DegronMD - P26378(ELAVL4)

FUNCTION: RNA-binding protein that is involved in the post-transcriptional regulation of mRNAs (PubMed:7898713, PubMed:10710437, PubMed:12034726, PubMed:12468554, PubMed:17035636, PubMed:17234598). Plays a role in the regulation of mRNA stability, alternative splicing and translation (PubMed:7898713, PubMed:10710437, PubMed:12034726, PubMed:12468554, PubMed:17035636, PubMed:17234598). Binds to AU-rich element (ARE) sequences in the 3' untranslated region (UTR) of target mRNAs, including GAP43, VEGF, FOS, CDKN1A and ACHE mRNA (PubMed:7898713, PubMed:10710437, PubMed:12034726, PubMed:12468554). Many of the target mRNAs are coding for RNA-binding proteins, transcription factors and proteins involved in RNA processing and/or neuronal development and function (By similarity). By binding to the mRNA 3'UTR, decreases mRNA deadenylation and thereby contributes to the stabilization of mRNA molecules and their protection from decay (PubMed:12034726). Also binds to the polyadenylated (poly(A)) tail in the 3'UTR of mRNA, thereby increasing its affinity for mRNA binding (PubMed:12034726). Mainly plays a role in neuron-specific RNA processing by stabilization of mRNAs such as GAP43, ACHE and mRNAs of other neuronal proteins, thereby contributing to the differentiation of neural progenitor cells, nervous system development, learning and memory mechanisms (PubMed:12034726, PubMed:12468554, PubMed:17234598, PubMed:18218628). Involved in the negative regulation of the proliferative activity of neuronal stem cells and in the positive regulation of neuronal differentiation of neural progenitor cells (By similarity). Promotes neuronal differentiation of neural stem/progenitor cells in the adult subventricular zone of the hippocampus by binding to and stabilizing SATB1 mRNA (By similarity). Binds and stabilizes MSI1 mRNA in neural stem cells (By similarity). Exhibits increased binding to ACHE mRNA during neuronal differentiation, thereby stabilizing ACHE mRNA and enhancing its expression (PubMed:12468554, PubMed:17234598). Protects CDKN1A mRNA from decay by binding to its 3'-UTR (By similarity). May bind to APP and BACE1 mRNAS and the BACE1AS lncRNA and enhance their stabilization (PubMed:24857657). Plays a role in neurite outgrowth and in the establishment and maturation of dendritic arbors, thereby contributing to neocortical and hippocampal circuitry function (By similarity). Stabilizes GAP43 mRNA and protects it from decay during postembryonic development in the brain (PubMed:12034726). By promoting the stabilization of GAP43 mRNA, plays a role in NGF-mediated neurite outgrowth (By similarity). Binds to BDNF long 3'UTR mRNA, thereby leading to its stabilization and increased dendritic translation after activation of PKC (By similarity). By increasing translation of BDNF after nerve injury, may contribute to nerve regeneration (By similarity). Acts as a stabilizing factor by binding to the 3'UTR of NOVA1 mRNA, thereby increasing its translation and enhancing its functional activity in neuron-specific splicing (PubMed:18218628). Stimulates translation of mRNA in a poly(A)- and cap-dependent manner, possibly by associating with the EIF4F cap-binding complex (By similarity). May also negatively regulate translation by binding to the 5'UTR of Ins2 mRNA, thereby repressing its translation (By similarity). Upon glucose stimulation, Ins2 mRNA is released from ELAVL4 and translational inhibition is abolished (By similarity). Also plays a role in the regulation of alternative splicing (PubMed:17035636). May regulate alternative splicing of CALCA pre-mRNA into Calcitonin and Calcitonin gene-related peptide 1 (CGRP) by competing with splicing regulator TIAR for binding to U-rich intronic sequences of CALCA pre-mRNA (PubMed:17035636). {ECO:0000250|UniProtKB:O09032, ECO:0000250|UniProtKB:Q61701, ECO:0000269|PubMed:10710437, ECO:0000269|PubMed:12034726, ECO:0000269|PubMed:12468554, ECO:0000269|PubMed:17035636, ECO:0000269|PubMed:17234598, ECO:0000269|PubMed:18218628, ECO:0000269|PubMed:24857657, ECO:0000269|PubMed:7898713}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R249C	TCGA-56-8624	LUSC	TCGA	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.8301
p.R249L	TCGA-56-8624	LUSC	TCGA	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.8428
p.R248Q	TCGA-AA-3955	COAD	TCGA	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.7329
p.R248Q	TCGA-D3-A2JF	SKCM	TCGA	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.7329
p.P246S	TCGA-EE-A3JD	SKCM	TCGA	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.3056
p.H255Y	TCGA-FW-A3R5	SKCM	TCGA	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.7229
p.L263M	TCGA-IB-7651	PAAD	TCGA	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.1111
p.Q259H	TCGA-VS-A8EL	CESC	TCGA	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation blocking phosphorylation signal	0.6667
p.Q247H	DO51624	CESC	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.647
p.M257I	DO16061	HNSC	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.2778
p.R250S	DO229008	LICA	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.6316
p.R237L	DO45500	LUSC	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.0556
p.R237C	DO45500	LUSC	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.0556
p.A258V	DO232842	NACA	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.25
p.A258V	DO232224	PBCA	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.25
p.L251M	DO46657	PAAD	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.711
p.V261I	DO228596	PRAD	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.1667
p.H243Y	DO37406	SKCM	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.2222
p.H243Y	SW684	soft tissue	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.2222
p.S265F	DO51290	SKCM	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.0556
p.L255F	DO38380	STAD	ICGC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.587
p.K244T	SIDM02020	Esophageal Carcinoma	GDSC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.25
p.S250I	SIDM01090	Colorectal Carcinoma	GDSC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.7341
p.S250I	RKO	large intestine	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation altering degron motif	0.7341
p.S259F	SIDM00217	Colorectal Carcinoma	GDSC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation blocking phosphorylation signal	0.6667
p.S259F	SNU-1040	large intestine	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation blocking phosphorylation signal	0.6667
p.H238R	ACH-000991	Colon/Colorectal Cancer	CCLE	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation blocking phosphorylation signal	0.5278
p.H238R	SNU-81	large intestine	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation blocking phosphorylation signal	0.5278
p.H238Y	ACH-002309	Sarcoma	CCLE	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation blocking phosphorylation signal	0.5278
p.H238Y	SW684	soft tissue	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation blocking phosphorylation signal	0.5278
p.H241Y	SW684	soft tissue	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.1667
p.H243R	SNU-81	large intestine	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.2222
p.H241R	SNU-81	large intestine	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.1667
p.P239T	NCI-H661	lung	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.1111
p.P237T	NCI-H661	lung	COSMIC	QRFRLDNLL	DEG_APCC_DBOX_1	247:255	Mutation rewiring degron network	0.0556

Kaplan plot for ELAVL4 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

ELAVL4

UniProt ID: P26378

Entrez ID: 1996

Protein name: ELAV-like protein 4 (Hu-antigen D) (HuD) (Paraneoplastic encephalomyelitis antigen HuD)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for ELAVL4 in