DegronMD - P47974(ZFP36L2)

FUNCTION: Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:25106868, PubMed:14981510). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:25106868). Functions by recruiting the CCR4-NOT deadenylase complex and probably other components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes (PubMed:25106868). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:20506496, PubMed:25106868, PubMed:14981510). Promotes ARE-containing mRNA decay of the low-density lipoprotein (LDL) receptor (LDLR) mRNA in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner (PubMed:25106868). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). Plays a role in mature peripheral neuron integrity by promoting ARE-containing mRNA decay of the transcriptional repressor REST mRNA. Plays a role in ovulation and oocyte meiotic maturation by promoting ARE-mediated mRNA decay of the luteinizing hormone receptor LHCGR mRNA. Acts as a negative regulator of erythroid cell differentiation: promotes glucocorticoid-induced self-renewal of erythroid cells by binding mRNAs that are induced or highly expressed during terminal erythroid differentiation and promotes their degradation, preventing erythroid cell differentiation. In association with ZFP36L1 maintains quiescence on developing B lymphocytes by promoting ARE-mediated decay of several mRNAs encoding cell cycle regulators that help B cells progress through the cell cycle, and hence ensuring accurate variable-diversity-joining (VDJ) recombination process and functional immune cell formation. Together with ZFP36L1 is also necessary for thymocyte development and prevention of T-cell acute lymphoblastic leukemia (T-ALL) transformation by promoting ARE-mediated mRNA decay of the oncogenic transcription factor NOTCH1 mRNA. {ECO:0000250|UniProtKB:P23949, ECO:0000269|PubMed:14981510, ECO:0000269|PubMed:20506496, ECO:0000269|PubMed:25106868}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.E126Q	TCGA-BH-A0W7	BRCA	TCGA	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation rewiring degron network	0.1111
p.E126Q	DO1272	BRCA	ICGC	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation rewiring degron network	0.1111
p.S123W	TCGA-E2-A10C	BRCA	TCGA	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation blocking phosphorylation signal	0.6389
p.S123W	DO1334	BRCA	ICGC	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation blocking phosphorylation signal	0.6389
p.R120L	TCGA-EE-A2MD	SKCM	TCGA	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation rewiring degron network	0.2778
p.R120L	DO37851	SKCM	ICGC	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation rewiring degron network	0.2778
p.S123L	TCGA-YC-A89H	BLCA	TCGA	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation blocking phosphorylation signal	0.6389
p.S123L	DO51948	BLCA	ICGC	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation blocking phosphorylation signal	0.6389
p.S105L	DO223030	ESCA	ICGC	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation rewiring degron network	0.0833
p.P104L	DO233944	GACA	ICGC	NKENK	DEG_APCC_KENBOX_2	114:118	Mutation rewiring degron network	0.0556

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

ZFP36L2

UniProt ID: P47974

Entrez ID: 678

Protein name: mRNA decay activator protein ZFP36L2 (Butyrate response factor 2) (EGF-response factor 2) (ERF-2) (TPA-induced sequence 11d) (Zinc finger protein 36, C3H1 type-like 2) (ZFP36-like 2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for ZFP36L2 in