DegronMD - P26651(ZFP36)

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:9703499, PubMed:10330172, PubMed:10751406, PubMed:11279239, PubMed:12115244, PubMed:12748283, PubMed:15187101, PubMed:15634918, PubMed:17030620, PubMed:16702957, PubMed:20702587, PubMed:20221403, PubMed:21775632, PubMed:27193233, PubMed:23644599, PubMed:25815583, PubMed:31439631). Acts as an 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:15687258, PubMed:23644599). Recruits deadenylase CNOT7 (and probably the CCR4-NOT complex) via association with CNOT1, and hence promotes ARE-mediated mRNA deadenylation (PubMed:23644599). Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs (PubMed:11719186, PubMed:12748283, PubMed:15687258, PubMed:16364915). Self regulates by destabilizing its own mRNA (PubMed:15187101). Binds to 3'-UTR ARE of numerous mRNAs and of its own mRNA (PubMed:10330172, PubMed:10751406, PubMed:12115244, PubMed:15187101, PubMed:15634918, PubMed:17030620, PubMed:16702957, PubMed:19188452, PubMed:20702587, PubMed:20221403, PubMed:21775632, PubMed:25815583). Plays a role in anti-inflammatory responses; suppresses tumor necrosis factor (TNF)-alpha production by stimulating ARE-mediated TNF-alpha mRNA decay and several other inflammatory ARE-containing mRNAs in interferon (IFN)- and/or lipopolysaccharide (LPS)-induced macrophages (By similarity). Plays also a role in the regulation of dendritic cell maturation at the post-transcriptional level, and hence operates as part of a negative feedback loop to limit the inflammatory response (PubMed:18367721). Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia (PubMed:21775632). Positively regulates early adipogenesis of preadipocytes by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (By similarity). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA (PubMed:20702587). Plays a role in maintaining skeletal muscle satellite cell quiescence by promoting ARE-mediated mRNA decay of the myogenic determination factor MYOD1 mRNA (By similarity). Associates also with and regulates the expression of non-ARE-containing target mRNAs at the post-transcriptional level, such as MHC class I mRNAs (PubMed:18367721). Participates in association with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA) targeting ARE-containing mRNAs (PubMed:15766526). May also play a role in the regulation of cytoplasmic mRNA decapping; enhances decapping of ARE-containing RNAs, in vitro (PubMed:16364915). Involved in the delivery of target ARE-mRNAs to processing bodies (PBs) (PubMed:17369404). In addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA processing (By similarity). Negatively regulates nuclear poly(A)-binding protein PABPN1-stimulated polyadenylation activity on ARE-containing pre-mRNA during LPS-stimulated macrophages (By similarity). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (By similarity). Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis (PubMed:27182009). Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells (PubMed:26926077). {ECO:0000250|UniProtKB:P22893, ECO:0000269|PubMed:10330172, ECO:0000269|PubMed:10751406, ECO:0000269|PubMed:11279239, ECO:0000269|PubMed:11719186, ECO:0000269|PubMed:12115244, ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15187101, ECO:0000269|PubMed:15634918, ECO:0000269|PubMed:15687258, ECO:0000269|PubMed:15766526, ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:16702957, ECO:0000269|PubMed:17030620, ECO:0000269|PubMed:17369404, ECO:0000269|PubMed:18367721, ECO:0000269|PubMed:19188452, ECO:0000269|PubMed:20221403, ECO:0000269|PubMed:20702587, ECO:0000269|PubMed:21775632, ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:26926077, ECO:0000269|PubMed:27182009, ECO:0000269|PubMed:27193233, ECO:0000269|PubMed:31439631, ECO:0000269|PubMed:9703499}.; FUNCTION: (Microbial infection) Negatively regulates HTLV-1 TAX-dependent transactivation of viral long terminal repeat (LTR) promoter. {ECO:0000269|PubMed:14679154}. View more >>

GO - Biological processes (BP): 3'-UTR-mediated mRNA destabilization [GO:0061158]; 3'-UTR-mediated mRNA stabilization [GO:0070935]; cellular response to epidermal growth factor stimulus [GO:0071364]; cellular response to fibroblast growth factor stimulus [GO:0044344]; cellular response to glucocorticoid stimulus [GO:0071385]; cellular response to granulocyte macrophage colony-stimulating factor stimulus [GO:0097011]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to tumor necrosis factor [GO:0071356]; MAPK cascade [GO:0000165]; miRNA-mediated gene silencing by inhibition of translation [GO:0035278]; mRNA catabolic process [GO:0006402]; mRNA transport [GO:0051028]; negative regulation of erythrocyte differentiation [GO:0045647]; negative regulation of inflammatory response [GO:0050728]; negative regulation of interleukin-2 production [GO:0032703]; negative regulation of polynucleotide adenylyltransferase activity [GO:1904246]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of viral transcription [GO:0032897]; nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay [GO:0000288]; nuclear-transcribed mRNA catabolic process, deadenylation-independent decay [GO:0031086]; nuclear-transcribed mRNA poly(A) tail shortening [GO:0000289]; p38MAPK cascade [GO:0038066]; positive regulation of deadenylation-independent decapping of nuclear-transcribed mRNA [GO:1901835]; positive regulation of fat cell differentiation [GO:0045600]; positive regulation of gene silencing by miRNA [GO:2000637]; positive regulation of intracellular mRNA localization [GO:1904582]; positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay [GO:1900153]; positive regulation of nuclear-transcribed mRNA poly(A) tail shortening [GO:0060213]; regulation of keratinocyte apoptotic process [GO:1902172]; regulation of keratinocyte differentiation [GO:0045616]; regulation of keratinocyte proliferation [GO:0010837]; regulation of mRNA stability [GO:0043488]; regulation of tumor necrosis factor production [GO:0032680]; response to starvation [GO:0042594]; response to wounding [GO:0009611] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Open in full screen with detailed sequence annotations

Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A102S	TCGA-34-2609	LUSC	TCGA	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.2778
p.S108L	TCGA-MN-A4N1	LUAD	TCGA	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.1111
p.S108L	DO45328	LUAD	ICGC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.1111
p.P87L	DO11854	GBM	ICGC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.0833
p.E92G	DO16999	KIRC	ICGC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation blocking phosphorylation signal	0.6667
p.A96S	DO26981	LUSC	ICGC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation altering degron motif	0.7588
p.S108W	SIDM01048	Plasma Cell Myeloma	GDSC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.1111
p.S108W	ACH-000821	Myeloma	CCLE	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.1111
p.S108W	EJM	haematopoietic and lymphoid tissue	COSMIC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.1111
p.P95S	SIDM00222	Mesothelioma	GDSC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation blocking phosphorylation signal	0.75
p.P95S	ACH-000319	Lung Cancer	CCLE	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation blocking phosphorylation signal	0.75
p.P95S	MPP-89	pleura	COSMIC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation blocking phosphorylation signal	0.75
p.A86D	SIDM01011	B-Cell Non-Hodgkin's Lymphoma	GDSC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.0556
p.A86D	ACH-002254	Lymphoma	CCLE	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.0556
p.A86D	KARPAS-1106P	haematopoietic and lymphoid tissue	COSMIC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.0556
p.E92Q	SIDM00479	Esophageal Carcinoma	GDSC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation blocking phosphorylation signal	0.6667
p.E92Q	ACH-000679	Esophageal Cancer	CCLE	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation blocking phosphorylation signal	0.6667
p.E92Q	OE19	oesophagus	COSMIC	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation blocking phosphorylation signal	0.6667
p.L89P	ACH-001377	Pancreatic Cancer	CCLE	ATSTT	DEG_SPOP_SBC_1	96:100	Mutation rewiring degron network	0.1389

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

ZFP36

UniProt ID: P26651

Entrez ID: 7538

Protein name: mRNA decay activator protein ZFP36 (G0/G1 switch regulatory protein 24) (Growth factor-inducible nuclear protein NUP475) (Tristetraprolin) (Zinc finger protein 36) (Zfp-36)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for ZFP36 in