pathway Source: Ensembl
  47. tumor necrosis factor-mediated signaling pathway Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiREACT_198662. The AIM2 inflammasome.

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptosis-associated speck-like protein containing a CARD
Short name:
mASC
Alternative name(s):
PYD and CARD domain-containing protein
Gene namesi
Name:Pycard
Synonyms:Asc
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1931465. Pycard.

Subcellular locationi

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.2 Publications

GO - Cellular componenti

  1. AIM2 inflammasome complex Source: UniProtKB
  2. NLRP1 inflammasome complex Source: Ensembl
  3. NLRP3 inflammasome complex Source: UniProtKB
  4. cytoplasm Source: HGNC
  5. cytosol Source: MGI
  6. endoplasmic reticulum Source: UniProtKB-SubCell
  7. extracellular region Source: MGI
  8. mitochondrion Source: UniProtKB-SubCell
  9. neuronal cell body Source: Ensembl
  10. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 193193Apoptosis-associated speck-like protein containing a CARD
PRO_0000064693Add
BLAST

Post-translational modificationi

Phosphorylated By similarity.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9EPB4.
PaxDbiQ9EPB4.
PRIDEiQ9EPB4.

PTM databases

PhosphoSiteiQ9EPB4.

Expressioni

Tissue specificityi

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

Developmental stagei

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

Gene expression databases

ArrayExpressiQ9EPB4.
BgeeiQ9EPB4.
CleanExiMM_PYCARD.
GenevestigatoriQ9EPB4.

Interactioni

Subunit structurei

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.1 Publication

Protein-protein interaction databases

DIPiDIP-27619N.
IntActiQ9EPB4. 3 interactions.
STRINGi10090.ENSMUSP00000033056.

Structurei

3D structure databases

ProteinModelPortaliQ9EPB4.
SMRiQ9EPB4. Positions 1-193.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 9191DAPIN
Add
BLAST
Domaini105 – 19389CARD
Add
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 CARD domain.
Contains 1 DAPIN domain.

Phylogenomic databases

eggNOGiNOG39139.
GeneTreeiENSGT00440000033973.
HOGENOMiHOG000034090.
HOVERGENiHBG018739.
InParanoidiQ9EPB4.
KOiK12799.
OMAiPMDAVDL.
OrthoDBiEOG786H4P.
PhylomeDBiQ9EPB4.
TreeFamiTF337882.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
InterProiIPR001315. CARD.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
PF02758. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
PROSITEiPS50209. CARD. 1 hit.
PS50824. DAPIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9EPB4-1 [UniParc]FASTAAdd to Basket

« Hide

MGRARDAILD ALENLSGDEL KKFKMKLLTV QLREGYGRIP RGALLQMDAI    50
DLTDKLVSYY LESYGLELTM TVLRDMGLQE LAEQLQTTKE ESGAVAAAAS 100
VPAQSTARTG HFVDQHRQAL IARVTEVDGV LDALHGSVLT EGQYQAVRAE 150
TTSQDKMRKL FSFVPSWNLT CKDSLLQALK EIHPYLVMDL EQS 193
Length:193
Mass (Da):21,459
Last modified:March 1, 2001 - v1
Checksum:i2A4EA40194870B31
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti159 – 1591K → E in BAB31341. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS21888.1.
RefSeqiNP_075747.3. NM_023258.4.
UniGeneiMm.24163.

Genome annotation databases

EnsembliENSMUST00000033056; ENSMUSP00000033056; ENSMUSG00000030793.
GeneIDi66824.
KEGGimmu:66824.
UCSCiuc009jxu.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS21888.1.
RefSeqi NP_075747.3. NM_023258.4.
UniGenei Mm.24163.

3D structure databases

ProteinModelPortali Q9EPB4.
SMRi Q9EPB4. Positions 1-193.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-27619N.
IntActi Q9EPB4. 3 interactions.
STRINGi 10090.ENSMUSP00000033056.

PTM databases

PhosphoSitei Q9EPB4.

Proteomic databases

MaxQBi Q9EPB4.
PaxDbi Q9EPB4.
PRIDEi Q9EPB4.

Protocols and materials databases

DNASUi 66824.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000033056 ; ENSMUSP00000033056 ; ENSMUSG00000030793 .
GeneIDi 66824.
KEGGi mmu:66824.
UCSCi uc009jxu.2. mouse.

Organism-specific databases

CTDi 29108.
MGIi MGI:1931465. Pycard.

Phylogenomic databases

eggNOGi NOG39139.
GeneTreei ENSGT00440000033973.
HOGENOMi HOG000034090.
HOVERGENi HBG018739.
InParanoidi Q9EPB4.
KOi K12799.
OMAi PMDAVDL.
OrthoDBi EOG786H4P.
PhylomeDBi Q9EPB4.
TreeFami TF337882.

Enzyme and pathway databases

Reactomei REACT_198662. The AIM2 inflammasome.

Miscellaneous databases

NextBioi 322743.
PROi Q9EPB4.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9EPB4.
Bgeei Q9EPB4.
CleanExi MM_PYCARD.
Genevestigatori Q9EPB4.

Family and domain databases

Gene3Di 1.10.533.10. 2 hits.
InterProi IPR001315. CARD.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
[Graphical view ]
Pfami PF00619. CARD. 1 hit.
PF02758. PYRIN. 1 hit.
[Graphical view ]
SUPFAMi SSF47986. SSF47986. 2 hits.
PROSITEi PS50209. CARD. 1 hit.
PS50824. DAPIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiASC_MOUSE
AccessioniPrimary (citable) accession number: Q9EPB4
Secondary accession number(s): Q9D2W9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: March 1, 2001
Last modified: September 3, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi