Protein: Arginine ADP-riboxanase OspC3 (A0A0H2US87)
Organism: Shigella flexneri
Function: ADP-riboxanase effector that inhibits host cell pyroptosis. Acts by mediating arginine ADP-riboxanation of host CASP4/CASP11, blocking CASP4/CASP11 autoprocessing. This prevents CASP4 activation and ability to recognize and cleave GSDMD, thereby inhibiting LPS-induced pyroptosis. ADP-riboxanation takes place in two steps: OspC3 first catalyzes ADP- ribosylation of target Arg, and then initiates a deamination to remove one N-omega group. Independently of its ADP- riboxanase activity, acts as an inhibitor of calcium signaling by inhibiting host calmodulin, preventing activation of the JAK-STAT signaling pathway in response to interferon-beta. Mechanistically, acts by binding to the apo form of calmodulin, preventing calcium-binding and ability to activate host CaMK2 (CAMKII), which is required to stimulate the JAK-STAT signaling pathway in response to interferon-beta
Subcellular location: Secreted. Host cytoplasm. Note=Secreted via the type III secretion system (T3SS)
Sequence: MKIPEAVNHINVQNNIDLVDGKINPNKDTKALQKNISCVTNSSSSGISEKHLDHCADTVKSFLRKSIAAQSYSKMFSQGTSFKSLNLSIEAPSGARSSFRSLEHLDKVSRHYLSEIIQKTHPLSSDERHLLSIIINSDFNFRHQSNANLSNNTLNIKSFDKIKSENIQTYKNTFSEDIEEIANHDFVFFGVEISNHQETLPLNKTHHTVDFGANAYIIDHDSPYGYMTLTDHFDNAIPPVFYHEHQSFFLDNFKEVVDEVSRYVHGNQGKTDVPIFNTKDMRLGIGLHLIDFIRKSKDQRFREFCYNKNIDPVSLDRIINFVFQLEYHIPRMLSTDNFKKIKLRDISLEDAIKASNYEEINNKVTDKKMAHQALAYSLGNKKADIALYLLSKFNFTKQDVAEMEKMKNNRYCNLYDVEYLLSKDGANYKVLEYFINNGLVDVNKKFQKVNSGDTMLDNAMKSKDSKMIDFLLKNGAILGKRFEI
InterPro domains: - IPR010366: Arginine ADP-riboxanase OspC1-4 (family) [191-482]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0016829 (lyase activity), GO:0016840 (carbon-nitrogen lyase activity), GO:0005516 (calmodulin binding), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0016841 (ammonia-lyase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0009605 (response to external stimulus), GO:0044068 (modulation by symbiont of host cellular process), GO:0009607 (response to biotic stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0023051 (regulation of signaling), GO:0035821 (modulation of process of another organism), GO:0044403 (biological process involved in symbiotic interaction), GO:0051707 (response to other organism), GO:0052027 (modulation by symbiont of host signal transduction pathway), GO:0044501 (modulation of signal transduction in another organism), GO:0051701 (biological process involved in interaction with host), GO:0052040 (modulation by symbiont of host programmed cell death), GO:0043207 (response to external biotic stimulus), GO:0052173 (response to defenses of other organism), GO:0010646 (regulation of cell communication), GO:0044003 (modulation by symbiont of host process), GO:0009966 (regulation of signal transduction), GO:0075136 (response to host), GO:0052200 (response to host defenses), GO:0052041 (suppression by symbiont of host programmed cell death), GO:0052029 (suppression by symbiont of host signal transduction pathway), GO:0052031 (modulation by symbiont of host defense response), GO:1902531 (regulation of intracellular signal transduction), GO:0050848 (regulation of calcium-mediated signaling)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005576 (extracellular region)