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Showing Protein ELAV-like protein 4 (HMDBP12703)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP12703
Secondary Accession Numbers None
Name ELAV-like protein 4
Synonyms
  1. Hu-antigen D
  2. Paraneoplastic encephalomyelitis antigen HuD
  3. HuD
Gene Name ELAVL4
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function RNA-binding protein that is involved in the post-transcriptional regulation of mRNAs (PubMed:15764704, PubMed:16554442, PubMed:17035636, PubMed:20064466, PubMed:22387028, PubMed:23383270, PubMed:26305964, PubMed:28111162). Plays a role in the regulation of mRNA stability, alternative splicing and translation (PubMed:15764704, PubMed:23383270, PubMed:26305964, PubMed:28111162). Binds to AU-rich element (ARE) sequences in the 3' untranslated region (3'UTR) of target mRNAs, including GAP43, VEGF, FOS, CDKN1A and ACHE mRNA (By similarity). 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 (PubMed:26305964). 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 (PubMed:20064466). 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:15764704, PubMed:16554442, PubMed:18218628, PubMed:23383270, PubMed:24599466, PubMed:25692578, PubMed:26305964, PubMed:28111162). 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 (PubMed:15764704). Promotes neuronal differentiation of neural stem/progenitor cells in the adult subventricular zone of the hippocampus by binding to and stabilizing SATB1 mRNA (PubMed:26305964). Binds and stabilizes MSI1 mRNA in neural stem cells (PubMed:16554442). 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 (By similarity). 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 (PubMed:24599466). Stabilizes GAP43 mRNA and protects it from decay during postembryonic development in the brain (PubMed:28111162). 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 (PubMed:23383270, PubMed:25692578). By increasing translation of BDNF after nerve injury, may contribute to nerve regeneration (PubMed:28111162). 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 (PubMed:20064466). May also negatively regulate translation by binding to the 5'UTR of Ins2 mRNA, thereby repressing its translation (PubMed:22387028). Upon glucose stimulation, Ins2 mRNA is released from ELAVL4 and translational inhibition is abolished (PubMed:22387028). 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 sequences of CALCA pre-mRNA (PubMed:17035636).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
mRNA processing
cerebral cortex neuron differentiation
RNA splicing
associative learning
RNA processing
dendrite morphogenesis
learning
response to cocaine
response to endoplasmic reticulum stress
neuron differentiation
regulation of mRNA stability
locomotory behavior
aging
3'-UTR-mediated mRNA stabilization
cellular response to nerve growth factor stimulus
positive regulation of 3'-UTR-mediated mRNA stabilization
positive regulation of dendrite development
regeneration
regulation of translation at synapse, modulating synaptic transmission
Cellular Component
cytoplasm
polysomal ribosome
glutamatergic synapse
nuclear envelope
perikaryon
growth cone
cytoskeleton
neuronal cell body
dendrite
axon
membrane
nucleus
cytosol
Molecular Function
mRNA binding
poly(A) RNA binding
mRNA 3'-UTR binding
mRNA 3'-UTR AU-rich region binding
pre-mRNA intronic pyrimidine-rich binding
translation regulator activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 385
Molecular Weight 42367.92
Theoretical pI 9.38
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q61701
UniProtKB/Swiss-Prot Entry Name ELAV4_MOUSE
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  8. Quattrone A, Pascale A, Nogues X, Zhao W, Gusev P, Pacini A, Alkon DL: Posttranscriptional regulation of gene expression in learning by the neuronal ELAV-like mRNA-stabilizing proteins. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11668-73. doi: 10.1073/pnas.191388398. [PubMed:11573004 ]
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  19. Lee EK, Kim W, Tominaga K, Martindale JL, Yang X, Subaran SS, Carlson OD, Mercken EM, Kulkarni RN, Akamatsu W, Okano H, Perrone-Bizzozero NI, de Cabo R, Egan JM, Gorospe M: RNA-binding protein HuD controls insulin translation. Mol Cell. 2012 Mar 30;45(6):826-35. doi: 10.1016/j.molcel.2012.01.016. Epub 2012 Mar 1. [PubMed:22387028 ]
  20. Allen M, Bird C, Feng W, Liu G, Li W, Perrone-Bizzozero NI, Feng Y: HuD promotes BDNF expression in brain neurons via selective stabilization of the BDNF long 3'UTR mRNA. PLoS One. 2013;8(1):e55718. doi: 10.1371/journal.pone.0055718. Epub 2013 Jan 31. [PubMed:23383270 ]
  21. Kang MJ, Abdelmohsen K, Hutchison ER, Mitchell SJ, Grammatikakis I, Guo R, Noh JH, Martindale JL, Yang X, Lee EK, Faghihi MA, Wahlestedt C, Troncoso JC, Pletnikova O, Perrone-Bizzozero N, Resnick SM, de Cabo R, Mattson MP, Gorospe M: HuD regulates coding and noncoding RNA to induce APP-->Abeta processing. Cell Rep. 2014 Jun 12;7(5):1401-1409. doi: 10.1016/j.celrep.2014.04.050. Epub 2014 May 22. [PubMed:24857657 ]
  22. Vanevski F, Xu B: HuD interacts with Bdnf mRNA and is essential for activity-induced BDNF synthesis in dendrites. PLoS One. 2015 Feb 18;10(2):e0117264. doi: 10.1371/journal.pone.0117264. eCollection 2015. [PubMed:25692578 ]
  23. Wang F, Tidei JJ, Polich ED, Gao Y, Zhao H, Perrone-Bizzozero NI, Guo W, Zhao X: Positive feedback between RNA-binding protein HuD and transcription factor SATB1 promotes neurogenesis. Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):E4995-5004. doi: 10.1073/pnas.1513780112. Epub 2015 Aug 24. [PubMed:26305964 ]
  24. Sanna MD, Ghelardini C, Galeotti N: HuD-mediated distinct BDNF regulatory pathways promote regeneration after nerve injury. Brain Res. 2017 Mar 15;1659:55-63. doi: 10.1016/j.brainres.2017.01.019. Epub 2017 Jan 19. [PubMed:28111162 ]