| Post Translational Modifications | Phosphorylation at Thr-149 is required for its antiapoptotic effect by blocking death-inducing signaling complex death-inducing signaling complex (DISC) activity through the control of interaction with CASP8. Phosphorylation at Thr-149 results in translocation to mitochondria and this translocation enables the binding to CASP8. Dephosphorylated at Thr-149 by calcineurin.doesn't inhibit the association between FADD and CASP8 and the consequent apoptosis. Polyubiquitinated by MDM2.promoting proteasomal-dependent degradation in response to apoptotic stimuli. |
| Function | Isoform 1: May be involved in RNA splicing. Isoform 2: Functions as an apoptosis repressor that blocks multiple modes of cell death. Inhibits extrinsic apoptotic pathways through two different ways. Firstly by interacting with FAS and FADD upon FAS activation blocking death-inducing signaling complex (DISC) assembly. Secondly by interacting with CASP8 in a mitochondria localization- and phosphorylation-dependent manner, limiting the amount of soluble CASP8 available for DISC-mediated activation. Inhibits intrinsic apoptotic pathway in response to a wide range of stresses, through its interaction with BAX resulting in BAX inactivation, preventing mitochondrial dysfunction and release of pro-apoptotic factors. Inhibits calcium-mediated cell death by functioning as a cytosolic calcium buffer, dissociating its interaction with CASP8 and maintaining calcium homeostasis. Negatively regulates oxidative stress-induced apoptosis by phosphorylation-dependent suppression of the mitochondria-mediated intrinsic pathway, by blocking CASP2 activation and BAX translocation. Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome c from mitochondria in a caspase-independent manner. Also inhibits TNF-induced necrosis by preventing TNF-signaling pathway through TNFRSF1A interaction abrogating the recruitment of RIPK1 to complex I. Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation of proliferation, in response to hypoxia. Inhibits too myoblast differentiation through caspase inhibition. |
| Protein Name | Nucleolar Protein 3Apoptosis Repressor With CardMuscle-Enriched Cytoplasmic ProteinMypNucleolar Protein Of 30 KdaNop30 |
| Cellular Localisation | Isoform 1: NucleusNucleolusThe Sr-Rich C-Terminus Mediates Nuclear LocalizationIsoform 3: CytoplasmIsoform 2: CytoplasmMitochondrionSarcoplasmic ReticulumMembraneLipid-AnchorPhosphorylation At Thr-149 Results In Translocation To MitochondriaColocalized With Mitochondria In Response To Oxidative Stress |
| Alternative Protein Names | Nucleolar Protein 3 proteinApoptosis Repressor With Card proteinMuscle-Enriched Cytoplasmic Protein proteinMyp proteinNucleolar Protein Of 30 Kda proteinNop30 proteinNOL3 proteinARC proteinNOP protein |
Information sourced from Uniprot.org
