DegronMD - Q96MU7(YTHDC1)

FUNCTION: Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R267Q	TCGA-AA-3984	COAD	TCGA	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.1944
p.R267Q	TCGA-AG-A002	READ	TCGA	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.1944
p.R267Q	TCGA-EO-A22X	UCEC	TCGA	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.1944
p.R267Q	DO9002	COAD	ICGC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.1944
p.R267Q	DO43907	UCEC	ICGC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.1944
p.D263G	TCGA-AA-A00N	COAD	TCGA	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.0833
p.D263G	DO9876	COAD	ICGC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.0833
p.R162H	TCGA-AN-A0AK	BRCA	TCGA	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.0556
p.R162H	DO1608	BRCA	ICGC	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.0556
p.D263Y	TCGA-AP-A056	UCEC	TCGA	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.0833
p.D263Y	DO43971	UCEC	ICGC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.0833
p.Q68H	TCGA-AP-A1DK	UCEC	TCGA	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.1944
p.Q68H	DO42033	UCEC	ICGC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.1944
p.D282Y	TCGA-AX-A2HC	UCEC	TCGA	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.1944
p.D282Y	DO224600	BRCA	ICGC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.1944
p.D282Y	DO1011	BRCA	ICGC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.1944
p.D282Y	DO41572	UCEC	ICGC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.1944
p.R154I	TCGA-BS-A0UV	UCEC	TCGA	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.2778
p.R154I	TCGA-D3-A2JP	SKCM	TCGA	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.2778
p.R154I	DO222762	COCA	ICGC	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.2778
p.R154I	DO47407	SKCM	ICGC	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.2778
p.R154I	DO42793	UCEC	ICGC	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.2778
p.P73Q	TCGA-D3-A2JD	SKCM	TCGA	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation altering degron motif	0.7035
p.P73Q	DO37543	SKCM	ICGC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation altering degron motif	0.7035
p.T87A	TCGA-DU-6407	LGG	TCGA	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.0556
p.T87A	DO22295	LGG	ICGC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.0556
p.V70A	TCGA-E6-A2P8	UCEC	TCGA	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.25
p.V70A	DO40924	UCEC	ICGC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.25
p.V70A	SIDM00678	Bladder Carcinoma	GDSC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.25
p.V70A	ACH-000724	Bladder Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.25
p.V70A	HT-1376	urinary tract	COSMIC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.25
p.E141K	TCGA-EA-A43B	CESC	TCGA	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.1667
p.E141K	DO44384	CESC	ICGC	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.1667
p.S66F	TCGA-EB-A3Y6	SKCM	TCGA	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.1389
p.S66F	DO38081	SKCM	ICGC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.1389
p.E153A	TCGA-EV-5902	KIRP	TCGA	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.3056
p.E153A	DO20875	KIRP	ICGC	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.3056
p.N81K	TCGA-F5-6861	READ	TCGA	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.2222
p.N81K	DO36888	READ	ICGC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.2222
p.Y264C	TCGA-IS-A3K8	SARC	TCGA	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation blocking phosphorylation signal	0.5556
p.Y264C	DO220170	SARC	ICGC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation blocking phosphorylation signal	0.5556
p.S271G	TCGA-UY-A9PB	BLCA	TCGA	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.3056
p.S271G	DO219041	BLCA	ICGC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation rewiring degron network	0.3056
p.H65R	DO23348	LINC	ICGC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.1111
p.R162C	SIDM01141	Ovarian Carcinoma	GDSC	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.0556
p.R162C	ACH-000291	Ovarian Cancer	CCLE	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation rewiring degron network	0.0556
p.S86T	SIDM00222	Mesothelioma	GDSC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.0833
p.S86T	ACH-000319	Lung Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.0833
p.S86T	MPP-89	pleura	COSMIC	PLSSS	DEG_SPOP_SBC_1	73:77	Mutation rewiring degron network	0.0833
p.D150N	SIDM01145	Gastric Carcinoma	GDSC	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation altering degron motif	0.5821
p.D150N	SIDM00658	Non-Small Cell Lung Carcinoma	GDSC	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation altering degron motif	0.5821
p.D272V	SIDM00250	Esophageal Squamous Cell Carcinoma	GDSC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation altering degron motif	0.7785
p.D272V	ACH-000917	Esophageal Cancer	CCLE	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation altering degron motif	0.7785
p.D272V	TE-4	oesophagus	COSMIC	DSGSES	DEG_SCF_TRCP1_1	272:277	Mutation altering degron motif	0.7785
p.P147S	ACH-000588	Myeloma	CCLE	PTPDGS	DEG_SCF_FBW7_1	147:152	Mutation altering degron motif	0.6752

Kaplan plot for YTHDC1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

YTHDC1

UniProt ID: Q96MU7

Entrez ID: 91746

Protein name: YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for YTHDC1 in