4uz0

Structural highlights

Disease

[NOL3_HUMAN] Familial cortical myoclonus. The disease is caused by mutations affecting the gene represented in this entry.

Function

[NOL3_HUMAN] Isoform 1: May be involved in RNA splicing.^[1] 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 (By similarity). Secondly by interacting with CASP8 in a mitochondria localization- and phosphorylation-dependent manner, limiting the amount of soluble CASP8 available for DISC-mediated activation (By similarity). 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 (PubMed:15004034). Inhibits calcium-mediated cell death by functionning as a cytosolic calcium buffer, dissociating its interaction with CASP8 and maintaining calcium homeostasis (PubMed:15509781). Negatively regulates oxidative stress-induced apoptosis by phosphorylation-dependent suppression of the mitochondria-mediated intrinsic pathway, by blocking CASP2 activation and BAX translocation (By similarity). Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome c from mitochondria in a caspase-independent manner (By similarity). Also inhibits TNF-induced necrosis by preventing TNF-signaling pathway through TNFRSF1A interaction abrogating the recruitment of RIPK1 to complex I (By similarity). Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation of proliferation, in response to hypoxia (By similarity). Inhibits too myoblast differentiation through caspase inhibition (By similarity).[UniProtKB:Q62881][UniProtKB:Q9D1X0]^{[2] [3]}

References

1. ↑ Stoss O, Schwaiger FW, Cooper TA, Stamm S. Alternative splicing determines the intracellular localization of the novel nuclear protein Nop30 and its interaction with the splicing factor SRp30c. J Biol Chem. 1999 Apr 16;274(16):10951-62. PMID:10196175
2. ↑ Gustafsson AB, Tsai JG, Logue SE, Crow MT, Gottlieb RA. Apoptosis repressor with caspase recruitment domain protects against cell death by interfering with Bax activation. J Biol Chem. 2004 May 14;279(20):21233-8. Epub 2004 Mar 5. PMID:15004034 doi:http://dx.doi.org/10.1074/jbc.M400695200
3. ↑ Jo DG, Jun JI, Chang JW, Hong YM, Song S, Cho DH, Shim SM, Lee HJ, Cho C, Kim DH, Jung YK. Calcium binding of ARC mediates regulation of caspase 8 and cell death. Mol Cell Biol. 2004 Nov;24(22):9763-70. PMID:15509781 doi:http://dx.doi.org/10.1128/MCB.24.22.9763-9770.2004
4. ↑ Jang TH, Kim SH, Jeong JH, Kim S, Kim YG, Park HH. Crystal structure of caspase recruiting domain (CARD) of apoptosis repressor with CARD (ARC) and its implication in inhibition of apoptosis. Sci Rep. 2015 Jun 3;5:9847. doi: 10.1038/srep09847. PMID:26038885 doi:http://dx.doi.org/10.1038/srep09847