DegronMD - Q15233(NONO)

FUNCTION: DNA- and RNA binding protein, involved in several nuclear processes (PubMed:11525732, PubMed:12403470, PubMed:26571461). Binds the conventional octamer sequence in double-stranded DNA (PubMed:11525732, PubMed:12403470, PubMed:26571461). Also binds single-stranded DNA and RNA at a site independent of the duplex site (PubMed:11525732, PubMed:12403470, PubMed:26571461). Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ (PubMed:11525732, PubMed:12403470, PubMed:26571461). Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b (PubMed:12403470). Together with PSPC1, required for the formation of nuclear paraspeckles (PubMed:22416126). The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs (PubMed:11525732). The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1 (PubMed:10858305). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends (PubMed:15590677). In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex (PubMed:15590677). NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity (PubMed:11897684). NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription (By similarity). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer (By similarity). Important for the functional organization of GABAergic synapses (By similarity). Plays a specific and important role in the regulation of synaptic RNAs and GPHN/gephyrin scaffold structure, through the regulation of GABRA2 transcript (By similarity). Plays a key role during neuronal differentiation by recruiting TET1 to genomic loci and thereby regulating 5-hydroxymethylcytosine levels (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728, PubMed:30270045). Promotes activation of the cGAS-STING pathway in response to HIV-2 infection: acts by interacting with HIV-2 Capsid protein p24, thereby promoting detection of viral DNA by CGAS, leading to CGAS-mediated inmmune activation (PubMed:30270045). In contrast, the weak interaction with HIV-1 Capsid protein p24 does not allow activation of the cGAS-STING pathway (PubMed:30270045). {ECO:0000250|UniProtKB:Q99K48, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:12403470, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:26571461, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:30270045}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.T431P	TCGA-AX-A2HD	UCEC	TCGA	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation altering degron motif	0.7031
p.T431P	DO42608	UCEC	ICGC	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation altering degron motif	0.7031
p.G423R	TCGA-GN-A262	SKCM	TCGA	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.2778
p.G423R	DO37515	SKCM	ICGC	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.2778
p.P429T	TCGA-MX-A5UJ	STAD	TCGA	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation altering degron motif	0.7031
p.P429T	DO48547	STAD	ICGC	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation altering degron motif	0.7031
p.M420I	DO229025	LICA	ICGC	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.1944
p.A439S	DO229036	LICA	ICGC	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.1389
p.D422Y	SIDM00841	Colorectal Carcinoma	GDSC	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.25
p.D422Y	ACH-000651	Colon/Colorectal Cancer	CCLE	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.25
p.D422Y	SW620	large intestine	COSMIC	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.25
p.D422G	SIDM00217	Colorectal Carcinoma	GDSC	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.25
p.D422G	ACH-000999	Colon/Colorectal Cancer	CCLE	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.25
p.D422G	SNU-1040	large intestine	COSMIC	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.25
p.M420K	ACH-001853	Bile Duct Cancer	CCLE	LGLTPPTT	DEG_SCF_FBW7_1	425:432	Mutation rewiring degron network	0.1944

DegronMD: protein-targeted degradation, mutation and drug response to degrons

NONO

UniProt ID: Q15233

Entrez ID: 4841

Protein name: Non-POU domain-containing octamer-binding protein (NonO protein) (54 kDa nuclear RNA- and DNA-binding protein) (p54(nrb)) (p54nrb) (55 kDa nuclear protein) (NMT55) (DNA-binding p52/p100 complex, 52 kDa subunit)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for NONO in