Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

RASSF5 (Ras association (RalGDS/AF-6) domain family member 5)

Written2011-10Lee Schmidt, Geoffrey J Clark
University of Louisville, Room 119C, Baxter II Research Building, 580 S Preston Street, Louisville, KY 40202, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesRas association (RalGDS/AF-6) domain family member 5
Alias_symbol (synonym)Maxp1
NORE1
RAPL
Other aliasMGC10823
MGC17344
NORE1A
NORE1B
RASSF3
HGNC (Hugo) RASSF5
LocusID (NCBI) 83593
Atlas_Id 42059
Location 1q32.1  [Link to chromosome band 1q32]
Location_base_pair Starts at 206507530 and ends at 206589284 bp from pter ( according to hg19-Feb_2009)  [Mapping RASSF5.png]
 
Fusion genes
(updated 2016)
HNRNPL (19q13.2) / RASSF5 (1q32.1)MAPKAPK2 (1q32.1) / RASSF5 (1q32.1)RASSF5 (1q32.1) / IKBKE (1q32.1)
RASSF5 (1q32.1) / LSAMP (3q13.31)RASSF5 (1q32.1) / RASSF5 (1q32.1)TIMM17A (1q32.1) / RASSF5 (1q32.1)
Note Murine RASSF5 originally named Nore1a. Nore1B independently identified and designated RAPL. Rat RASSF5 also cloned independently and designated Maxp1.

DNA/RNA

 
  Figure 1. Isoform A is shown as the longest isoform with 6 exons. Isoform B, without an alternate exon, shows that the frameshift gives a shortened and unique C-terminus. Isoform C is shown with a special 5' UTR and lacks an in-frame coding region leading to a unique N-terminus. The total coding sequence for Isoform A is about 1260 bases with the other isoforms being smaller.
Description The human gene for RASSF5 is 81 kb in length and is located on chromosome 1(q32.1). The gene can produce 4 protein isoforms, two via differential exon usage, a third via differential promoter usage and the genesis of the 4th (which can be found as an EST clone) is not yet clear. The largest isoform, A, is 418 amino acids long and has a molecular weight of about 47 kD. The protein structure of RASSF5A contains a proline-rich region at the N-terminus which contains potential SH3 binding sites and a nuclear localization signal. This is followed by a cystein rich domain, sometimes referred to as a zinc finger. Next is the Ras association domain and this is followed by sequence containing the SARAH motif required for binding to the pro-apoptotic kinases MST1 and MST2. A second nuclear localization sequence has been reported between amino acids 200-260 and a nuclear export sequence between amino acids 260-300.

Protein

 
  Figure 2. A figure showing the processed mRNA as well as the amino acid sequence for isoforms A-D followed by motif explanation of isoform A (Nore1a).
Description The full length cDNA (for isoform A) encodes for a 47-kDa protein which contains a proline-rich region at the N-terminus followed by a putative diacylglycerol/phorbol ester binding domain. This is followed by the Ras association (RA) domain and then the domain containing a SARAH motif. This later is responsible for binding to the pro-apoptotic kinases MST1 and MST2.
Expression Nore1a mRNA is expressed in the lung, kidney, liver, brain, spleen, thymus and heart.
Localisation It can be detected on microtubules, in the centrosome, but appears most obvious in the nucleus.
Function RASSF5A is a pro-apoptotic Ras effector that can bind and relocalize the pro-apoptotic MST kinases in the presence of activated Ras. It can also promote cell cycle arrest and modulate the activity of p53 by regulating its' nuclear localization. Knockdown of RASSF5A promotes cellular proliferation and soft agar growth. Thus, RASSF5A appears to function as a Ras regulated tumor suppressor. Analysis of human tumors has found little evidence of somatic mutation but the gene is frequently inactivated by promoter methylation in a broad range of human tumors. RASSF5C (also known as Nore1b or RAPL) has been reported to modulate cellular adhesion and to be regulated by the Ras related protein Rap1a. RASSF5C has also been implicated as serving as an adaptor protein to facilitate the interaction of Ras and CARMA1.

Mutations

Note No tumor mutations yet reported.

Implicated in

Note
  
Entity Clear cell renal carcinoma
Note RASSF5 is frequently down-regulated by promoter methylation in a variety of tumors including clear cell renal carcinomas. Moreover, a rare hereditary form of kidney cancer has been reported that maps with a translocation inactivating the RASSF5 gene.
  
  
Entity Various cancers
Note Nore1a is frequently inactivated by promoter methylation in renal carcinoma, breast cancer, lung cancer, liver cancer and neurological tumors.
  

Bibliography

Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases.
Aoyama Y, Avruch J, Zhang XF.
Oncogene. 2004 Apr 22;23(19):3426-33.
PMID 15007383
 
Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases.
Avruch J, Praskova M, Ortiz-Vega S, Liu M, Zhang XF.
Methods Enzymol. 2006;407:290-310.
PMID 16757333
 
Growth and tumor suppressor NORE1A is a regulatory node between Ras signaling and microtubule nucleation.
Bee C, Moshnikova A, Mellor CD, Molloy JE, Koryakina Y, Stieglitz B, Khokhlatchev A, Herrmann C.
J Biol Chem. 2010 May 21;285(21):16258-66. Epub 2010 Mar 25.
PMID 20339001
 
NORE1A tumor suppressor candidate modulates p21CIP1 via p53.
Calvisi DF, Donninger H, Vos MD, Birrer MJ, Gordon L, Leaner V, Clark GJ.
Cancer Res. 2009 Jun 1;69(11):4629-37. Epub 2009 May 12.
PMID 19435914
 
The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell renal cell carcinomas.
Chen J, Lui WO, Vos MD, Clark GJ, Takahashi M, Schoumans J, Khoo SK, Petillo D, Lavery T, Sugimura J, Astuti D, Zhang C, Kagawa S, Maher ER, Larsson C, Alberts AS, Kanayama HO, Teh BT.
Cancer Cell. 2003 Nov;4(5):405-13.
PMID 14667507
 
The RASSF1A tumor suppressor.
Donninger H, Vos MD, Clark GJ.
J Cell Sci. 2007 Sep 15;120(Pt 18):3163-72. (REVIEW)
PMID 17878233
 
NORE1A, a homologue of RASSF1A tumour suppressor gene is inactivated in human cancers.
Hesson L, Dallol A, Minna JD, Maher ER, Latif F.
Oncogene. 2003 Feb 13;22(6):947-54.
PMID 12584574
 
Identification of a novel Ras-regulated proapoptotic pathway.
Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J.
Curr Biol. 2002 Feb 19;12(4):253-65.
PMID 11864565
 
Functional interaction of the Ras effector RASSF5 with the tyrosine kinase Lck: critical role in nucleocytoplasmic transport and cell cycle regulation.
Kumari G, Singhal PK, Suryaraja R, Mahalingam S.
J Mol Biol. 2010 Mar 19;397(1):89-109. Epub 2010 Jan 11.
PMID 20064523
 
Death pathways triggered by activated Ras in cancer cells.
Overmeyer JH, Maltese WA.
Front Biosci. 2011 Jan 1;16:1693-713. (REVIEW)
PMID 21196257
 
Tumor suppressor ras association domain family 5 (RASSF5/NORE1) mediates death receptor ligand-induced apoptosis.
Park J, Kang SI, Lee SY, Zhang XF, Kim MS, Beers LF, Lim DS, Avruch J, Kim HS, Lee SB.
J Biol Chem. 2010 Nov 5;285(45):35029-38. Epub 2010 Sep 1.
PMID 20810663
 
Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras.
Praskova M, Khoklatchev A, Ortiz-Vega S, Avruch J.
Biochem J. 2004 Jul 15;381(Pt 2):453-62.
PMID 15109305
 
The RASSF proteins in cancer; from epigenetic silencing to functional characterization.
Richter AM, Pfeifer GP, Dammann RH.
Biochim Biophys Acta. 2009 Dec;1796(2):114-28. Epub 2009 Mar 31. (REVIEW)
PMID 19344752
 
Identification of Nore1 as a potential Ras effector.
Vavvas D, Li X, Avruch J, Zhang XF.
J Biol Chem. 1998 Mar 6;273(10):5439-42.
PMID 9488663
 
The pro-apoptotic Ras effector Nore1 may serve as a Ras-regulated tumor suppressor in the lung.
Vos MD, Martinez A, Ellis CA, Vallecorsa T, Clark GJ.
J Biol Chem. 2003 Jun 13;278(24):21938-43. Epub 2003 Apr 3.
PMID 12676952
 

Citation

This paper should be referenced as such :
Schmidt, L ; Clark, GJ
RASSF5 (Ras association (RalGDS/AF-6) domain family member 5)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(3):212-215.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RASSF5ID42059ch1q32.html


External links

Nomenclature
HGNC (Hugo)RASSF5   17609
Cards
AtlasRASSF5ID42059ch1q32
Entrez_Gene (NCBI)RASSF5  83593  Ras association domain family member 5
AliasesMaxp1; NORE1; NORE1A; NORE1B; 
RAPL; RASSF3
GeneCards (Weizmann)RASSF5
Ensembl hg19 (Hinxton)ENSG00000266094 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000266094 [Gene_View]  chr1:206507530-206589284 [Contig_View]  RASSF5 [Vega]
ICGC DataPortalENSG00000266094
TCGA cBioPortalRASSF5
AceView (NCBI)RASSF5
Genatlas (Paris)RASSF5
WikiGenes83593
SOURCE (Princeton)RASSF5
Genetics Home Reference (NIH)RASSF5
Genomic and cartography
GoldenPath hg38 (UCSC)RASSF5  -     chr1:206507530-206589284 +  1q32.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RASSF5  -     1q32.1   [Description]    (hg19-Feb_2009)
EnsemblRASSF5 - 1q32.1 [CytoView hg19]  RASSF5 - 1q32.1 [CytoView hg38]
Mapping of homologs : NCBIRASSF5 [Mapview hg19]  RASSF5 [Mapview hg38]
OMIM607020   
Gene and transcription
Genbank (Entrez)AB209145 AF445801 AK056568 AK074115 AK289861
RefSeq transcript (Entrez)NM_031437 NM_182663 NM_182664 NM_182665
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RASSF5
Cluster EST : UnigeneHs.497579 [ NCBI ]
CGAP (NCI)Hs.497579
Alternative Splicing GalleryENSG00000266094
Gene ExpressionRASSF5 [ NCBI-GEO ]   RASSF5 [ EBI - ARRAY_EXPRESS ]   RASSF5 [ SEEK ]   RASSF5 [ MEM ]
Gene Expression Viewer (FireBrowse)RASSF5 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)83593
GTEX Portal (Tissue expression)RASSF5
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8WWW0   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8WWW0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8WWW0
Splice isoforms : SwissVarQ8WWW0
PhosPhoSitePlusQ8WWW0
Domaine pattern : Prosite (Expaxy)RA (PS50200)    SARAH (PS50951)    ZF_DAG_PE_1 (PS00479)    ZF_DAG_PE_2 (PS50081)   
Domains : Interpro (EBI)C-RASSF    PE/DAG-bd    RA_dom    RASSF5    SARAH_dom    Ubiquitin-rel_dom   
Domain families : Pfam (Sanger)C1_1 (PF00130)    Nore1-SARAH (PF16517)    RA (PF00788)   
Domain families : Pfam (NCBI)pfam00130    pfam16517    pfam00788   
Domain families : Smart (EMBL)C1 (SM00109)  RA (SM00314)  
Conserved Domain (NCBI)RASSF5
DMDM Disease mutations83593
Blocks (Seattle)RASSF5
PDB (SRS)4LGD    4OH8   
PDB (PDBSum)4LGD    4OH8   
PDB (IMB)4LGD    4OH8   
PDB (RSDB)4LGD    4OH8   
Structural Biology KnowledgeBase4LGD    4OH8   
SCOP (Structural Classification of Proteins)4LGD    4OH8   
CATH (Classification of proteins structures)4LGD    4OH8   
SuperfamilyQ8WWW0
Human Protein AtlasENSG00000266094
Peptide AtlasQ8WWW0
HPRD06117
IPIIPI00332633   IPI00103528   IPI00179101   IPI00183637   IPI00383066   
Protein Interaction databases
DIP (DOE-UCLA)Q8WWW0
IntAct (EBI)Q8WWW0
FunCoupENSG00000266094
BioGRIDRASSF5
STRING (EMBL)RASSF5
ZODIACRASSF5
Ontologies - Pathways
QuickGOQ8WWW0
Ontology : AmiGOprotein binding  nucleus  cytoplasm  microtubule  apoptotic process  negative regulation of cell proliferation  Ras GTPase binding  positive regulation of protein ubiquitination  intracellular signal transduction  regulation of apoptotic process  metal ion binding  regulation of protein localization to nucleus  
Ontology : EGO-EBIprotein binding  nucleus  cytoplasm  microtubule  apoptotic process  negative regulation of cell proliferation  Ras GTPase binding  positive regulation of protein ubiquitination  intracellular signal transduction  regulation of apoptotic process  metal ion binding  regulation of protein localization to nucleus  
Pathways : KEGGRas signaling pathway    Rap1 signaling pathway    Leukocyte transendothelial migration    Pathways in cancer    Non-small cell lung cancer   
NDEx NetworkRASSF5
Atlas of Cancer Signalling NetworkRASSF5
Wikipedia pathwaysRASSF5
Orthology - Evolution
OrthoDB83593
GeneTree (enSembl)ENSG00000266094
Phylogenetic Trees/Animal Genes : TreeFamRASSF5
HOVERGENQ8WWW0
HOGENOMQ8WWW0
Homologs : HomoloGeneRASSF5
Homology/Alignments : Family Browser (UCSC)RASSF5
Gene fusions - Rearrangements
Fusion : MitelmanRASSF5/IKBKE [1q32.1/1q32.1]  
Fusion : MitelmanTIMM17A/RASSF5 [1q32.1/1q32.1]  [t(1;1)(q32;q32)]  
Fusion: TCGARASSF5 1q32.1 IKBKE 1q32.1 HNSC
Fusion: TCGATIMM17A 1q32.1 RASSF5 1q32.1 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRASSF5 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RASSF5
dbVarRASSF5
ClinVarRASSF5
1000_GenomesRASSF5 
Exome Variant ServerRASSF5
ExAC (Exome Aggregation Consortium)RASSF5 (select the gene name)
Genetic variants : HAPMAP83593
Genomic Variants (DGV)RASSF5 [DGVbeta]
DECIPHERRASSF5 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRASSF5 
Mutations
ICGC Data PortalRASSF5 
TCGA Data PortalRASSF5 
Broad Tumor PortalRASSF5
OASIS PortalRASSF5 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRASSF5  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDRASSF5
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 RASSF5
DgiDB (Drug Gene Interaction Database)RASSF5
DoCM (Curated mutations)RASSF5 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RASSF5 (select a term)
intoGenRASSF5
NCG5 (London)RASSF5
Cancer3DRASSF5(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM607020   
Orphanet
MedgenRASSF5
Genetic Testing Registry RASSF5
NextProtQ8WWW0 [Medical]
TSGene83593
GENETestsRASSF5
Target ValidationRASSF5
Huge Navigator RASSF5 [HugePedia]
snp3D : Map Gene to Disease83593
BioCentury BCIQRASSF5
ClinGenRASSF5
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD83593
Chemical/Pharm GKB GenePA134958571
Clinical trialRASSF5
Miscellaneous
canSAR (ICR)RASSF5 (select the gene name)
Probes
Litterature
PubMed67 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRASSF5
EVEXRASSF5
GoPubMedRASSF5
iHOPRASSF5
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Jun 30 11:16:40 CEST 2017

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.