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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)


Alias (NCBI)LUCA-15
HGNC (Hugo) RBM5
HGNC Alias symbLUCA15
LocusID (NCBI) 10181
Atlas_Id 42069
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 50088919 and ends at 50119021 bp from pter ( according to hg19-Feb_2009)  [Mapping RBM5.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
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


  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.


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.


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

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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Candidate tumor suppressor LUCA-15/RBM5/H37 modulates expression of apoptosis and cell cycle genes.
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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 :

External links

HGNC (Hugo)RBM5   9902
Entrez_Gene (NCBI)RBM5  10181  RNA binding motif protein 5
AliasesG15; H37; LUCA-15; LUCA15; 
GeneCards (Weizmann)RBM5
Ensembl hg19 (Hinxton)ENSG00000003756 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000003756 [Gene_View]  ENSG00000003756 [Sequence]  chr3:50088919-50119021 [Contig_View]  RBM5 [Vega]
ICGC DataPortalENSG00000003756
TCGA cBioPortalRBM5
AceView (NCBI)RBM5
Genatlas (Paris)RBM5
SOURCE (Princeton)RBM5
Genetics Home Reference (NIH)RBM5
Genomic and cartography
GoldenPath hg38 (UCSC)RBM5  -     chr3:50088919-50119021 +  3p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RBM5  -     3p21.31   [Description]    (hg19-Feb_2009)
GoldenPathRBM5 - 3p21.31 [CytoView hg19]  RBM5 - 3p21.31 [CytoView hg38]
genome Data Viewer NCBIRBM5 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB208813 AB586690 AF091263 AF103802 AF107493
RefSeq transcript (Entrez)NM_005778
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RBM5
Alternative Splicing GalleryENSG00000003756
Gene ExpressionRBM5 [ NCBI-GEO ]   RBM5 [ EBI - ARRAY_EXPRESS ]   RBM5 [ SEEK ]   RBM5 [ MEM ]
Gene Expression Viewer (FireBrowse)RBM5 [ Firebrowse - Broad ]
GenevisibleExpression of RBM5 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10181
GTEX Portal (Tissue expression)RBM5
Human Protein AtlasENSG00000003756-RBM5 [pathology]   [cell]   [tissue]
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
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_sf    OCRE    RBD_domain_sf    RBM5    RBM5_RRM1    RBM5_RRM2    RRM_dom    Znf_C2H2_type    Znf_RanBP2    Znf_RanBP2_sf   
Domain families : Pfam (Sanger)G-patch (PF01585)    OCRE (PF17780)    RRM_1 (PF00076)    zf-RanBP (PF00641)   
Domain families : Pfam (NCBI)pfam01585    pfam17780    pfam00076    pfam00641   
Domain families : Smart (EMBL)G_patch (SM00443)  RRM (SM00360)  ZnF_RBZ (SM00547)  
Conserved Domain (NCBI)RBM5
DMDM Disease mutations10181
Blocks (Seattle)RBM5
PDB (RSDB)2LK0    2LK1    2LKZ    5MF9    5MFY   
PDB Europe2LK0    2LK1    2LKZ    5MF9    5MFY   
PDB (PDBSum)2LK0    2LK1    2LKZ    5MF9    5MFY   
PDB (IMB)2LK0    2LK1    2LKZ    5MF9    5MFY   
Structural Biology KnowledgeBase2LK0    2LK1    2LKZ    5MF9    5MFY   
SCOP (Structural Classification of Proteins)2LK0    2LK1    2LKZ    5MF9    5MFY   
CATH (Classification of proteins structures)2LK0    2LK1    2LKZ    5MF9    5MFY   
Human Protein Atlas [tissue]ENSG00000003756-RBM5 [tissue]
Peptide AtlasP52756
IPIIPI00005036   IPI00796867   IPI00930619   IPI00927051   IPI00930333   IPI01013720   IPI01013343   IPI00952868   IPI00926920   IPI00926674   IPI01018697   IPI00926331   IPI00926115   
Protein Interaction databases
IntAct (EBI)P52756
Ontologies - Pathways
Ontology : AmiGOspliceosomal complex assembly  regulation of alternative mRNA splicing, via spliceosome  mRNA splicing, via spliceosome  mRNA splicing, via spliceosome  DNA binding  RNA binding  RNA binding  mRNA binding  protein binding  nucleus  nucleus  nucleoplasm  nucleoplasm  spliceosomal complex  RNA processing  apoptotic process  negative regulation of cell proliferation  positive regulation of apoptotic process  positive regulation of apoptotic process  metal ion binding  
Ontology : EGO-EBIspliceosomal complex assembly  regulation of alternative mRNA splicing, via spliceosome  mRNA splicing, via spliceosome  mRNA splicing, via spliceosome  DNA binding  RNA binding  RNA binding  mRNA binding  protein binding  nucleus  nucleus  nucleoplasm  nucleoplasm  spliceosomal complex  RNA processing  apoptotic process  negative regulation of cell proliferation  positive regulation of apoptotic process  positive regulation of apoptotic process  metal ion binding  
REACTOMEP52756 [protein]
REACTOME PathwaysR-HSA-72163 [pathway]   
NDEx NetworkRBM5
Atlas of Cancer Signalling NetworkRBM5
Wikipedia pathwaysRBM5
Orthology - Evolution
GeneTree (enSembl)ENSG00000003756
Phylogenetic Trees/Animal Genes : TreeFamRBM5
Homologs : HomoloGeneRBM5
Homology/Alignments : Family Browser (UCSC)RBM5
Gene fusions - Rearrangements
Fusion : Fusion_HubARCN1--RBM5    CAMK2A--RBM5    CAND1--RBM5    CCDC84--RBM5    CCZ1B--RBM5    CD9--RBM5    CSTF3--RBM5    DAPK1--RBM5    DERL3--RBM5    FKBP11--RBM5    GBE1--RBM5    GBF1--RBM5    GNL3--RBM5    HACL1--RBM5    HIP1--RBM5   
HYAL2--RBM5    IFRD2--RBM5    LYZ--RBM5    MCM3AP--RBM5    NFIX--RBM5    NKTR--RBM5    NOTCH3--RBM5    OSBPL2--RBM5    PDCD5--RBM5    PIM2--RBM5    RBBP7--RBM5    RBM5--ALPL    RBM5--ANO10    RBM5--CTTN    RBM5--CYB561D2   
RBM5--ECE1    RBM5--EPHA6    RBM5--GALNT8    RBM5--GCFC2    RBM5--GTF3C1    RBM5--HNRNPU    RBM5--KCTD20    RBM5--MPND    RBM5--N4BP2L2    RBM5--NDUFA6    RBM5--OPTN    RBM5--PDSS1    RBM5--PLA2G4F    RBM5--POLDIP3    RBM5--QRICH1   
RBM5--RANGAP1    RBM5--RBM6    RBM5--RBPJL    RBM5--RFT1    RBM5--RHOA    RBM5--RNPC3    RBM5--SCAP    RBM5--SGTA    RBM5--SMG6    RBM5--SRSF4    RBM5--THUMPD3    RBM5--TNKS2    RBM5--VIM    RBM5--YARS    RBM5--YTHDF2   
RBM6--RBM5    RPL21--RBM5    SORBS1--RBM5    USP25--RBM5    ZNF276--RBM5   
Fusion : QuiverRBM5
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRBM5 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RBM5
Exome Variant ServerRBM5
GNOMAD BrowserENSG00000003756
Varsome BrowserRBM5
Genetic variants : HAPMAP10181
Genomic Variants (DGV)RBM5 [DGVbeta]
DECIPHERRBM5 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRBM5 
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]  
Somatic Mutations in Cancer : COSMIC3DRBM5
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)
NCG6 (London) select RBM5
Cancer3DRBM5(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry RBM5
NextProtP52756 [Medical]
Target ValidationRBM5
Huge Navigator RBM5 [HugePedia]
snp3D : Map Gene to Disease10181
BioCentury BCIQRBM5
Clinical trials, drugs, therapy
Protein Interactions : CTD10181
Pharm GKB GenePA34267
Clinical trialRBM5
canSAR (ICR)RBM5 (select the gene name)
DataMed IndexRBM5
PubMed83 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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