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Q9ULZ3 (ASC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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=hASC
Alternative name(s):
Caspase recruitment domain-containing protein 5
PYD and CARD domain-containing protein
Target of methylation-induced silencing 1
Gene names
Name:PYCARD
Synonyms:ASC, CARD5, TMS1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length195 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. 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. Ref.3 Ref.8 Ref.13 Ref.15 Ref.18 Ref.22 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.41 Ref.42 Ref.44

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. 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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.25 Ref.27 Ref.30 Ref.31 Ref.32 Ref.35 Ref.36 Ref.38 Ref.40

Subcellular location

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. Ref.8 Ref.18 Ref.22 Ref.33 Ref.43

Tissue specificity

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.

Domain

The DAPIN domain mediates homotypic interactions with DAPIN domains of proteins such as of NLRP3, PYDC1 and AIM2 (Ref.11, Ref.16, Ref.35 and Ref.36). Ref.11 Ref.44

The CARD domain mediates interaction with CASP1 and NLRC4 (Ref.17 and Ref.12). Ref.11 Ref.44

Post-translational modification

Phosphorylated. Ref.16

Miscellaneous

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

Sequence similarities

Contains 1 CARD domain.

Contains 1 DAPIN domain.

Sequence caution

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

Ontologies

Keywords
   Biological processApoptosis
Immunity
Inflammatory response
Innate immunity
   Cellular componentCytoplasm
Endoplasmic reticulum
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseTumor suppressor
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Non-traceable author statement PubMed 12019269. Source: UniProtKB

activation of innate immune response

Inferred from direct assay Ref.40. Source: UniProtKB

apoptotic process

Traceable author statement Ref.1. Source: ProtInc

cellular response to interleukin-1

Inferred from direct assay Ref.13. Source: UniProtKB

cellular response to lipopolysaccharide

Inferred from direct assay Ref.13. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from direct assay Ref.13. Source: UniProtKB

defense response to Gram-negative bacterium

Inferred from mutant phenotype Ref.26Ref.41. Source: UniProtKB

defense response to virus

Inferred from direct assay Ref.40. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

interleukin-1 beta production

Inferred from electronic annotation. Source: Ensembl

intrinsic apoptotic signaling pathway by p53 class mediator

Inferred from mutant phenotype Ref.22. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from mutant phenotype Ref.22. Source: UniProtKB

macropinocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

myeloid dendritic cell activation

Inferred from mutant phenotype Ref.42. Source: UniProtKB

myeloid dendritic cell activation involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay Ref.13. Source: UniProtKB

negative regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.25. Source: UniProtKB

negative regulation of interferon-beta production

Inferred from mutant phenotype Ref.36. Source: UniProtKB

negative regulation of protein serine/threonine kinase activity

Inferred from direct assay Ref.13. Source: UniProtKB

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype Ref.41. Source: UniProtKB

positive regulation of JNK cascade

Inferred from mutant phenotype Ref.41. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of T cell activation

Inferred from mutant phenotype Ref.42. Source: UniProtKB

positive regulation of T cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of actin filament polymerization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of activated T cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of adaptive immune response

Inferred from mutant phenotype Ref.42. Source: UniProtKB

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

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of chemokine secretion

Inferred from mutant phenotype Ref.41. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity

Inferred from direct assay Ref.35. Source: UniProtKB

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

Inferred from direct assay Ref.18. Source: HGNC

positive regulation of defense response to virus by host

Inferred from electronic annotation. Source: Ensembl

positive regulation of extrinsic apoptotic signaling pathway

Inferred from direct assay Ref.29. Source: UniProtKB

positive regulation of interferon-gamma production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-1 beta secretion

Inferred from direct assay Ref.18. Source: HGNC

positive regulation of interleukin-10 secretion

Inferred from mutant phenotype Ref.26. Source: UniProtKB

positive regulation of interleukin-6 production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-6 secretion

Inferred from mutant phenotype Ref.26. Source: UniProtKB

positive regulation of interleukin-8 secretion

Inferred from mutant phenotype Ref.26. Source: UniProtKB

positive regulation of phagocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of release of cytochrome c from mitochondria

Inferred from direct assay Ref.22. Source: UniProtKB

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.34. Source: UniProtKB

positive regulation of tumor necrosis factor production

Inferred from mutant phenotype Ref.26Ref.41. Source: UniProtKB

regulation of Rac GTPase activity

Inferred from electronic annotation. Source: Ensembl

regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

regulation of intrinsic apoptotic signaling pathway

Inferred from direct assay Ref.22. Source: UniProtKB

regulation of protein stability

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of tumor necrosis factor-mediated signaling pathway

Inferred from mutant phenotype Ref.22. Source: UniProtKB

signal transduction

Non-traceable author statement PubMed 12019269. Source: UniProtKB

tumor necrosis factor-mediated signaling pathway

Inferred from direct assay Ref.16. Source: HGNC

   Cellular_componentAIM2 inflammasome complex

Inferred from direct assay Ref.35. Source: UniProtKB

IkappaB kinase complex

Traceable author statement Ref.16. Source: HGNC

NLRP1 inflammasome complex

Inferred from direct assay Ref.14. Source: UniProtKB

NLRP3 inflammasome complex

Inferred from direct assay Ref.18. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.22. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular region

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from direct assay Ref.22. Source: UniProtKB

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from direct assay. Source: HPA

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionPyrin domain binding

Inferred from physical interaction Ref.18. Source: HGNC

cysteine-type endopeptidase activator activity involved in apoptotic process

Non-traceable author statement PubMed 12019269. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12019269. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.18. Source: HGNC

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9ULZ3-1)

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.
Isoform 2 (identifier: Q9ULZ3-2)

Also known as: Asc-b; vASC;

The sequence of this isoform differs from the canonical sequence as follows:
     93-111: Missing.
Isoform 3 (identifier: Q9ULZ3-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 195195Apoptosis-associated speck-like protein containing a CARD
PRO_0000064692

Regions

Domain1 – 9191DAPIN
Domain107 – 19589CARD

Natural variations

Alternative sequence26 – 8560Missing in isoform 3.
VSP_004118
Alternative sequence93 – 11119Missing in isoform 2.
VSP_004119

Experimental info

Mutagenesis81I → A: Abolishes homooligomerization. Ref.23
Mutagenesis121L → A: Abolishes homooligomerization. Ref.15 Ref.23
Mutagenesis121L → Q: Abolishes promotion of apoptosis and NF-kappa-B activation. Ref.15 Ref.23
Mutagenesis131E → A: Abolishes interaction with PYDC1. Ref.21 Ref.23 Ref.32
Mutagenesis131E → W: Abolishes interaction with NLRP2. Ref.21 Ref.23 Ref.32
Mutagenesis151L → A: Abolishes homooligomerization. Ref.23
Mutagenesis191E → A: Abolishes homooligomerization. Ref.23
Mutagenesis201L → A: Abolishes homooligomerization. Ref.23
Mutagenesis211K → A, E or Q: Abolishes homooligomerization. Ref.23
Mutagenesis231F → A: Abolishes homooligomerization. Ref.23
Mutagenesis251L → A, E, G, K, N or Q: Abolishes homooligomerization. Ref.23
Mutagenesis261K → A or Q: Abolishes homooligomerization. Ref.23
Mutagenesis271L → A: Abolishes homooligomerization. Ref.23
Mutagenesis361Y → A: Abolishes interaction with PYDC1. Ref.32
Mutagenesis401P → A: Abolishes homooligomerization. Ref.23
Mutagenesis411R → A, Q or W: Abolishes homooligomerization. Ref.23
Mutagenesis451L → A: Abolishes homooligomerization. Ref.23
Mutagenesis471M → A, N or Q: Abolishes homooligomerization. Ref.23
Mutagenesis481D → A or K: Abolishes homooligomerization. Ref.23 Ref.32
Mutagenesis481D → A: Abolishes interaction with PYDC1. Ref.23 Ref.32
Mutagenesis521L → A: Abolishes homooligomerization. Ref.23
Mutagenesis561L → A: Abolishes homooligomerization. Ref.23
Mutagenesis621E → A: Abolishes homooligomerization. Ref.23
Mutagenesis671E → A: Abolishes homooligomerization. Ref.23
Mutagenesis681L → A: Abolishes homooligomerization. Ref.23
Mutagenesis721V → A: Abolishes homooligomerization. Ref.23
Mutagenesis761M → A: Abolishes homooligomerization. Ref.23

Secondary structure

............................... 195
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (fASC) [UniParc].

Last modified March 1, 2001. Version 2.
Checksum: 455987286586F46A

FASTA19521,627
        10         20         30         40         50         60 
MGRARDAILD ALENLTAEEL KKFKLKLLSV PLREGYGRIP RGALLSMDAL DLTDKLVSFY 

        70         80         90        100        110        120 
LETYGAELTA NVLRDMGLQE MAGQLQAATH QGSGAAPAGI QAPPQSAAKP GLHFIDQHRA 

       130        140        150        160        170        180 
ALIARVTNVE WLLDALYGKV LTDEQYQAVR AEPTNPSKMR KLFSFTPAWN WTCKDLLLQA 

       190 
LRESQSYLVE DLERS 

« Hide

Isoform 2 (Asc-b) (vASC) [UniParc].

Checksum: C4AB645696FA115D
Show »

FASTA17619,969
Isoform 3 (Asc-c) [UniParc].

Checksum: F46DB2DF379E95E9
Show »

FASTA13515,030

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis."
Geddes B.J., Wang L., Huang W.-J., Lavellee M., Manji G.A., Brown M., Jurman M., Cao J., Morgenstern J., Merriam S., Glucksmann M.A., DiStefano P.S., Bertin J.
Biochem. Biophys. Res. Commun. 284:77-82(2001) [PubMed] [Europe PMC] [Abstract]
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]"ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis."
Masumoto J., Dowds T.A., Schaner P., Chen F.F., Ogura Y., Li M., Zhu L., Katsuyama T., Sagara J., Taniguchi S., Gumucio D.L., Nunez G., Inohara N.
Biochem. Biophys. Res. Commun. 303:69-73(2003) [PubMed] [Europe PMC] [Abstract]
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]"Mapping of POP1-binding site on pyrin domain of ASC."
Srimathi T., Robbins S.L., Dubas R.L., Chang H., Cheng H., Roder H., Park Y.C.
J. Biol. Chem. 283:15390-15398(2008) [PubMed] [Europe PMC] [Abstract]
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]"Mechanism and repertoire of ASC-mediated gene expression."
Hasegawa M., Imamura R., Motani K., Nishiuchi T., Matsumoto N., Kinoshita T., Suda T.
J. Immunol. 182:7655-7662(2009) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10708.1. [Q9ULZ3-1]
CCDS10709.1. [Q9ULZ3-2]
RefSeqNP_037390.2. NM_013258.4. [Q9ULZ3-1]
NP_660183.1. NM_145182.2. [Q9ULZ3-2]
UniGeneHs.499094.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ9ULZ3.
SMRQ9ULZ3. Positions 1-195.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118876. 11 interactions.
DIPDIP-27618N.
IntActQ9ULZ3. 21 interactions.
MINTMINT-206960.
STRING9606.ENSP00000247470.

PTM databases

PhosphoSiteQ9ULZ3.

Polymorphism databases

DMDM18203507.

Proteomic databases

MaxQBQ9ULZ3.
PaxDbQ9ULZ3.
PRIDEQ9ULZ3.

Protocols and materials databases

DNASU29108.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000247470; ENSP00000247470; ENSG00000103490. [Q9ULZ3-1]
ENST00000350605; ENSP00000340441; ENSG00000103490. [Q9ULZ3-2]
GeneID29108.
KEGGhsa:29108.
UCSCuc002ebm.3. human. [Q9ULZ3-2]
uc010cak.3. human. [Q9ULZ3-1]

Organism-specific databases

CTD29108.
GeneCardsGC16M031212.
H-InvDBHIX0012985.
HGNCHGNC:16608. PYCARD.
HPACAB006853.
CAB015948.
HPA049074.
MIM606838. gene.
neXtProtNX_Q9ULZ3.
PharmGKBPA134950175.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39139.
HOGENOMHOG000034090.
HOVERGENHBG018739.
InParanoidQ9ULZ3.
KOK12799.
OMAPMDAVDL.
OrthoDBEOG786H4P.
PhylomeDBQ9ULZ3.
TreeFamTF337882.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ9ULZ3.
BgeeQ9ULZ3.
CleanExHS_PYCARD.
GenevestigatorQ9ULZ3.

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

ChiTaRSPYCARD. human.
EvolutionaryTraceQ9ULZ3.
GeneWikiPYCARD.
GenomeRNAi29108.
NextBio52169.
PROQ9ULZ3.
SOURCESearch...

Entry information

Entry nameASC_HUMAN
AccessionPrimary (citable) accession number: Q9ULZ3
Secondary accession number(s): Q96D12 expand/collapse secondary AC list , Q9BSZ5, Q9HBD0, Q9NXJ8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM