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RASSF1 (Ras association (RalGDS/AF-6) domain family member)

Written2001-12Debora Angeloni, Michael I. Lerman
Laboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research Facility Bldg. 560 Rm. 12 26 Frederick, MD 21702, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesRas association (RalGDS/AF-6) domain family member 1
Alias_symbol (synonym)NORE2A
REH3P21
RDA32
123F2
Other alias
HGNC (Hugo) RASSF1
LocusID (NCBI) 11186
Atlas_Id 377
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 50367217 and ends at 50378367 bp from pter ( according to hg19-Feb_2009)  [Mapping RASSF1.png]
Local_order telomeric to BLU and centromeric to FUS1
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)
RASSF1 (3p21.31) / CAPN1 (11q13.1)RASSF1 (3p21.31) / PDZRN3 (3p13)
Note RASSF1 is also known as NORE2A. More correctly, NORE must be considered a paralog of RASSF1, a human ortholog of mouse NoreA.
genomic clones: cosmid LUCA 12 and LUCA 13

DNA/RNA

 
  Grey: exon 1a, green: exon 1b; blue: exon 2ab; yellow : exon 2g; brown: exons 3,4, 5, 6. Arrows: transcription start sites. CpG: location of CpG islands. RASSF1A and RASSF1B start with exon 1a and 1b respectively. The second exon (2ab) is common to both forms. Exon 2g is the first exon of RASSF1C and is present in this transcript only.
Description the genomic size of the gene is about 7.6 kb.
Transcription At least three alternative transcripts were identified (A, B and C) that originate from alternative splicing and promoter usage. Exons 3 to 6 are common to all forms. Transcript A has two 5' exons (designated 1a and 2ab), this cDNA is 1,873 bp (ORF: 340 amino acids). RASSF1B first exon is designated 1b and is different from RASSF1A. Exon two is 2ab as in transcript A. cDNA size: 1,664 bp. Transcript RASSF1C first exon is designated 2g, cDNA size 1700 bp (ORF 270 amino acids).
Pseudogene no known pseudogenes.

Protein

 
  Schematic representation of RASSF1 protein variants, as deduced from the transcripts.
Description The carboxy terminus of RASSF1A shows about 55% identity to the mouse protein Nore1 and the rat protein Maxp1, both are Ras effector proteins (Nore1 was shown to interact in vivo with Ras upon receptor activation in a GTP-dependent manner). RASSF1A N terminus has high homology with a domain known as protein kinase C conserved region 1 domain (a cysteine-rich diacylglycerol/phorbol ester binding domain). RASSF1B most likely is constituted only of the Ras association domain.
Expression RASSF1A and RASSF1C are expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, small intestine, colon, peripheral blood leukocytes. RASSF1B is expressed predominantly in cells of hematopoietic origin.
Localisation not determined.
Function RASSF1 binds Ras in a GTP-dependent manner and may serve as the effector that mediates Ras apoptotic effects. Alternatively, it may sequester RAS proteins thereby regulating the availability of these proteins for signaling.

Mutations

Note single nucleotide polymorphism (SNP) in exon 1a: AAG (Lys21)/CAG (Gln21).
Somatic Mutations were rarely found. In non small cell lung cancer four were found: GAC (Asp129) to GAG (Glu129); ATT (Ile135) to ACT (Thr135); CGG (Arg257) to CAG (Gln257); GCC (Ala336) to ACC (Thr336).

Implicated in

Note
  
Entity clear cell renal carcinoma and papillary renal carcinoma; lung cancer; ovarian cancer; prostate cancer, gastric adenocarcinoma; bladder carcinoma; nasopharingeal carcinoma; breast cancer.
Note The mechanism of inactivation of this tumor suppressor consists in promoter hypermethylation. The gene promoter was found hypermetylated in 90 % of primary kidney tumors and 40 % of lung tumors. Hypermethylation and loss of transcription were causally related. Hypermethylation occurs in variable percentage in other tumors and indicate a role for this gene in malignant progression (62 % of bladder carcinoma; 49 % of breast tumors; 40 % of ovarian tumors; 12 % of colon cancer).
  

Bibliography

Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours.
Agathanggelou A, Honorio S, Macartney DP, Martinez A, Dallol A, Rader J, Fullwood P, Chauhan A, Walker R, Shaw JA, Hosoe S, Lerman MI, Minna JD, Maher ER, Latif F
Oncogene. 2001 ; 20 (12) : 1509-1518.
PMID 11313894
 
Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression.
Burbee DG, Forgacs E, Zöchbauer-Müller S, Shivakumar L, Fong K, Gao B, Randle D, Kondo M, Virmani A, Bader S, Sekido Y, Latif F, Milchgrub S, Toyooka S, Gazdar AF, Lerman MI, Zabarovsky E, White M, Minna JD
Journal of the National Cancer Institute. 2001 ; 93 (9) : 691-699.
PMID 11333291
 
Frequent epigenetic inactivation of RASSF1A by aberrant promoter hypermethylation in human gastric adenocarcinoma.
Byun DS, Lee MG, Chae KS, Ryu BG, Chi SG
Cancer research. 2001 ; 61 (19) : 7034-7038.
PMID 11585730
 
Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3.
Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP
Nature genetics. 2000 ; 25 (3) : 315-319.
PMID 10888881
 
The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas.
Dammann R, Takahashi T, Pfeifer GP
Oncogene. 2001 ; 20 (27) : 3563-3567.
PMID 11429703
 
Hypermethylation of the cpG island of Ras association domain family 1A (RASSF1A), a putative tumor suppressor gene from the 3p21.3 locus, occurs in a large percentage of human breast cancers.
Dammann R, Yang G, Pfeifer GP
Cancer research. 2001 ; 61 (7) : 3105-3109.
PMID 11306494
 
The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis.
Dreijerink K, Braga E, Kuzmin I, Geil L, Duh FM, Angeloni D, Zbar B, Lerman MI, Stanbridge EJ, Minna JD, Protopopov A, Li J, Kashuba V, Klein G, Zabarovsky ER
Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (13) : 7504-7509.
PMID 11390984
 
Frequent epigenetic inactivation of RASSF1A in human bladder carcinoma.
Lee MG, Kim HY, Byun DS, Lee SJ, Lee CH, Kim JI, Chang SG, Chi SG
Cancer research. 2001 ; 61 (18) : 6688-6692.
PMID 11559536
 
The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium.
Lerman MI, Minna JD
Cancer research. 2000 ; 60 (21) : 6116-6133.
PMID 11085536
 
High frequency of promoter hypermethylation of RASSF1A in nasopharyngeal carcinoma.
Lo KW, Kwong J, Hui AB, Chan SY, To KF, Chan AS, Chow LS, Teo PM, Johnson PJ, Huang DP
Cancer research. 2001 ; 61 (10) : 3877-3881.
PMID 11358799
 
Epigenetic inactivation of the RASSF1A 3p21.3 tumor suppressor gene in both clear cell and papillary renal cell carcinoma.
Morrissey C, Martinez A, Zatyka M, Agathanggelou A, Honorio S, Astuti D, Morgan NV, Moch H, Richards FM, Kishida T, Yao M, Schraml P, Latif F, Maher ER
Cancer research. 2001 ; 61 (19) : 7277-7281.
PMID 11585766
 
Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis.
Vos MD, Ellis CA, Bell A, Birrer MJ, Clark GJ
The Journal of biological chemistry. 2000 ; 275 (46) : 35669-35672.
PMID 10998413
 
Hypermethylation of the CpG island of the RASSF1A gene in ovarian and renal cell carcinomas.
Yoon JH, Dammann R, Pfeifer GP
International journal of cancer. Journal international du cancer. 2001 ; 94 (2) : 212-217.
PMID 11668500
 

Citation

This paper should be referenced as such :
Angeloni, D ; Lerman, MI
RASSF1 (Ras association (RalGDS/AF-6) domain family member 1)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(2):93-95.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RASSF1ID377.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 6 ]
  Kidney: Clear cell renal cell carcinoma
Breast: Ductal carcinoma
Liver: Fibrolamellar carcinoma
Lung: Non-small cell carcinoma
Lung: small cell cancer
Kidney: Renal cell carcinomai: an overview


External links

Nomenclature
HGNC (Hugo)RASSF1   9882
Cards
AtlasRASSF1ID377
Entrez_Gene (NCBI)RASSF1  11186  Ras association domain family member 1
Aliases123F2; NORE2A; RASSF1A; RDA32; 
REH3P21
GeneCards (Weizmann)RASSF1
Ensembl hg19 (Hinxton)ENSG00000068028 [Gene_View]  chr3:50367217-50378367 [Contig_View]  RASSF1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000068028 [Gene_View]  chr3:50367217-50378367 [Contig_View]  RASSF1 [Vega]
ICGC DataPortalENSG00000068028
TCGA cBioPortalRASSF1
AceView (NCBI)RASSF1
Genatlas (Paris)RASSF1
WikiGenes11186
SOURCE (Princeton)RASSF1
Genetics Home Reference (NIH)RASSF1
Genomic and cartography
GoldenPath hg19 (UCSC)RASSF1  -     chr3:50367217-50378367 -  3p21.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)RASSF1  -     3p21.3   [Description]    (hg38-Dec_2013)
EnsemblRASSF1 - 3p21.3 [CytoView hg19]  RASSF1 - 3p21.3 [CytoView hg38]
Mapping of homologs : NCBIRASSF1 [Mapview hg19]  RASSF1 [Mapview hg38]
OMIM211980   605082   
Gene and transcription
Genbank (Entrez)AF040703 AF061836 AF102770 AF102771 AF102772
RefSeq transcript (Entrez)NM_001206957 NM_007182 NM_170712 NM_170713 NM_170714 NM_170715 NM_170716 NM_170717
RefSeq genomic (Entrez)NC_000003 NC_018914 NG_023270 NT_022517 NW_004929309
Consensus coding sequences : CCDS (NCBI)RASSF1
Cluster EST : UnigeneHs.476270 [ NCBI ]
CGAP (NCI)Hs.476270
Alternative Splicing GalleryENSG00000068028
Gene ExpressionRASSF1 [ NCBI-GEO ]   RASSF1 [ EBI - ARRAY_EXPRESS ]   RASSF1 [ SEEK ]   RASSF1 [ MEM ]
Gene Expression Viewer (FireBrowse)RASSF1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)11186
GTEX Portal (Tissue expression)RASSF1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NS23   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9NS23  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9NS23
Splice isoforms : SwissVarQ9NS23
PhosPhoSitePlusQ9NS23
Domaine pattern : Prosite (Expaxy)RA (PS50200)    SARAH (PS50951)    ZF_DAG_PE_2 (PS50081)   
Domains : Interpro (EBI)PE/DAG-bd    RA_dom    SARAH_dom    Ubiquitin-rel_dom   
Domain families : Pfam (Sanger)Nore1-SARAH (PF16517)    RA (PF00788)   
Domain families : Pfam (NCBI)pfam16517    pfam00788   
Domain families : Smart (EMBL)C1 (SM00109)  RA (SM00314)  
Conserved Domain (NCBI)RASSF1
DMDM Disease mutations11186
Blocks (Seattle)RASSF1
PDB (SRS)2KZU   
PDB (PDBSum)2KZU   
PDB (IMB)2KZU   
PDB (RSDB)2KZU   
Structural Biology KnowledgeBase2KZU   
SCOP (Structural Classification of Proteins)2KZU   
CATH (Classification of proteins structures)2KZU   
SuperfamilyQ9NS23
Human Protein AtlasENSG00000068028
Peptide AtlasQ9NS23
HPRD05470
IPIIPI00221057   IPI00172514   IPI00172661   IPI00426162   IPI00395780   IPI00426164   IPI00426165   IPI00455193   IPI01021940   
Protein Interaction databases
DIP (DOE-UCLA)Q9NS23
IntAct (EBI)Q9NS23
FunCoupENSG00000068028
BioGRIDRASSF1
STRING (EMBL)RASSF1
ZODIACRASSF1
Ontologies - Pathways
QuickGOQ9NS23
Ontology : AmiGOspindle pole  protein binding  nucleus  cytoplasm  microtubule organizing center  microtubule  plasma membrane  cellular response to DNA damage stimulus  cell cycle arrest  Ras protein signal transduction  zinc ion binding  microtubule cytoskeleton  positive regulation of protein ubiquitination  identical protein binding  protein N-terminus binding  protein stabilization  negative regulation of cell cycle arrest  
Ontology : EGO-EBIspindle pole  protein binding  nucleus  cytoplasm  microtubule organizing center  microtubule  plasma membrane  cellular response to DNA damage stimulus  cell cycle arrest  Ras protein signal transduction  zinc ion binding  microtubule cytoskeleton  positive regulation of protein ubiquitination  identical protein binding  protein N-terminus binding  protein stabilization  negative regulation of cell cycle arrest  
Pathways : KEGGRas signaling pathway    Hippo signaling pathway    Pathways in cancer    MicroRNAs in cancer    Bladder cancer    Non-small cell lung cancer   
NDEx NetworkRASSF1
Atlas of Cancer Signalling NetworkRASSF1
Wikipedia pathwaysRASSF1
Orthology - Evolution
OrthoDB11186
GeneTree (enSembl)ENSG00000068028
Phylogenetic Trees/Animal Genes : TreeFamRASSF1
HOVERGENQ9NS23
HOGENOMQ9NS23
Homologs : HomoloGeneRASSF1
Homology/Alignments : Family Browser (UCSC)RASSF1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRASSF1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RASSF1
dbVarRASSF1
ClinVarRASSF1
1000_GenomesRASSF1 
Exome Variant ServerRASSF1
ExAC (Exome Aggregation Consortium)RASSF1 (select the gene name)
Genetic variants : HAPMAP11186
Genomic Variants (DGV)RASSF1 [DGVbeta]
DECIPHER (Syndromes)3:50367217-50378367  ENSG00000068028
CONAN: Copy Number AnalysisRASSF1 
Mutations
ICGC Data PortalRASSF1 
TCGA Data PortalRASSF1 
Broad Tumor PortalRASSF1
OASIS PortalRASSF1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRASSF1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDRASSF1
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 RASSF1
DgiDB (Drug Gene Interaction Database)RASSF1
DoCM (Curated mutations)RASSF1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RASSF1 (select a term)
intoGenRASSF1
NCG5 (London)RASSF1
Cancer3DRASSF1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM211980    605082   
Orphanet
MedgenRASSF1
Genetic Testing Registry RASSF1
NextProtQ9NS23 [Medical]
TSGene11186
GENETestsRASSF1
Huge Navigator RASSF1 [HugePedia]
snp3D : Map Gene to Disease11186
BioCentury BCIQRASSF1
ClinGenRASSF1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD11186
Chemical/Pharm GKB GenePA34245
Clinical trialRASSF1
Miscellaneous
canSAR (ICR)RASSF1 (select the gene name)
Probes
Litterature
PubMed381 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRASSF1
EVEXRASSF1
GoPubMedRASSF1
iHOPRASSF1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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