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Showing Protein ELAV-like protein 4 (HMDBP12704)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP12704
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: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).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
mRNA processing
RNA processing
RNA splicing
3'-UTR-mediated mRNA stabilization
positive regulation of 3'-UTR-mediated mRNA stabilization
Cellular Component
cytoplasm
axon
dendrite
growth cone
perikaryon
ribonucleoprotein complex
Molecular Function
mRNA 3'-UTR binding
poly(A) RNA binding
mRNA 3'-UTR AU-rich region binding
pre-mRNA intronic pyrimidine-rich binding
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 366
Molecular Weight 42397.95
Theoretical pI 9.386
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P26378
UniProtKB/Swiss-Prot Entry Name ELAV4_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  4. Zhu H, Hasman RA, Barron VA, Luo G, Lou H: A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators. Mol Biol Cell. 2006 Dec;17(12):5105-14. doi: 10.1091/mbc.e06-02-0099. Epub 2006 Oct 11. [PubMed:17035636 ]
  5. Ratti A, Fallini C, Colombrita C, Pascale A, Laforenza U, Quattrone A, Silani V: Post-transcriptional regulation of neuro-oncological ventral antigen 1 by the neuronal RNA-binding proteins ELAV. J Biol Chem. 2008 Mar 21;283(12):7531-41. doi: 10.1074/jbc.M706082200. Epub 2008 Jan 24. [PubMed:18218628 ]
  6. Fallini C, Zhang H, Su Y, Silani V, Singer RH, Rossoll W, Bassell GJ: The survival of motor neuron (SMN) protein interacts with the mRNA-binding protein HuD and regulates localization of poly(A) mRNA in primary motor neuron axons. J Neurosci. 2011 Mar 9;31(10):3914-25. doi: 10.1523/JNEUROSCI.3631-10.2011. [PubMed:21389246 ]
  7. 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 ]
  8. 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 ]
  9. Szabo A, Dalmau J, Manley G, Rosenfeld M, Wong E, Henson J, Posner JB, Furneaux HM: HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. Cell. 1991 Oct 18;67(2):325-33. doi: 10.1016/0092-8674(91)90184-z. [PubMed:1655278 ]
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  12. King PH: RNA-binding analyses of HuC and HuD with the VEGF and c-myc 3'-untranslated regions using a novel ELISA-based assay. Nucleic Acids Res. 2000 Apr 1;28(7):E20. doi: 10.1093/nar/28.7.e20. [PubMed:10710437 ]
  13. Beckel-Mitchener AC, Miera A, Keller R, Perrone-Bizzozero NI: Poly(A) tail length-dependent stabilization of GAP-43 mRNA by the RNA-binding protein HuD. J Biol Chem. 2002 Aug 2;277(31):27996-8002. doi: 10.1074/jbc.M201982200. Epub 2002 May 28. [PubMed:12034726 ]
  14. Fujiwara T, Mori Y, Chu DL, Koyama Y, Miyata S, Tanaka H, Yachi K, Kubo T, Yoshikawa H, Tohyama M: CARM1 regulates proliferation of PC12 cells by methylating HuD. Mol Cell Biol. 2006 Mar;26(6):2273-85. doi: 10.1128/MCB.26.6.2273-2285.2006. [PubMed:16508003 ]
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