O09032 · ELAV4_RAT
- ProteinELAV-like protein 4
- GeneElavl4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids385 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
RNA-binding protein that is involved in the post-transcriptional regulation of mRNAs (PubMed:10982410, PubMed:16508003, PubMed:17577668).
Plays a role in the regulation of mRNA stability, alternative splicing and translation (PubMed:10982410, PubMed:16508003, PubMed:17577668).
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:10982410).
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 (By similarity).
Also binds to the polyadenylated (poly(A)) tail in the 3'UTR of mRNA, thereby increasing its affinity for mRNA binding (By similarity).
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:10982410, PubMed:17577668).
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 (By similarity).
Protects CDKN1A mRNA from decay by binding to its 3'-UTR (PubMed:16508003).
May bind to APP and BACE1 mRNAS and the BACE1AS lncRNA and enhance their stabilization (By similarity).
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:10982410, PubMed:17234598).
By promoting the stabilization of GAP43 mRNA, plays a role in NGF-mediated neurite outgrowth (PubMed:10982410).
Binds to BDNF long 3'UTR mRNA, thereby leading to its stabilization and increased dendritic translation after activation of PKC (PubMed:25692578).
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 (By similarity).
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 form ELAVL4 and translational inhibition is abolished (By similarity).
Also plays a role in the regulation of alternative splicing (By similarity).
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 sequences of CALCA pre-mRNA (By similarity).
Plays a role in the regulation of mRNA stability, alternative splicing and translation (PubMed:10982410, PubMed:16508003, PubMed:17577668).
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:10982410).
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 (By similarity).
Also binds to the polyadenylated (poly(A)) tail in the 3'UTR of mRNA, thereby increasing its affinity for mRNA binding (By similarity).
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:10982410, PubMed:17577668).
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 (By similarity).
Protects CDKN1A mRNA from decay by binding to its 3'-UTR (PubMed:16508003).
May bind to APP and BACE1 mRNAS and the BACE1AS lncRNA and enhance their stabilization (By similarity).
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:10982410, PubMed:17234598).
By promoting the stabilization of GAP43 mRNA, plays a role in NGF-mediated neurite outgrowth (PubMed:10982410).
Binds to BDNF long 3'UTR mRNA, thereby leading to its stabilization and increased dendritic translation after activation of PKC (PubMed:25692578).
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 (By similarity).
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 form ELAVL4 and translational inhibition is abolished (By similarity).
Also plays a role in the regulation of alternative splicing (By similarity).
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 sequences of CALCA pre-mRNA (By similarity).
GO annotations
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameELAV-like protein 4
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionO09032
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Co-localizes with ribosomal RNA in polysomes.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Faster decay of GAP42 mRNA.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000081585 | 1-385 | ELAV-like protein 4 | |||
Sequence: MEWNGLKMIISTMEPQVSNGPTSNTSNGPSSNNRNCPSPMQTGAATDDSKTNLIVNYLPQNMTQEEFRSLFGSIGEIESCKLVRDKITGQSLGYGFVNYIDPKDAEKAINTLNGLRLQTKTIKVSYARPSSASIRDANLYVSGLPKTMTQKELEQLFSQYGRIITSRILVDQVTGVSRGVGFIRFDKRIEAEEAIKGLNGQKPSGATEPITVKFANNPSQKSSQALLSQLYQSPNRRYPGPLHHQAQRFRLDNLLNMAYGVKRLMSGPVPPSACPPRFSPITIDGMTSLVGMNIPGHTGTGWCIFVYNLSPDSDESVLWQLFGPFGAVNNVKVIRDFNTNKCKGFGFVTMTNYDEAAMAIASLNGYRLGDRVLQVSFKTNKAHKS | ||||||
Modified residue | 38 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 233 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 248 | Asymmetric dimethylarginine; by CARM1; alternate | ||||
Sequence: R | ||||||
Modified residue | 248 | Omega-N-methylarginine; by CARM1; alternate | ||||
Sequence: R |
Post-translational modification
Methylated by CARM1, which leads to reduced RNA-binding activity and enhanced interaction with SMN (By similarity).
Methylation at Arg-248 by CARM1 weakens protective binding to the 3'-UTR of CDKN1A mRNA and down-regulates CDKN1A protein expression, thereby maintaining cells in a proliferative state (PubMed:16508003).
Methylation is inhibited by NGF, which facilitates neurite outgrowth (PubMed:16508003).
Methylation at Arg-248 by CARM1 weakens protective binding to the 3'-UTR of CDKN1A mRNA and down-regulates CDKN1A protein expression, thereby maintaining cells in a proliferative state (PubMed:16508003).
Methylation is inhibited by NGF, which facilitates neurite outgrowth (PubMed:16508003).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the hippocampus and cerebral cortex (at protein level) (PubMed:15519747).
Expressed in stem and progenitor cells in the subventricular zone of the hippocampus (at protein level) (PubMed:16554442).
Expressed in hippocampal neurons, with highest levels of expression in the CA4 and CA3 neurons and lower levels in CA1 neurons (at protein level) (PubMed:11948657, PubMed:17577668, PubMed:25692578).
Expressed in the dorsal root ganglion (at protein level) (PubMed:12957493).
Expressed in the superior cervical ganglion (PubMed:17234598).
Expressed in stem and progenitor cells in the subventricular zone of the hippocampus (at protein level) (PubMed:16554442).
Expressed in hippocampal neurons, with highest levels of expression in the CA4 and CA3 neurons and lower levels in CA1 neurons (at protein level) (PubMed:11948657, PubMed:17577668, PubMed:25692578).
Expressed in the dorsal root ganglion (at protein level) (PubMed:12957493).
Expressed in the superior cervical ganglion (PubMed:17234598).
Induction
Up-regulated by kainic acid-induced seizures (PubMed:17577668).
Up-regulated after contextual fear conditioning (PubMed:15519747).
Down-regulated at day 2 after axotomy and up-regulated at day 7 after axotomy (PubMed:12957493, PubMed:17234598).
Up-regulated after contextual fear conditioning (PubMed:15519747).
Down-regulated at day 2 after axotomy and up-regulated at day 7 after axotomy (PubMed:12957493, PubMed:17234598).
Developmental stage
Expression in dentate granule cells of the hippocampus at postnatal day 7, with disappearing expression in dentate granule cells as early as P14.
Gene expression databases
Interaction
Subunit
Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP (By similarity).
Associates with the EIF4F cap-binding complex, composed of EIF4G, EIF4A, EIF4E and PABP (By similarity).
Within the EIF4F cap-binding complex, interacts with EIF4A (By similarity).
Interacts with SMN (via Tudor domain) in an RNA-independent manner; the interaction is required for localization of ELAVL4 to RNA granules (PubMed:21389246).
Interacts with MAP1 light chain LC1 (via C-terminus); the interaction contributes to the association of ELAVL4 with microtubules (By similarity).
Interacts with MAP1 light chain LC2 (By similarity).
Associates with the EIF4F cap-binding complex, composed of EIF4G, EIF4A, EIF4E and PABP (By similarity).
Within the EIF4F cap-binding complex, interacts with EIF4A (By similarity).
Interacts with SMN (via Tudor domain) in an RNA-independent manner; the interaction is required for localization of ELAVL4 to RNA granules (PubMed:21389246).
Interacts with MAP1 light chain LC1 (via C-terminus); the interaction contributes to the association of ELAVL4 with microtubules (By similarity).
Interacts with MAP1 light chain LC2 (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 12-48 | Disordered | ||||
Sequence: TMEPQVSNGPTSNTSNGPSSNNRNCPSPMQTGAATDD | ||||||
Domain | 51-129 | RRM 1 | ||||
Sequence: TNLIVNYLPQNMTQEEFRSLFGSIGEIESCKLVRDKITGQSLGYGFVNYIDPKDAEKAINTLNGLRLQTKTIKVSYARP | ||||||
Domain | 137-217 | RRM 2 | ||||
Sequence: ANLYVSGLPKTMTQKELEQLFSQYGRIITSRILVDQVTGVSRGVGFIRFDKRIEAEEAIKGLNGQKPSGATEPITVKFANN | ||||||
Domain | 302-380 | RRM 3 | ||||
Sequence: WCIFVYNLSPDSDESVLWQLFGPFGAVNNVKVIRDFNTNKCKGFGFVTMTNYDEAAMAIASLNGYRLGDRVLQVSFKTN |
Domain
The RRM 3 domain is required for binding to poly(A) RNA, for the association with polysomes and with the EIF4F cap-binding complex and for the stimulation of translation (By similarity).
The RRM 1 and RRM 2 domains may contribute to polysome association and stimulation of translation (By similarity).
The RRM 1 and RRM 2 domains may contribute to polysome association and stimulation of translation (By similarity).
Sequence similarities
Belongs to the RRM elav family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
This entry describes 1 isoforms produced by Alternative splicing. At least 3 isoforms are produced.
O09032-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length385
- Mass (Da)42,368
- Last updated2019-09-18 v2
- Checksum1EA9CDAB7E9BC683
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6AI53 | A0A8I6AI53_RAT | Elavl4 | 365 | ||
A0A8I6APY9 | A0A8I6APY9_RAT | Elavl4 | 380 | ||
A0A8I6AV49 | A0A8I6AV49_RAT | Elavl4 | 366 | ||
A0A8I6ADY8 | A0A8I6ADY8_RAT | Elavl4 | 383 | ||
A0A8I6A344 | A0A8I6A344_RAT | Elavl4 | 346 | ||
A0A8I5ZNE4 | A0A8I5ZNE4_RAT | Elavl4 | 377 | ||
A0A8I5Y0H9 | A0A8I5Y0H9_RAT | Elavl4 | 356 |
Sequence caution
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S83320 EMBL· GenBank· DDBJ | AAB50733.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AABR07049591 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AABR07049592 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |