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ELAVL1 (ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R))

Identity

Other namesELAV1
HUR
HuR
Hua
MelG
HGNC (Hugo) ELAVL1
LocusID (NCBI) 1994
Location 19p13.2
Location_base_pair Starts at 8023457 and ends at 8070529 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
Description The ELAV1 gene, located on the minus strand, encompasses 47072 bp with 6 exons and 5 introns.
Transcription mRNA of 2,3 kb but a second putative poly(A) signal is described leading to a 6 kb mRNA.
Coding sequence from 168 to 1148 b.

Protein

 
Description The HuR protein consists of 326 aa (36 kDa). HuR has three highly conserved motifs belonging to the RNA recognition motif (RRM) superfamily and a hinge region between RRMs 2 and 3 named the HuR nucleocytoplasmic shuttling (HNS) domain. It has been shown that the HNS domain regulates the localization of HuR by mediating its association with adaptor proteins for nuclear export such as pp32/PHAP-I and APRIL and with import factors transportin-1, transportin-2, and importin.
Expression Ubiquitously expressed
Localisation Predominantly nuclear but shuttles between the nuclear and the cytoplasm.
Function HuR belongs to the ELAV/Hu family (embryonic lethal abnormal vision phenotype in flies) of RNA-binding proteins (RBPs). Like other Hu/ELAVL RBPs, HuR contains 3 RRM through which it binds to specific mRNA and influences their post-transcriptional expression. HuR exhibits a high affinity for adenosine and uracil- (AU-) rich elements (ARE) leading to the stabilization and/or transport of its target host messages. In addition to its role as an mRNA stabilizer and transporter, HuR has been shown to mediate the translation of mRNAs and rarely to repress translation. Moreover, HuR plays a key role in the enhancement of caspase-dependent apoptosis induced by extreme stress conditions. In response to a lethal stress, HuR accumulates in the cytoplasm, where it undergoes caspase-mediated cleavage. This cleavage appears to be important for pp32/PHAP-I - mediated enhancement of the caspase-dependent apoptosis. HuR was shown to play others critical functions in cells responding to immune stimuli, nutrient availability, and exposure to damaging agents. Similarly, it has an important regulatory function in the progression of cells through the division cycle, the implementation of differentiation programs, the promotion of cell migration, cell invasion and a malignant phenotype, and the inhibition of replicative senescence.

Mutations

Note No HuR mutations have been found in cancer or other diseases.

Implicated in

Entity Cancer
Oncogenesis Breast , Lung , Colon and Ovary cancer. Expression of HuR is increased in all cancer tissues compared to the normal-tissue counterparts. It exists a consistent correlation between HuR expression levels and advancing stages of malignancy.
  
Entity Cachexia
Disease Cachexia, characterized by the excessive loss of skeletal muscle, is frequently seen in patients with chronic diseases such as cancer. The bioactive gas nitric oxide has been identified as an important player in cancer-induced cachexia because NO is directly involved in the loss of MyoD mRNA (a key factor needed for the myogenic process, which is destabilized during cachexia) and muscle fiber. These events are mediated by the ability of HuR to associate and stabilizes the message encoding the inducible NO synthase enzyme.
  
Entity Hypertension
Disease Chronic hypertension is associated with functional and morphological alterations of the vessel wall (ie, dysfunctional vascular endothelium and thickening of the smooth muscle layer). The pathomechanisms accounting for hypertension-induced vascular alterations are likely to be multifactorial. HuR is not only an important factor controlling vascular gene expression, but it is also subject to control by vasoactive factors that regulate cGMP and cAMP levels and downregulate its expression.
  
Entity Paraneoplastic neurological disease
Disease Paraneoplastic enecephalomyelitis/sensory neuronopathy (PEM/SSN) is characterized by the presence of a common autoantibody, referred to as anti-Hu or type I anti-neuronal nuclear antibody (ANNA-1). The target of these antibodies is the family of Hu antigens (Hel-N1, HuC, HuD and HuR).
  

External links

Nomenclature
HGNC (Hugo)ELAVL1   3312
Cards
AtlasELAVL1ID44237ch19p13
Entrez_Gene (NCBI)ELAVL1  1994  ELAV like RNA binding protein 1
GeneCards (Weizmann)ELAVL1
Ensembl (Hinxton)ENSG00000066044 [Gene_View]  chr19:8023457-8070529 [Contig_View]  ELAVL1 [Vega]
ICGC DataPortalENSG00000066044
AceView (NCBI)ELAVL1
Genatlas (Paris)ELAVL1
WikiGenes1994
SOURCE (Princeton)NM_001419
Genomic and cartography
GoldenPath (UCSC)ELAVL1  -  19p13.2   chr19:8023457-8070529 -  19p13.2   [Description]    (hg19-Feb_2009)
EnsemblELAVL1 - 19p13.2 [CytoView]
Mapping of homologs : NCBIELAVL1 [Mapview]
OMIM603466   
Gene and transcription
Genbank (Entrez)AI375368 AK022334 AK096659 AK301013 AL713686
RefSeq transcript (Entrez)NM_001419
RefSeq genomic (Entrez)AC_000151 NC_000019 NC_018930 NT_011295 NW_001838480 NW_004929413
Consensus coding sequences : CCDS (NCBI)ELAVL1
Cluster EST : UnigeneHs.713744 [ NCBI ]
CGAP (NCI)Hs.713744
Alternative Splicing : Fast-db (Paris)GSHG0015453
Alternative Splicing GalleryENSG00000066044
Gene ExpressionELAVL1 [ NCBI-GEO ]     ELAVL1 [ SEEK ]   ELAVL1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15717 (Uniprot)
NextProtQ15717  [Medical]
With graphics : InterProQ15717
Splice isoforms : SwissVarQ15717 (Swissvar)
Domaine pattern : Prosite (Expaxy)RRM (PS50102)   
Domains : Interpro (EBI)ELAD_HUD_SF    Hud_Sxl_RNA    Nucleotide-bd_a/b_plait    RRM_dom   
Related proteins : CluSTrQ15717
Domain families : Pfam (Sanger)RRM_1 (PF00076)   
Domain families : Pfam (NCBI)pfam00076   
Domain families : Smart (EMBL)RRM (SM00360)  
DMDM Disease mutations1994
Blocks (Seattle)Q15717
PDB (SRS)3HI9    4ED5    4EGL    4FXV   
PDB (PDBSum)3HI9    4ED5    4EGL    4FXV   
PDB (IMB)3HI9    4ED5    4EGL    4FXV   
PDB (RSDB)3HI9    4ED5    4EGL    4FXV   
Human Protein AtlasENSG00000066044
Peptide AtlasQ15717
HPRD16025
IPIIPI00940851   IPI00301936   
Protein Interaction databases
DIP (DOE-UCLA)Q15717
IntAct (EBI)Q15717
FunCoupENSG00000066044
BioGRIDELAVL1
IntegromeDBELAVL1
STRING (EMBL)ELAVL1
Ontologies - Pathways
QuickGOQ15717
Ontology : AmiGOnucleotide binding  RNA binding  double-stranded RNA binding  mRNA binding  mRNA 3'-UTR binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  multicellular organismal development  gene expression  membrane  RNA metabolic process  mRNA metabolic process  AU-rich element binding  protein kinase binding  mRNA 3'-UTR AU-rich region binding  poly(A) RNA binding  positive regulation of translation  mRNA stabilization  mRNA stabilization  3'-UTR-mediated mRNA stabilization  3'-UTR-mediated mRNA stabilization  regulation of stem cell maintenance  
Ontology : EGO-EBInucleotide binding  RNA binding  double-stranded RNA binding  mRNA binding  mRNA 3'-UTR binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  multicellular organismal development  gene expression  membrane  RNA metabolic process  mRNA metabolic process  AU-rich element binding  protein kinase binding  mRNA 3'-UTR AU-rich region binding  poly(A) RNA binding  positive regulation of translation  mRNA stabilization  mRNA stabilization  3'-UTR-mediated mRNA stabilization  3'-UTR-mediated mRNA stabilization  regulation of stem cell maintenance  
Pathways : BIOCARTAVEGF, Hypoxia, and Angiogenesis [Genes]   
REACTOMEQ15717 [protein]
REACTOME PathwaysREACT_71 Gene Expression [pathway]
REACTOME PathwaysREACT_21257 Metabolism of RNA [pathway]
Protein Interaction DatabaseELAVL1
Wikipedia pathwaysELAVL1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ELAVL1
SNP (GeneSNP Utah)ELAVL1
SNP : HGBaseELAVL1
Genetic variants : HAPMAPELAVL1
1000_GenomesELAVL1 
ICGC programENSG00000066044 
CONAN: Copy Number AnalysisELAVL1 
Somatic Mutations in Cancer : COSMICELAVL1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DECIPHER (Syndromes)19:8023457-8070529
Mutations and Diseases : HGMDELAVL1
OMIM603466   
MedgenELAVL1
GENETestsELAVL1
Disease Genetic AssociationELAVL1
Huge Navigator ELAVL1 [HugePedia]  ELAVL1 [HugeCancerGEM]
Genomic VariantsELAVL1  ELAVL1 [DGVbeta]
Exome VariantELAVL1
dbVarELAVL1
ClinVarELAVL1
snp3D : Map Gene to Disease1994
DGIdb (Curated mutations)ELAVL1
DGIdb (Drug Gene Interaction db)ELAVL1
General knowledge
Homologs : HomoloGeneELAVL1
Homology/Alignments : Family Browser (UCSC)ELAVL1
Phylogenetic Trees/Animal Genes : TreeFamELAVL1
Chemical/Protein Interactions : CTD1994
Chemical/Pharm GKB GenePA27740
Clinical trialELAVL1
Cancer Resource (Charite)ENSG00000066044
Other databases
Probes
Litterature
PubMed279 Pubmed reference(s) in Entrez
CoreMineELAVL1
GoPubMedELAVL1
iHOPELAVL1

Bibliography

Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs.
Fan XC, Steitz JA.
EMBO J. 1998 Jun 15; 17(12): 3448-3460.
PMID 9628880
 
Hu antigen specificities of ANNA-I autoantibodies in paraneoplastic neurological disease.
King PH, Redden D, Palmgren JS, Nabors LB, Lennon VA.
J Autoimmun. 1999 Dec; 13(4): 435-443.
PMID 10585760
 
HuR and mRNA stability.
Brennan CM, Steitz JA.
Cell Mol Life Sci. 2001 Feb; 58(2): 266-277. Review.
PMID 11289308
 
RNAi-mediated HuR depletion leads to the inhibition of muscle cell differentiation.
van der Giessen K, Di-Marco S, Clair E, Gallouzi IE.
J Biol Chem. 2003 Nov 21; 278(47): 47119-47128.
PMID 12944397
 
NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release.
Di Marco S, Mazroui R, Dallaire P, Chittur S, Tenenbaum SA, Radzioch D, Marette A, Gallouzi IE.
Mol Cell Biol. 2005 Aug; 25(15): 6533-6545.
PMID 16024790
 
Human-antigen R (HuR) expression in hypertension: downregulation of the mRNA stabilizing protein HuR in genetic hypertension.
Kloss S, Rodenbach D, Bordel R, Mulsch A.
Hypertension. 2005 Jun; 45(6): 1200-1206.
PMID 15883232
 
HuR: post-transcriptional paths to malignancy.
Lopez de Silanes I, Lal A, Gorospe M.
RNA Biol. 2005 Jan; 2(1): 11-13.
PMID 17132932
 
The RNA-binding protein HuR promotes cell migration and cell invasion by stabilizing the beta-actin mRNA in a U-rich-element-dependent manner.
Dormoy-Raclet V, Menard I, Clair E, Kurban G, Mazroui R, Di Marco S, von Roretz C, Pause A, Gallouzi IE.
Mol Cell Biol. 2007 Aug; 27(15): 5365-5380.
PMID 17548472
 
Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis.
Mazroui R, Di Marco S, Clair E, von Roretz C, Tenenbaum SA, Keene JD, Saleh M, Gallouzi IE.
J Cell Biol. 2008 Jan 14; 180(1): 113-127.
PMID 18180367
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written09-2008Virginie Dormoy-Raclet, Imed-Eddine Gallouzi
Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada

Citation

This paper should be referenced as such :
Dormoy-Raclet, V ; Gallouzi, IE
ELAVL1 (ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R))
Atlas Genet Cytogenet Oncol Haematol. 2009;13(8):556-558.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/ELAVL1ID44237ch19p13.html

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indexed on : Thu Dec 4 15:45:23 CET 2014

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