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)


Alias (NCBI)MGC10823
HGNC Alias symbMaxp1
HGNC Alias namenovel Ras effector 1
 regulator for cell adhesion and polarization enriched in lymphoid tissues
HGNC Previous nameRas association (RalGDS/AF-6) domain family member 5
LocusID (NCBI) 83593
Atlas_Id 42059
Location 1q32.1  [Link to chromosome band 1q32]
Location_base_pair Starts at 206557164 and ends at 206589447 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping RASSF5.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)
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.


  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.


  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.


Note No tumor mutations yet reported.

Implicated in

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.


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


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 ]

External links


HGNC (Hugo)RASSF5   17609
Entrez_Gene (NCBI)RASSF5    Ras association domain family member 5
AliasesMaxp1; NORE1; NORE1A; NORE1B; 
GeneCards (Weizmann)RASSF5
Ensembl hg19 (Hinxton)ENSG00000266094 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000266094 [Gene_View]  ENSG00000266094 [Sequence]  chr1:206557164-206589447 [Contig_View]  RASSF5 [Vega]
ICGC DataPortalENSG00000266094
Genatlas (Paris)RASSF5
SOURCE (Princeton)RASSF5
Genetics Home Reference (NIH)RASSF5
Genomic and cartography
GoldenPath hg38 (UCSC)RASSF5  -     chr1:206557164-206589447 +  1q32.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RASSF5  -     1q32.1   [Description]    (hg19-Feb_2009)
GoldenPathRASSF5 - 1q32.1 [CytoView hg19]  RASSF5 - 1q32.1 [CytoView hg38]
Genome Data Viewer NCBIRASSF5 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB209145 AF445801 AK056568 AK074115 AK289861
RefSeq transcript (Entrez)NM_031437 NM_182663 NM_182664 NM_182665
Consensus coding sequences : CCDS (NCBI)RASSF5
Gene ExpressionRASSF5 [ NCBI-GEO ]   RASSF5 [ EBI - ARRAY_EXPRESS ]   RASSF5 [ SEEK ]   RASSF5 [ MEM ]
Gene Expression Viewer (FireBrowse)RASSF5 [ Firebrowse - Broad ]
GenevisibleExpression of RASSF5 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)83593
GTEX Portal (Tissue expression)RASSF5
Human Protein AtlasENSG00000266094-RASSF5 [pathology]   [cell]   [tissue]
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
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-like_domsf   
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
PDB (RSDB)4LGD    4OH8   
PDB Europe4LGD    4OH8   
PDB (PDBSum)4LGD    4OH8   
PDB (IMB)4LGD    4OH8   
Structural Biology KnowledgeBase4LGD    4OH8   
SCOP (Structural Classification of Proteins)4LGD    4OH8   
CATH (Classification of proteins structures)4LGD    4OH8   
AlphaFold pdb e-kbQ8WWW0   
Human Protein Atlas [tissue]ENSG00000266094-RASSF5 [tissue]
Protein Interaction databases
IntAct (EBI)Q8WWW0
Ontologies - Pathways
Ontology : AmiGOprotein binding  nucleus  cytoplasm  microtubule  apoptotic process  signal transduction  negative regulation of cell population proliferation  small 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  signal transduction  negative regulation of cell population proliferation  small 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
GeneTree (enSembl)ENSG00000266094
Phylogenetic Trees/Animal Genes : TreeFamRASSF5
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]  
Fusion : QuiverRASSF5
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRASSF5 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RASSF5
Exome Variant ServerRASSF5
GNOMAD BrowserENSG00000266094
Varsome BrowserRASSF5
ACMGRASSF5 variants
Genomic Variants (DGV)RASSF5 [DGVbeta]
DECIPHERRASSF5 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRASSF5 
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]  
Somatic Mutations in Cancer : COSMIC3DRASSF5
Mutations and Diseases : HGMDRASSF5
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)RASSF5
DoCM (Curated mutations)RASSF5
CIViC (Clinical Interpretations of Variants in Cancer)RASSF5
NCG (London)RASSF5
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry RASSF5
NextProtQ8WWW0 [Medical]
Target ValidationRASSF5
Huge Navigator RASSF5 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDRASSF5
Pharm GKB GenePA134958571
Clinical trialRASSF5
DataMed IndexRASSF5
PubMed78 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
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 Oct 8 21:26:41 CEST 2021

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

For comments and suggestions or contributions, please contact us