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Q9ULZ3

- ASC_HUMAN

UniProt

Q9ULZ3 - ASC_HUMAN

Protein

Apoptosis-associated speck-like protein containing a CARD

Gene

PYCARD

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 2 (01 Mar 2001)
      Previous versions | rss
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    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. Isoform 2 may have a regulating effect on the function as inflammasome adapter. Isoform 3 seems to inhibit inflammasome-mediated maturation of interleukin-1 beta. 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.17 Publications

    GO - Molecular functioni

    1. cysteine-type endopeptidase activator activity involved in apoptotic process Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. protein homodimerization activity Source: HGNC
    4. Pyrin domain binding Source: HGNC

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    2. activation of innate immune response Source: UniProtKB
    3. apoptotic process Source: ProtInc
    4. cellular response to interleukin-1 Source: UniProtKB
    5. cellular response to lipopolysaccharide Source: UniProtKB
    6. cellular response to tumor necrosis factor Source: UniProtKB
    7. defense response to Gram-negative bacterium Source: UniProtKB
    8. defense response to virus Source: UniProtKB
    9. inflammatory response Source: UniProtKB-KW
    10. innate immune response Source: Reactome
    11. interleukin-1 beta production Source: Ensembl
    12. intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
    13. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
    14. macropinocytosis Source: UniProtKB
    15. myeloid dendritic cell activation Source: UniProtKB
    16. myeloid dendritic cell activation involved in immune response Source: UniProtKB
    17. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    18. negative regulation of interferon-beta production Source: UniProtKB
    19. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
    20. negative regulation of protein serine/threonine kinase activity Source: UniProtKB
    21. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
    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: UniProtKB
    25. positive regulation of antigen processing and presentation of peptide antigen via MHC class II Source: UniProtKB
    26. positive regulation of apoptotic process Source: UniProtKB
    27. positive regulation of chemokine secretion Source: UniProtKB
    28. positive regulation of cysteine-type endopeptidase activity Source: UniProtKB
    29. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: HGNC
    30. positive regulation of defense response to virus by host Source: Ensembl
    31. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    32. positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
    33. positive regulation of interferon-gamma production Source: UniProtKB
    34. positive regulation of interleukin-10 secretion Source: UniProtKB
    35. positive regulation of interleukin-1 beta secretion Source: HGNC
    36. positive regulation of interleukin-6 production Source: UniProtKB
    37. positive regulation of interleukin-6 secretion Source: UniProtKB
    38. positive regulation of interleukin-8 secretion Source: UniProtKB
    39. positive regulation of JNK cascade Source: UniProtKB
    40. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    41. positive regulation of phagocytosis Source: UniProtKB
    42. positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
    43. positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
    44. positive regulation of T cell activation Source: UniProtKB
    45. positive regulation of T cell migration Source: UniProtKB
    46. positive regulation of tumor necrosis factor production Source: UniProtKB
    47. regulation of inflammatory response Source: Ensembl
    48. regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
    49. regulation of protein stability Source: UniProtKB
    50. regulation of Rac GTPase activity Source: Ensembl
    51. regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
    52. signal transduction Source: UniProtKB
    53. tumor necrosis factor-mediated signaling pathway Source: HGNC

    Keywords - Biological processi

    Apoptosis, Immunity, Inflammatory response, Innate immunity

    Enzyme and pathway databases

    ReactomeiREACT_75777. The AIM2 inflammasome.
    REACT_75808. The NLRP3 inflammasome.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Apoptosis-associated speck-like protein containing a CARD
    Short name:
    hASC
    Alternative name(s):
    Caspase recruitment domain-containing protein 5
    PYD and CARD domain-containing protein
    Target of methylation-induced silencing 1
    Gene namesi
    Name:PYCARD
    Synonyms:ASC, CARD5, TMS1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:16608. PYCARD.

    Subcellular locationi

    Cytoplasm. Endoplasmic reticulum. Mitochondrion. Nucleus
    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. Localized to large cytoplasmic aggregate appearing as a speck containing AIM2, PYCARD, CASP8 and bacterial DNA after infection with Francisella tularensis By similarity.By similarity

    GO - Cellular componenti

    1. AIM2 inflammasome complex Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: Reactome
    4. endoplasmic reticulum Source: UniProtKB-SubCell
    5. extracellular region Source: Ensembl
    6. IkappaB kinase complex Source: HGNC
    7. mitochondrion Source: UniProtKB
    8. neuronal cell body Source: Ensembl
    9. NLRP1 inflammasome complex Source: UniProtKB
    10. NLRP3 inflammasome complex Source: UniProtKB
    11. nucleolus Source: HPA
    12. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Mitochondrion, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi8 – 81I → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi12 – 121L → A: Abolishes homooligomerization. 2 Publications
    Mutagenesisi12 – 121L → Q: Abolishes promotion of apoptosis and NF-kappa-B activation. 2 Publications
    Mutagenesisi13 – 131E → A: Abolishes interaction with PYDC1. 3 Publications
    Mutagenesisi13 – 131E → W: Abolishes interaction with NLRP2. 3 Publications
    Mutagenesisi15 – 151L → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi19 – 191E → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi20 – 201L → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi21 – 211K → A, E or Q: Abolishes homooligomerization. 1 Publication
    Mutagenesisi23 – 231F → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi25 – 251L → A, E, G, K, N or Q: Abolishes homooligomerization. 1 Publication
    Mutagenesisi26 – 261K → A or Q: Abolishes homooligomerization. 1 Publication
    Mutagenesisi27 – 271L → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi36 – 361Y → A: Abolishes interaction with PYDC1. 1 Publication
    Mutagenesisi40 – 401P → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi41 – 411R → A, Q or W: Abolishes homooligomerization. 1 Publication
    Mutagenesisi45 – 451L → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi47 – 471M → A, N or Q: Abolishes homooligomerization. 1 Publication
    Mutagenesisi48 – 481D → A or K: Abolishes homooligomerization. 2 Publications
    Mutagenesisi48 – 481D → A: Abolishes interaction with PYDC1. 2 Publications
    Mutagenesisi52 – 521L → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi56 – 561L → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi62 – 621E → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi67 – 671E → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi68 – 681L → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi72 – 721V → A: Abolishes homooligomerization. 1 Publication
    Mutagenesisi76 – 761M → A: Abolishes homooligomerization. 1 Publication

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    PharmGKBiPA134950175.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 195195Apoptosis-associated speck-like protein containing a CARDPRO_0000064692Add
    BLAST

    Post-translational modificationi

    Phosphorylated.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9ULZ3.
    PaxDbiQ9ULZ3.
    PRIDEiQ9ULZ3.

    PTM databases

    PhosphoSiteiQ9ULZ3.

    Expressioni

    Tissue specificityi

    Widely expressed at low levels. Detected in peripheral blood leukocytes, lung, small intestine, spleen, thymus, colon and at lower levels in placenta, liver and kidney. Very low expression in skeletal muscle, heart and brain. Detected in the leukemia cell lines HL-60 and U-937, but not in Jurkat T-cell lymphoma and Daudi Burkitt's lymphoma. Detected in the melanoma cell line WM35, but not in WM793. Not detected in HeLa cervical carcinoma cells and MOLT-4 lymphocytic leukemia cells.

    Gene expression databases

    ArrayExpressiQ9ULZ3.
    BgeeiQ9ULZ3.
    CleanExiHS_PYCARD.
    GenevestigatoriQ9ULZ3.

    Organism-specific databases

    HPAiCAB006853.
    CAB015948.
    HPA049074.

    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. Next to isorm 1 also isoform 2 and isoform 3 may be involved in oligomerization leading to functional regulation. 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.23 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AIM2O148625EBI-751215,EBI-6253193
    BAXQ078127EBI-751215,EBI-516580
    NLRP1Q9C0005EBI-751215,EBI-1220518
    NLRP3Q96P204EBI-751215,EBI-6253230
    PYDC2Q56P424EBI-751215,EBI-6374418

    Protein-protein interaction databases

    BioGridi118876. 11 interactions.
    DIPiDIP-27618N.
    IntActiQ9ULZ3. 21 interactions.
    MINTiMINT-206960.
    STRINGi9606.ENSP00000247470.

    Structurei

    Secondary structure

    1
    195
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 1412
    Helixi17 – 2610
    Turni27 – 293
    Beta strandi34 – 363
    Helixi41 – 466
    Helixi49 – 5810
    Helixi62 – 7514
    Helixi80 – 9011
    Helixi117 – 12610
    Helixi129 – 1357
    Turni136 – 1405
    Helixi143 – 1508
    Helixi155 – 16410
    Helixi166 – 1683
    Helixi171 – 18414
    Helixi186 – 1938

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1UCPNMR-A1-91[»]
    2KN6NMR-A1-195[»]
    3J63electron microscopy3.80A/B/C/D/E/F/G/H/I/J/K/L/M/N/O1-91[»]
    ProteinModelPortaliQ9ULZ3.
    SMRiQ9ULZ3. Positions 1-195.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9ULZ3.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 9191DAPINPROSITE-ProRule annotationAdd
    BLAST
    Domaini107 – 19589CARDPROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The DAPIN domain mediates homotypic interactions with DAPIN domains of proteins such as of NLRP3, PYDC1 and AIM2 (PubMed:11786556, PubMed:12656673, PubMed:19158676 and PubMed:19158675).1 Publication
    The CARD domain mediates interaction with CASP1 and NLRC4 (PubMed:14634131 and PubMed:11967258).1 Publication

    Sequence similaritiesi

    Contains 1 CARD domain.PROSITE-ProRule annotation
    Contains 1 DAPIN domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG39139.
    HOGENOMiHOG000034090.
    HOVERGENiHBG018739.
    InParanoidiQ9ULZ3.
    KOiK12799.
    OMAiPMDAVDL.
    OrthoDBiEOG786H4P.
    PhylomeDBiQ9ULZ3.
    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]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9ULZ3-1) [UniParc]FASTAAdd to Basket

    Also known as: fASC

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGRARDAILD ALENLTAEEL KKFKLKLLSV PLREGYGRIP RGALLSMDAL    50
    DLTDKLVSFY LETYGAELTA NVLRDMGLQE MAGQLQAATH QGSGAAPAGI 100
    QAPPQSAAKP GLHFIDQHRA ALIARVTNVE WLLDALYGKV LTDEQYQAVR 150
    AEPTNPSKMR KLFSFTPAWN WTCKDLLLQA LRESQSYLVE DLERS 195
    Length:195
    Mass (Da):21,627
    Last modified:March 1, 2001 - v2
    Checksum:i455987286586F46A
    GO
    Isoform 2 (identifier: Q9ULZ3-2) [UniParc]FASTAAdd to Basket

    Also known as: Asc-b, vASC

    The sequence of this isoform differs from the canonical sequence as follows:
         93-111: Missing.

    Show »
    Length:176
    Mass (Da):19,969
    Checksum:iC4AB645696FA115D
    GO
    Isoform 3 (identifier: Q9ULZ3-3) [UniParc]FASTAAdd to Basket

    Also known as: Asc-c

    The sequence of this isoform differs from the canonical sequence as follows:
         26-85: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:135
    Mass (Da):15,030
    Checksum:iF46DB2DF379E95E9
    GO

    Sequence cautioni

    The sequence BAA91012.1 differs from that shown. Reason: Frameshift at position 4.

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei26 – 8560Missing in isoform 3. 1 PublicationVSP_004118Add
    BLAST
    Alternative sequencei93 – 11119Missing in isoform 2. 1 PublicationVSP_004119Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB023416 mRNA. Translation: BAA87339.2.
    AF184072 Genomic DNA. Translation: AAG01187.1.
    AF184073 mRNA. Translation: AAG01188.1.
    AF255794 mRNA. Translation: AAF99665.1.
    AF310103 mRNA. Translation: AAG30286.1.
    AF384665 mRNA. Translation: AAK63850.1.
    AK000211 mRNA. Translation: BAA91012.1. Frameshift.
    BC004470 mRNA. Translation: AAH04470.1.
    BC013569 mRNA. Translation: AAH13569.2.
    CCDSiCCDS10708.1. [Q9ULZ3-1]
    CCDS10709.1. [Q9ULZ3-2]
    RefSeqiNP_037390.2. NM_013258.4. [Q9ULZ3-1]
    NP_660183.1. NM_145182.2. [Q9ULZ3-2]
    UniGeneiHs.499094.

    Genome annotation databases

    EnsembliENST00000247470; ENSP00000247470; ENSG00000103490. [Q9ULZ3-1]
    ENST00000350605; ENSP00000340441; ENSG00000103490. [Q9ULZ3-2]
    GeneIDi29108.
    KEGGihsa:29108.
    UCSCiuc002ebm.3. human. [Q9ULZ3-2]
    uc010cak.3. human. [Q9ULZ3-1]

    Polymorphism databases

    DMDMi18203507.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB023416 mRNA. Translation: BAA87339.2 .
    AF184072 Genomic DNA. Translation: AAG01187.1 .
    AF184073 mRNA. Translation: AAG01188.1 .
    AF255794 mRNA. Translation: AAF99665.1 .
    AF310103 mRNA. Translation: AAG30286.1 .
    AF384665 mRNA. Translation: AAK63850.1 .
    AK000211 mRNA. Translation: BAA91012.1 . Frameshift.
    BC004470 mRNA. Translation: AAH04470.1 .
    BC013569 mRNA. Translation: AAH13569.2 .
    CCDSi CCDS10708.1. [Q9ULZ3-1 ]
    CCDS10709.1. [Q9ULZ3-2 ]
    RefSeqi NP_037390.2. NM_013258.4. [Q9ULZ3-1 ]
    NP_660183.1. NM_145182.2. [Q9ULZ3-2 ]
    UniGenei Hs.499094.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1UCP NMR - A 1-91 [» ]
    2KN6 NMR - A 1-195 [» ]
    3J63 electron microscopy 3.80 A/B/C/D/E/F/G/H/I/J/K/L/M/N/O 1-91 [» ]
    ProteinModelPortali Q9ULZ3.
    SMRi Q9ULZ3. Positions 1-195.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 118876. 11 interactions.
    DIPi DIP-27618N.
    IntActi Q9ULZ3. 21 interactions.
    MINTi MINT-206960.
    STRINGi 9606.ENSP00000247470.

    PTM databases

    PhosphoSitei Q9ULZ3.

    Polymorphism databases

    DMDMi 18203507.

    Proteomic databases

    MaxQBi Q9ULZ3.
    PaxDbi Q9ULZ3.
    PRIDEi Q9ULZ3.

    Protocols and materials databases

    DNASUi 29108.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000247470 ; ENSP00000247470 ; ENSG00000103490 . [Q9ULZ3-1 ]
    ENST00000350605 ; ENSP00000340441 ; ENSG00000103490 . [Q9ULZ3-2 ]
    GeneIDi 29108.
    KEGGi hsa:29108.
    UCSCi uc002ebm.3. human. [Q9ULZ3-2 ]
    uc010cak.3. human. [Q9ULZ3-1 ]

    Organism-specific databases

    CTDi 29108.
    GeneCardsi GC16M031212.
    H-InvDB HIX0012985.
    HGNCi HGNC:16608. PYCARD.
    HPAi CAB006853.
    CAB015948.
    HPA049074.
    MIMi 606838. gene.
    neXtProti NX_Q9ULZ3.
    PharmGKBi PA134950175.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG39139.
    HOGENOMi HOG000034090.
    HOVERGENi HBG018739.
    InParanoidi Q9ULZ3.
    KOi K12799.
    OMAi PMDAVDL.
    OrthoDBi EOG786H4P.
    PhylomeDBi Q9ULZ3.
    TreeFami TF337882.

    Enzyme and pathway databases

    Reactomei REACT_75777. The AIM2 inflammasome.
    REACT_75808. The NLRP3 inflammasome.

    Miscellaneous databases

    ChiTaRSi PYCARD. human.
    EvolutionaryTracei Q9ULZ3.
    GeneWikii PYCARD.
    GenomeRNAii 29108.
    NextBioi 52169.
    PROi Q9ULZ3.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9ULZ3.
    Bgeei Q9ULZ3.
    CleanExi HS_PYCARD.
    Genevestigatori Q9ULZ3.

    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

    1. "ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells."
      Masumoto J., Taniguchi S., Ayukawa K., Sarvotham H., Kishino T., Niikawa N., Hidaka E., Katsuyama T., Higuchi T., Sagara J.
      J. Biol. Chem. 274:33835-33838(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Leukemia.
    2. "TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers."
      Conway K.E., McConnell B.B., Bowring C.E., Donald C.D., Warren S.T., Vertino P.M.
      Cancer Res. 60:6236-6242(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
      Tissue: Fibroblast.
    3. "A splice variant of ASC regulates IL-1beta release and aggregates differently from intact ASC."
      Matsushita K., Takeoka M., Sagara J., Itano N., Kurose Y., Nakamura A., Taniguchi S.
      Mediators Inflamm. 2009:287387-287387(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 2), FUNCTION (ISOFORM 2), MASS SPECTROMETRY (ISOFORM 2).
    4. "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 (ISOFORM 1).
    5. "CARD5 protein is a CARD/PYRIN family member that is involved in apoptosis signal transduction."
      Bertin J.
      Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
    6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Colon mucosa.
    7. "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] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-195 (ISOFORM 1).
      Tissue: Lymph and Pancreas.
    8. "Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1."
      McConnell B.B., Vertino P.M.
      Cancer Res. 60:6243-6247(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    9. Cited for: INTERACTION WITH NLRC4.
    10. "Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis."
      Richards N., Schaner P., Diaz A., Stuckey J., Shelden E., Wadhwa A., Gumucio D.L.
      J. Biol. Chem. 276:39320-39329(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MEFV.
    11. "PYPAF1: a PYRIN-containing APAF1-like protein that assembles with ASC and activates NF-kB."
      Manji G.A., Wang L., Geddes B.J., Brown M., Merriam S., Al-Garawi A., Mak S., Lora J.M., Briskin M., Jurman M., Cao J., DiStefano P.S., Bertin J.
      J. Biol. Chem. 277:11570-11575(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NLRP3, DOMAIN.
    12. "The PYRIN-CARD protein ASC is an activating adaptor for caspase-1."
      Srinivasula S.M., Poyet J.L., Razmara M., Datta P., Zhang Z., Alnemri E.S.
      J. Biol. Chem. 277:21119-21122(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CASP1; NLRC4 AND CARD16.
    13. "The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor kappaB activation pathways."
      Stehlik C., Fiorentino L., Dorfleutner A., Bruey J.M., Ariza E.M., Sagara J., Reed J.C.
      J. Exp. Med. 196:1605-1615(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CHUK AND IKBKB.
    14. "The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta."
      Martinon F., Burns K., Tschopp J.
      Mol. Cell 10:417-426(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN NLPR1 INFLAMMASOME.
    15. Cited for: FUNCTION IN APOPTOSIS, INTERACTION WITH CASP8, MUTAGENESIS OF LEU-12.
    16. "The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation."
      Stehlik C., Krajewska M., Welsh K., Krajewski S., Godzik A., Reed J.C.
      Biochem. J. 373:101-113(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PYDC1, PHOSPHORYLATION.
    17. "Apoptosis-associated speck-like protein containing a caspase recruitment domain is a regulator of procaspase-1 activation."
      Stehlik C., Lee S.H., Dorfleutner A., Stassinopoulos A., Sagara J., Reed J.C.
      J. Immunol. 171:6154-6163(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CASP1 AND RIPK2.
    18. "NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder."
      Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N., Tschopp J.
      Immunity 20:319-325(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN NLRP2 AND NLRP3 INFLAMMASOMES, INTERACTION WITH NLRP2 AND NLRP3, SUBCELLULAR LOCATION.
    19. "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1."
      Wang Y., Hasegawa M., Imamura R., Kinoshita T., Kondo C., Konaka K., Suda T.
      Int. Immunol. 16:777-786(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NLRP10.
    20. "Cryopyrin-induced interleukin 1beta secretion in monocytic cells: enhanced activity of disease-associated mutants and requirement for ASC."
      Dowds T.A., Masumoto J., Zhu L., Inohara N., Nunez G.
      J. Biol. Chem. 279:21924-21928(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NLRP3.
    21. "PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages."
      Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C., Reed J.C.
      J. Biol. Chem. 279:51897-51907(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NLRP2, MUTAGENESIS OF GLU-13.
    22. "ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway."
      Ohtsuka T., Ryu H., Minamishima Y.A., Macip S., Sagara J., Nakayama K.I., Aaronson S.A., Lee S.W.
      Nat. Cell Biol. 6:121-128(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN APOPTOSIS, SUBCELLULAR LOCATION, INTERACTION WITH BAX.
    23. "Role of charged and hydrophobic residues in the oligomerization of the PYRIN domain of ASC."
      Moriya M., Taniguchi S., Wu P., Liepinsh E., Otting G., Sagara J.
      Biochemistry 44:575-583(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SELF-ASSOCIATION, MUTAGENESIS OF ILE-8; LEU-12; GLU-13; LEU-15; GLU-19; LEU-20; LYS-21; PHE-23; LEU-25; LYS-26; LEU-27; PRO-40; ARG-41; LEU-45; MET-47; ASP-48; LEU-52; LEU-56; GLU-62; GLU-67; LEU-68; VAL-72 AND MET-76.
    24. "Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization."
      Yu J.W., Wu J., Zhang Z., Datta P., Ibrahimi I., Taniguchi S., Sagara J., Fernandes-Alnemri T., Alnemri E.S.
      Cell Death Differ. 13:236-249(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION WITH INFLAMMASOMES.
    25. "ASC directs NF-kappaB activation by regulating receptor interacting protein-2 (RIP2) caspase-1 interactions."
      Sarkar A., Duncan M., Hart J., Hertlein E., Guttridge D.C., Wewers M.D.
      J. Immunol. 176:4979-4986(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CASP1.
    26. "ASC mediates the induction of multiple cytokines by Porphyromonas gingivalis via caspase-1-dependent and -independent pathways."
      Taxman D.J., Zhang J., Champagne C., Bergstralh D.T., Iocca H.A., Lich J.D., Ting J.P.
      J. Immunol. 177:4252-4256(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    27. "The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation."
      Fernandes-Alnemri T., Wu J., Yu J.W., Datta P., Miller B., Jankowski W., Rosenberg S., Zhang J., Alnemri E.S.
      Cell Death Differ. 14:1590-1604(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    28. "Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation."
      Faustin B., Lartigue L., Bruey J.-M., Luciano F., Sergienko E., Bailly-Maitre B., Volkmann N., Hanein D., Rouiller I., Reed J.C.
      Mol. Cell 25:713-724(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN NLRP1 INFLAMMASOME.
    29. "Mechanism of ASC-mediated apoptosis: bid-dependent apoptosis in type II cells."
      Hasegawa M., Kawase K., Inohara N., Imamura R., Yeh W.C., Kinoshita T., Suda T.
      Oncogene 26:1748-1756(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN APOPTOSIS.
    30. "Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation."
      Dorfleutner A., Bryan N.B., Talbott S.J., Funya K.N., Rellick S.L., Reed J.C., Shi X., Rojanasakul Y., Flynn D.C., Stehlik C.
      Infect. Immun. 75:1484-1492(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PYDC2.
    31. "Pyrin-only protein 2 modulates NF-kappaB and disrupts ASC:CLR interactions."
      Bedoya F., Sandler L.L., Harton J.A.
      J. Immunol. 178:3837-3845(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PYDC2.
    32. Cited for: INTERACTION WITH PYDC1, MUTAGENESIS OF GLU-13; TYR-36 AND ASP-48.
    33. "Activation of inflammasomes requires intracellular redistribution of the apoptotic speck-like protein containing a caspase recruitment domain."
      Bryan N.B., Dorfleutner A., Rojanasakul Y., Stehlik C.
      J. Immunol. 182:3173-3182(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    34. Cited for: FUNCTION.
    35. "AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA."
      Fernandes-Alnemri T., Yu J.W., Datta P., Wu J., Alnemri E.S.
      Nature 458:509-513(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN AIM2 INFLAMMASOME, INTERACTION WITH AIM2.
    36. "AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC."
      Hornung V., Ablasser A., Charrel-Dennis M., Bauernfeind F., Horvath G., Caffrey D.R., Latz E., Fitzgerald K.A.
      Nature 458:514-518(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN AIM2 INFLAMMASOME, INTERACTION WITH AIM2.
    37. "Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) regulates inflammasomes."
      Bryan N.B., Dorfleutner A., Kramer S.J., Yun C., Rojanasakul Y., Stehlik C.
      J. Inflamm. (Lond.) 7:23-23(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION (ISOFORMS 2 AND 3).
    38. "Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production."
      Poeck H., Bscheider M., Gross O., Finger K., Roth S., Rebsamen M., Hannesschlager N., Schlee M., Rothenfusser S., Barchet W., Kato H., Akira S., Inoue S., Endres S., Peschel C., Hartmann G., Hornung V., Ruland J.
      Nat. Immunol. 11:63-69(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DDX58.
    39. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    40. "IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection."
      Kerur N., Veettil M.V., Sharma-Walia N., Bottero V., Sadagopan S., Otageri P., Chandran B.
      Cell Host Microbe 9:363-375(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IFI16.
    41. "The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activated protein kinase (MAPK), and chemokine induction independent of the inflammasome."
      Taxman D.J., Holley-Guthrie E.A., Huang M.T., Moore C.B., Bergstralh D.T., Allen I.C., Lei Y., Gris D., Ting J.P.
      J. Biol. Chem. 286:19605-19616(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    42. "Central and overlapping role of cathepsin B and inflammasome adaptor ASC in antigen presenting function of human dendritic cells."
      Guo X., Dhodapkar K.M.
      Hum. Immunol. 73:871-878(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    43. "A role for mitochondria in NLRP3 inflammasome activation."
      Zhou R., Yazdi A.S., Menu P., Tschopp J.
      Nature 469:221-225(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    44. "The death-domain fold of the ASC PYRIN domain, presenting a basis for PYRIN/PYRIN recognition."
      Liepinsh E., Barbals R., Dahl E., Sharipo A., Staub E., Otting G.
      J. Mol. Biol. 332:1155-1163(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-91, FUNCTION OF DAPIN DOMAIN.
    45. "Structure and interdomain dynamics of apoptosis-associated speck-like protein containing a CARD (ASC)."
      de Alba E.
      J. Biol. Chem. 284:32932-32941(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR.

    Entry informationi

    Entry nameiASC_HUMAN
    AccessioniPrimary (citable) accession number: Q9ULZ3
    Secondary accession number(s): Q96D12
    , Q9BSZ5, Q9HBD0, Q9NXJ8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 18, 2001
    Last sequence update: March 1, 2001
    Last modified: October 1, 2014
    This is version 139 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    In breast tumorigenesis, methylation-mediated silencing may affect genes and proteins that act as positive mediators of cell death.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3