DegronMD - Q7Z739(YTHDF3)

FUNCTION: Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:28106072, PubMed:28106076, PubMed:28281539, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:28106072, PubMed:28281539, PubMed:32492408). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex or PAN3 (PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:28106076, PubMed:32492408). Acts as a negative regulator of type I interferon response by down-regulating interferon-stimulated genes (ISGs) expression: acts by binding to FOXO3 mRNAs (By similarity). Binds to FOXO3 mRNAs independently of METTL3-mediated m6A modification (By similarity). Can also act as a regulator of mRNA stability in cooperation with YTHDF2 by binding to m6A-containing mRNA and promoting their degradation (PubMed:28106072). Recognizes and binds m6A-containing circular RNAs (circRNAs); circRNAs are generated through back-splicing of pre-mRNAs, a non-canonical splicing process promoted by dsRNA structures across circularizing exons (PubMed:28281539). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31388144, PubMed:31292544, PubMed:32451507). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind N1-methyladenosine (m1A)-containing mRNAs: inhibits trophoblast invasion by binding to m1A-methylated transcripts of IGF1R, promoting their degradation (PubMed:32194978). {ECO:0000250|UniProtKB:Q8BYK6, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:28106076, ECO:0000269|PubMed:28281539, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:32194978, ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.; FUNCTION: Has some antiviral activity against HIV-1 virus: incorporated into HIV-1 particles in a nucleocapsid-dependent manner and reduces viral infectivity in the next cycle of infection (PubMed:32053707). May interfere with this early step of the viral life cycle by binding to N6-methyladenosine (m6A) modified sites on the HIV-1 RNA genome (PubMed:32053707). {ECO:0000269|PubMed:32053707}. View more >>

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

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S218N	TCGA-19-5956	GBM	TCGA	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation rewiring degron network	0.25
p.R163I	TCGA-A5-A0G2	UCEC	TCGA	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.0833
p.R163I	DO41235	UCEC	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.0833
p.A164D	TCGA-AP-A0LM	UCEC	TCGA	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.0556
p.A164D	DO43306	UCEC	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.0556
p.Q141H	TCGA-AZ-6599	COAD	TCGA	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.0833
p.A210V	TCGA-B5-A11E	UCEC	TCGA	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation rewiring degron network	0.3056
p.Q141R	TCGA-BS-A0UV	UCEC	TCGA	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.0833
p.Q141R	DO42793	UCEC	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.0833
p.L161I	TCGA-CN-6010	HNSC	TCGA	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.1389
p.L161I	DO14766	HNSC	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.1389
p.S151N	TCGA-ND-A4WC	UCS	TCGA	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7069
p.S151N	SIDM00845	Burkitt's Lymphoma	GDSC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7069
p.S151N	SIDM00461	Acute Myeloid Leukemia	GDSC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7069
p.S151N	SIDM00946	T-Lymphoblastic Leukemia	GDSC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7069
p.S151N	SIDM01519	Head and Neck Carcinoma	GDSC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7069
p.S151N	DND-41	haematopoietic and lymphoid tissue	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7069
p.S151N	Daudi	haematopoietic and lymphoid tissue	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7069
p.S151N	OCI-AML5	haematopoietic and lymphoid tissue	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7069
p.S159R	TCGA-OR-A5KB	ACC	TCGA	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.1944
p.S159G	TCGA-VQ-A91S	STAD	TCGA	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.1944
p.A210T	DO227987	COCA	ICGC	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation rewiring degron network	0.3056
p.A148V	DO227996	COCA	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2778
p.P155H	DO233764	GACA	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation blocking phosphorylation signal	0.75
p.P146S	DO15334	HNSC	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2222
p.Q156H	DO49733	KIRC	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2778
p.G142E	DO50875	LICA	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.1111
p.P216S	DO222843	MELA	ICGC	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation rewiring degron network	0.3056
p.Q159H	DO28731	OV	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.1944
p.D218Y	DO36556	READ	ICGC	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation rewiring degron network	0.25
p.D218Y	DO43041	UCEC	ICGC	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation rewiring degron network	0.25
p.A210D	DO38328	STAD	ICGC	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation rewiring degron network	0.3056
p.R163H	DO219773	UCEC	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.0833
p.G143E	DO43186	UCEC	ICGC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.1389
p.V211E	SIDM00282	Colorectal Carcinoma	GDSC	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation altering degron motif	0.7693
p.V211E	CW-2	large intestine	COSMIC	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation altering degron motif	0.7693
p.S151I	SIDM00699	Small Cell Lung Carcinoma	GDSC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7341
p.S151I	NCI-H2141	lung	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation altering degron motif	0.7341
p.S147N	ACH-000981	Leukemia	CCLE	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.25
p.V207E	ACH-000998	Colon/Colorectal Cancer	CCLE	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation rewiring degron network	0.2222
p.S147I	ACH-001138	Lung Cancer	CCLE	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.25
p.S148N	DND-41	haematopoietic and lymphoid tissue	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2778
p.S148N	OCI-AML5	haematopoietic and lymphoid tissue	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2778
p.S148N	Daudi	haematopoietic and lymphoid tissue	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2778
p.S146I	NCI-H2141	lung	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2222
p.S146N	DND-41	haematopoietic and lymphoid tissue	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2222
p.S146N	Daudi	haematopoietic and lymphoid tissue	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2222
p.S146N	OCI-AML5	haematopoietic and lymphoid tissue	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2222
p.V208E	CW-2	large intestine	COSMIC	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation rewiring degron network	0.25
p.V157E	CW-2	large intestine	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.25
p.V206E	CW-2	large intestine	COSMIC	ALSSS	DEG_SPOP_SBC_1	211:215	Mutation substituting flanking lysine	0.3056
p.S148I	NCI-H2141	lung	COSMIC	AYSSS	DEG_SPOP_SBC_1	150:154	Mutation rewiring degron network	0.2778

Kaplan plot for YTHDF3 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

YTHDF3

UniProt ID: Q7Z739

Entrez ID: 253943

Protein name: YTH domain-containing family protein 3 (DF3)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for YTHDF3 in