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RBM5 (RNA binding motif protein 5)

Written2007-02Mirna Mourtada-Maarabouni
School of Life Sciences, Keele University, Keele, Staffs, ST5 5BG, United Kingdom

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)LUCA15
H37
Other aliasLUCA-15
G15
HGNC (Hugo) RBM5
LocusID (NCBI) 10181
Atlas_Id 42069
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 50126341 and ends at 50156397 bp from pter ( according to hg19-Feb_2009)  [Mapping RBM5.png]
Fusion genes
(updated 2016)
DAPK1 (9q21.33) / RBM5 (3p21.31)HACL1 (3p25.1) / RBM5 (3p21.31)NFIX (19p13.2) / RBM5 (3p21.31)
RBM5 (3p21.31) / EPHA6 (3q11.2)
Note 3p21.3 is a putative human lung cancer tumor suppressor region. RBM5/LUCA-15 is a putative tumor suppressor gene

DNA/RNA

 
  RBM5/LUCA-15 splice variants. Boxes represent the exons, intronic sequences are represented by horizontal lines. The arrows point to the STOP codon in the protein coding sequence.
Description The gene spans about 30.03 Kb. Orientation plus strand. At least 25 exons.
Transcription Full length RBM5 has 3.1 Kb, 2448 bp open reading frame. The gene encodes a number of alternative splice variants, identified by reverse transcription polymerase chain reaction. One splice variant lacks exon 6, RBM5delta6. Three other RNA splice variants retain intronic sequences, RBM5+5+6 retains introns 5 and 6, RBM5+6 retains intron 6 and clone 26 which is a partial cDNA containing an open reading frame and terminates within intron 6. A 326 bp antisense cDNA that maps to the intronic region of RBM5, je2, has also been identified. Both, RBM5delta6 and clone 26 cDNAs have been cloned.

Protein

Description Full length RBM5 encodes a protein with a molecular mass of about 90 kDa (815 amino acids). The protein has two RNA Binding Domains (RBD), also recognized as RNA Recognition Motif (RRM). RBM5 structure also features other functional motifs, which includes two putative zinc-finger DNA binding motifs, two bipartite nuclear localisation signals and a G-patch domain (a conserved domain in eukaryotic RNA-processing proteins and type D retroviral polyproteins), suggesting a role for RBM5/LUCA-15 in RNA processing. In addition, the C-terminal region of RBM5/LUCA-15 contains several domains including a glutamine rich domain (362-385), which is thought to serve as protein-protein interaction site in certain RNA- and DNA- binding proteins.
RBM5delta6 encodes a protein of 17 kDa, due to a frameshift mutation caused by the deletion of exon 6. The only functional motif retained by this truncated protein is the arginine/glycine-rich amino terminal region. A putative 21 kDa is reported to be encoded by RBM5+5+6 and clone 26, as revealed by an in vitro transcription/translation study in rabbit reticulocyte lysate.
Expression Full length RBM5 and its alternative splice variants RNA are widely expressed in both primary tissue and cell lines. Northern blot analysis revealed higher expression in skeletal and heart muscles and pancreas. The expression of the full length RBM5 mRNA is reported to be high in adult thymus and low in the foetal thymus, suggesting that its expression is developmentally regulated. Full length RBM5/LUCA-15 is reported to be down-regulated in breast cancer specimens, in 82% of primary non-small-cell lung carcinoma specimens and in many lung cancer cell lines and in vestibular schwannomas (27 fold reduction). The expression of RBM5delta6 RNA is highest in transformed cells. The full length RBM5 protein is ubiquitously expressed in human tissues. It was found to be downregulated in 73% of primary non-small-cell lung carcinoma specimens compared to normal adjacent tissue. RBM5/LUCA-15 was one of the antigens identified by autologous antibody in patients with renal carcinoma. Overexpression of je2, the 326 bp antisense sequence, resulted in the downregulation of the RBM5 protein (95 kDa) and the upregulation of the 17 kDa protein (RBM5delta6).
Localisation RBM5 protein includes bipartite nuclear localisation signals suggesting its localisation to the nucleus.
Function RBM5/LUCA-15 is among the 35 genes located within the 370 kb overlapping lung cancer homozygous deletion region at 3p21.3. RBM5 has been implicated in the control of cell death by apoptosis and cell proliferation. RBM5's involvement in apoptosis and malignancy has been the focus of many recent studies, with all results converging on a role for RBM5/LUCA-15 as a Tumor Suppressor Gene (TSG). RBM5 splice variants have been shown to function as regulators of apoptosis. Stable expression of Je2, in human T-cell lines CEM-C7 and Jurkat produced marked inhibition of Fas-mediated apoptosis and conferred protection from apoptosis induced by other stimuli. RBM5delta6 inhibits CD95-mediated apoptosis as well as accelerating cell proliferation.
Overexpression of the full length RBM5 in CEM-C7 and Jurkat T-cell lines suppressed cell proliferation both by inducing apoptosis and by inducing cell cycle arrest in G1. Consistently, RBM5/LUCA-15 overexpression also inhibited human lung cancer cell growth (A549 non-small cell lung cancer line) by increasing apoptosis and inducing cell cycle arrest in G1. This inhibition of cell growth was reported to be associated with decreased cyclin A and phosphorylated RB and an increase in the level of the proapototic protein Bax. Introducing RBM5/LUCA-15 into breast cancer cells that had 3p21-22 deletions reduced both anchorage-dependent and anchorage-independent growth. RBM5/LUCA-15 also is reported to suppress anchorage-dependent and anchorage-independent growth in A9 mouse fibrosarcoma cells and to inhibit their tumour forming activity in nude mice. RBM5/LUCA-15 was one of the nine genes down-regulated in metastasis and it has been included in the 17 common gene signature associated with metastasis identified in multiple solid tumour types. Solid tumours carrying this gene expression signature had high rates of metastasis and poor clinical outcome. Microarray-based analysis of changes in gene expression caused by the modulation of the level of RBM5/LUCA-15 were carried out. Among 5603 genes on cDNA microarray, 35 genes, well known for their roles in the cell cycle as well as in apoptosis, were found to be differentially expressed as a result of RBM5/LUCA-15 overexpression in CEM-C7 cells.
These RBM5/LUCA-15 modulated genes include a number of cyclin-dependent kinase complexes, most notably CDK2 and three putative oncogenes which are down-regulated by RBM5/LUCA-15. These are Pim-1, a serine/threonine kinase, ITPA (inosine triphosphate pyrophosphatase) and Amplified in Breast cancer 1 (AIB1). Other functionally important genes modulated by RBM5/LUCA-15 are well established to play specific anti apoptotic roles such as BIRC4 (AIP3), BIRC3 (cIAP2, MIHC), Mcl-1, a member of the Bcl-2 family of apoptosis suppressors, and TRAF1, supporting a role for RBM5/LUCA-15 in apoptosis. Other genes upregulated by RBM5/LUCA-15 include Stat5b, Annexin I and Bone Morphogenetic Protein 5 (BMP5), implicated in apoptosis, immunosuppression and organ development respectively.
Homology RBM5 shares 30% amino acid sequence homology with its immediate telomeric neighbor, the putative tumor suppressor gene RBM6. Another RNA Binding Motif protein that shares high homology with RBM5 (53% at the amino acid level) is RBM10. The RBM10 gene is located on the X chromosome at p11.23. No function has yet been determined for RBM10. The mouse RBM5 gene is 90% identical on cDNA level and 97% on protein level. The fly proteome contain three similar proteins, of which CG4887 gene product shows 43% similarity. The rat binding protein S1-1 has similar domain structure and is close in amino acid sequence to RBM5.

Mutations

Note Mutations in the RMB5 gene have not been found in lung cancer. RBM5 is reported to be downregulated in RAS-transformed Rat-1 cells, in samples from breast cancer, in human schwannomas and in about 75% of primary lung cancers specimens. RBM5 was one of the nine genes down-regulated in metastasis in primary tumors and it has been included in the 17 common gene signature associated with metastasis identified in multiple solid tumour types. Solid tumours carrying this gene expression signature had high rates of metastasis and poor clinical outcomes.

Implicated in

Note
  
Entity Lung cancer and many other cancers
Disease RBM5 is located at the human chromosomal locus 3p21.3, which is strongly associated with lung cancer and many other cancers, including head and neck, renal, breast and female genital tract. More than 90% of freshly microdissected primary lung cancers display loss of heterozygosity (LOH) of 3p21.3. RBM5 is implicated in apoptosis and in cell cycle regulation.
Oncogenesis The ability of RBM5/LUCA-15 to inhibit the growth of transformed cells fulfils one of the criteria for a tumor suppressor. The simultaneous changes in proliferation and inhibition of apoptosis brought about by dysregulation of the RBM5/LUCA-15 locus are likely to be of major significance in oncogenesis.
  

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Citation

This paper should be referenced as such :
Mourtada-Maarabouni, M
RBM5 (RNA binding motif protein 5)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):213-216.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RBM5ID42069ch3p21.html


External links

Nomenclature
HGNC (Hugo)RBM5   9902
Cards
AtlasRBM5ID42069ch3p21
Entrez_Gene (NCBI)RBM5  10181  RNA binding motif protein 5
AliasesG15; H37; LUCA15; RMB5
GeneCards (Weizmann)RBM5
Ensembl hg19 (Hinxton)ENSG00000003756 [Gene_View]  chr3:50126341-50156397 [Contig_View]  RBM5 [Vega]
Ensembl hg38 (Hinxton)ENSG00000003756 [Gene_View]  chr3:50126341-50156397 [Contig_View]  RBM5 [Vega]
ICGC DataPortalENSG00000003756
TCGA cBioPortalRBM5
AceView (NCBI)RBM5
Genatlas (Paris)RBM5
WikiGenes10181
SOURCE (Princeton)RBM5
Genetics Home Reference (NIH)RBM5
Genomic and cartography
GoldenPath hg19 (UCSC)RBM5  -     chr3:50126341-50156397 +  3p21.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)RBM5  -     3p21.3   [Description]    (hg38-Dec_2013)
EnsemblRBM5 - 3p21.3 [CytoView hg19]  RBM5 - 3p21.3 [CytoView hg38]
Mapping of homologs : NCBIRBM5 [Mapview hg19]  RBM5 [Mapview hg38]
OMIM606884   
Gene and transcription
Genbank (Entrez)AB208813 AB586690 AF091263 AF103802 AF107493
RefSeq transcript (Entrez)NM_005778
RefSeq genomic (Entrez)NC_000003 NC_018914 NG_030403 NT_022517 NW_004929309
Consensus coding sequences : CCDS (NCBI)RBM5
Cluster EST : UnigeneHs.439480 [ NCBI ]
CGAP (NCI)Hs.439480
Alternative Splicing GalleryENSG00000003756
Gene ExpressionRBM5 [ NCBI-GEO ]   RBM5 [ EBI - ARRAY_EXPRESS ]   RBM5 [ SEEK ]   RBM5 [ MEM ]
Gene Expression Viewer (FireBrowse)RBM5 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10181
GTEX Portal (Tissue expression)RBM5
Protein : pattern, domain, 3D structure
UniProt/SwissProtP52756   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP52756  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP52756
Splice isoforms : SwissVarP52756
PhosPhoSitePlusP52756
Domaine pattern : Prosite (Expaxy)G_PATCH (PS50174)    RRM (PS50102)    ZF_RANBP2_1 (PS01358)    ZF_RANBP2_2 (PS50199)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)G_patch_dom    Nucleotide-bd_a/b_plait    RRM_dom    Znf_C2H2    Znf_C2H2-like    Znf_RanBP2   
Domain families : Pfam (Sanger)G-patch (PF01585)    zf-RanBP (PF00641)   
Domain families : Pfam (NCBI)pfam01585    pfam00641   
Domain families : Smart (EMBL)G_patch (SM00443)  RRM (SM00360)  ZnF_C2H2 (SM00355)  ZnF_RBZ (SM00547)  
Conserved Domain (NCBI)RBM5
DMDM Disease mutations10181
Blocks (Seattle)RBM5
PDB (SRS)2LK0    2LK1    2LKZ   
PDB (PDBSum)2LK0    2LK1    2LKZ   
PDB (IMB)2LK0    2LK1    2LKZ   
PDB (RSDB)2LK0    2LK1    2LKZ   
Structural Biology KnowledgeBase2LK0    2LK1    2LKZ   
SCOP (Structural Classification of Proteins)2LK0    2LK1    2LKZ   
CATH (Classification of proteins structures)2LK0    2LK1    2LKZ   
SuperfamilyP52756
Human Protein AtlasENSG00000003756
Peptide AtlasP52756
HPRD06052
IPIIPI00005036   IPI00796867   IPI00930619   IPI00927051   IPI00930333   IPI01013720   IPI01013343   IPI00952868   IPI00926920   IPI00926674   IPI01018697   IPI00926331   IPI00926115   
Protein Interaction databases
DIP (DOE-UCLA)P52756
IntAct (EBI)P52756
FunCoupENSG00000003756
BioGRIDRBM5
STRING (EMBL)RBM5
ZODIACRBM5
Ontologies - Pathways
QuickGOP52756
Ontology : AmiGOnucleotide binding  spliceosomal complex assembly  regulation of alternative mRNA splicing, via spliceosome  mRNA splicing, via spliceosome  DNA binding  RNA binding  mRNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  spliceosomal complex  RNA processing  apoptotic process  zinc ion binding  negative regulation of cell proliferation  positive regulation of apoptotic process  positive regulation of apoptotic process  poly(A) RNA binding  
Ontology : EGO-EBInucleotide binding  spliceosomal complex assembly  regulation of alternative mRNA splicing, via spliceosome  mRNA splicing, via spliceosome  DNA binding  RNA binding  mRNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  spliceosomal complex  RNA processing  apoptotic process  zinc ion binding  negative regulation of cell proliferation  positive regulation of apoptotic process  positive regulation of apoptotic process  poly(A) RNA binding  
REACTOMEP52756 [protein]
REACTOME Pathways72163 [pathway]   
NDEx NetworkRBM5
Atlas of Cancer Signalling NetworkRBM5
Wikipedia pathwaysRBM5
Orthology - Evolution
OrthoDB10181
GeneTree (enSembl)ENSG00000003756
Phylogenetic Trees/Animal Genes : TreeFamRBM5
HOVERGENP52756
HOGENOMP52756
Homologs : HomoloGeneRBM5
Homology/Alignments : Family Browser (UCSC)RBM5
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRBM5 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RBM5
dbVarRBM5
ClinVarRBM5
1000_GenomesRBM5 
Exome Variant ServerRBM5
ExAC (Exome Aggregation Consortium)RBM5 (select the gene name)
Genetic variants : HAPMAP10181
Genomic Variants (DGV)RBM5 [DGVbeta]
DECIPHER (Syndromes)3:50126341-50156397  ENSG00000003756
CONAN: Copy Number AnalysisRBM5 
Mutations
ICGC Data PortalRBM5 
TCGA Data PortalRBM5 
Broad Tumor PortalRBM5
OASIS PortalRBM5 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRBM5  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDRBM5
intOGen PortalRBM5
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
BioMutasearch RBM5
DgiDB (Drug Gene Interaction Database)RBM5
DoCM (Curated mutations)RBM5 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RBM5 (select a term)
intoGenRBM5
NCG5 (London)RBM5
Cancer3DRBM5(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM606884   
Orphanet
MedgenRBM5
Genetic Testing Registry RBM5
NextProtP52756 [Medical]
TSGene10181
GENETestsRBM5
Huge Navigator RBM5 [HugePedia]
snp3D : Map Gene to Disease10181
BioCentury BCIQRBM5
ClinGenRBM5
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10181
Chemical/Pharm GKB GenePA34267
Clinical trialRBM5
Miscellaneous
canSAR (ICR)RBM5 (select the gene name)
Probes
Litterature
PubMed62 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRBM5
EVEXRBM5
GoPubMedRBM5
iHOPRBM5
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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