ASC_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: ASC_MOUSE
• UniProt AC: Q9EPB4
• Protein Name: Apoptosis-associated speck-like protein containing a CARD
• Gene Name: Pycard
• Organism: Mus musculus (Mouse).
• Sequence Length: 193
• Subcellular Localization: Cytoplasm . Endoplasmic reticulum. Mitochondrion. Nucleus. 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 acti
• Protein Description: 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 pyrin 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. Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA. [PubMed: 28314590]
• Protein Sequence: MGRARDAILDALENLSGDELKKFKMKLLTVQLREGYGRIPRGALLQMDAIDLTDKLVSYYLESYGLELTMTVLRDMGLQELAEQLQTTKEESGAVAAAASVPAQSTARTGHFVDQHRQALIARVTEVDGVLDALHGSVLTEGQYQAVRAETTSQDKMRKLFSFVPSWNLTCKDSLLQALKEIHPYLVMDLEQS

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
16	Phosphorylation	LDALENLSGDELKKF HHHHHHCCHHHHHHH	56.64	25777480
21	Acetylation	NLSGDELKKFKMKLL HCCHHHHHHHHHHHH	54.86	22733758
105	Phosphorylation	AASVPAQSTARTGHF HHHCCCCCCCCCCCC	26.58	28059163
144	Phosphorylation	SVLTEGQYQAVRAET CCCCCCHHHHHHEEC	14.86	-
180	Ubiquitination	DSLLQALKEIHPYLV HHHHHHHHHHCCHHH	58.60	-
193	Phosphorylation	LVMDLEQS------- HHHHCCCC-------	32.58	25521595

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
144	Y	Phosphorylation	Kinase	SYK	P43405	PSP
144	Y	Phosphorylation	Kinase	SYK	P48025	PSP
144	Y	Phosphorylation	Kinase	JNK1	Q91Y86	PSP

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of ASC_MOUSE !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of ASC_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ASC_MOUSE	Pycard	physical	24407287
ASC_MOUSE	Pycard	physical	25847972

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.