Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol RASSF1 contributors: mct/npt/pgu - updated : 03-09-2018
HGNC name Ras association (RalGDS/AF-6) domain family member 1
HGNC id 9882
Location 3p21.31      Physical location : 50.367.216 - 50.378.367
Synonym name
  • tumor suppressor protein RDA32
  • Ras association domain family 1
  • cardiac-specific ras association domain family 1 protein 2
  • pancreas-specific ras association domain family 1 protein 2
  • tumor suppressor protein RDA32
  • Synonym symbol(s) NORE2A, REH3P21, RDA32, RASSF1A, 123F2, WUGSC:H_LUCA12.5
    DNA
    TYPE functioning gene
    STRUCTURE 11.15 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    text structure
  • two promoters, one upstream exon 1alpha, one between exon 2alpha/beta and 2 gamma
  • abnormal methylation of promoter CpG island in carcinoma
  • MAPPING cloned Y linked N status provisional
    Map pter - VHL VHL - RARB - SEMA3F - TGFBR2 - SEMA3B - BAP1 - HYAL2 - HYAL1 - RASSF1 - MLH1 - FHIT - MAPKAPK3 - cen
    Authors Dammann (00)
    Physical map
    SEMA3F 3p21.31 sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F GNAT1 3p21.2 guanine nucleotide binding protein (G protein), alpha transducing activity polypeptide 1 SLC38A3 3p21.3 solute carrier family 38, member 3 GNAI2 3p21.31 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 SEMA3B 3p21.3 sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3B FLJ38608 3p21.31 hypothetical protein FLJ38608 IFRD2 3p21.3 interferon-related developmental regulator 2 HYAL3 3p21.3 hyaluronoglucosaminidase 3 FUS2 3p21.3 putative tumor suppressor HYAL1 3p21.3 hyaluronoglucosaminidase 1 HYAL2 3p21.3 hyaluronoglucosaminidase 2 PDAP2 3p21.3 PDGFA associated protein 2 RASSF1 3p21.3 Ras association (RalGDS/AF-6) domain family 1 ZMYND10 3p21.3 zinc finger, MYND domain containing 10 NPR2L 101F6 3p21.3 putative tumor suppressor 101F6 PL6 3p21.3 placental protein 6 CACNA2D2 3p21.3 calcium channel, voltage-dependent, alpha 2/delta subunit 2
    regionally located in a 120kb region of common LOH in tumors
    RNA
    TRANSCRIPTS type messenger
    text alternative splicing and promoter usage
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 1676 21.6 189 - 2018 29382819
  • RASSF1B
  • 1 beta/2 alpha/beta
  • 5 splicing 1770 31.1 270 ubiquitous, renal clear cell carcinoma 2018 29382819
  • RASSF1C
  • 2 gamma
  • non tumor suppressive and without effect on CNKSR1-induced apoptosis
  • interacting with ATP2B4b
  • released from the nucleus by DAXX degradation links DNA damage and SAPK/JNK activation
  • 6 - 1968 38.8 340 - 2018 29382819
  • RASSF1A
  • tumor suppressive
  • 1 alpha, 2 alpha/beta
  • missing in all SCLC lines
  • coexpression with CNKSR1 greatly augments CNKSR1-induced apoptosis
  • promoting microtubule stability and suppresses tumorigenesis
  • 6 splicing 1979 39.2 344 - 2018 29382819
    RASSF1D
    5 - 1859 - 189 - 2018 29382819
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   moderately
     liver   moderately
     stomach   moderately
    Endocrineadrenal gland   moderately
     pancreas   highly
    Lymphoid/Immunespleen   highly
    Nervousbrain   highly
     nervecranial nerve  highly
    Reproductivefemale systemuteruscervix moderately
     male systemprostate  highly
    Respiratorylung   moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    cell lineage
    cell lines small cell lung cancer cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminus protein kinase C conserved region 1 domain (C1)
  • cysteine-rich region, similar to the diacylglycerol (DAG)-binding domain (C1 domain) found in the protein kinase C (PKC) family of proteins
  • C terminus homolog to RAS effector NORE1 and MAXP1,
  • RA domain with two PKC phosphorylation sites that evidently play a key role in determining RASSF1A control of microtubule organization
  • both N- and C-terminal regions are required for RASSF1 microtubule localization
  • HOMOLOGY
    interspecies homolog to rattus Rassf1 (90.29 pc)
    Homologene
    FAMILY
    CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • localizes to spindle poles and centromeric areas during metaphase and anaphase, most likely in association with gamma-tubulin, but if it is not on microtubules it can be localized to the nucleus
  • basic FUNCTION
  • involvement in apoptotic signaling, microtubule stabilization and mitotic progression
  • inhibiting the accumulation of CCND1 and thus inducing cell cycle arrest
  • required for prometaphase progression and may be involved in CDC20 regulation during prophase
  • can activate BAX via MOAP1
  • may function as a scaffold to bring together Aurora-A and its activator(s)
  • recruited to MOAP1/TNFRSF1A complexes
  • implicated in prostate tumorigenesis
  • associating with the microtubules, association that alters the microtubule dynamics and seems essential for its tumor suppressive function
  • promotes apoptosis by signaling through the STK3 and LATS1 kinases, leading to stabilization of the YAP1/TP73 transcriptional complex
  • tumor suppressor protein involved in death receptor-dependent apoptosis and it is localized to microtubules
  • role for RASSF1 microtubule localization in eliciting its tumor suppressor function
  • microtubule protein that co-localizes with tubulin and can stabilize microtubules in a paclitaxel (taxol)-like manner
  • activates STK3 and STK4 by preventing their dephosphorylation
  • regulates the cellular ROS levels enhanced by the RAS signaling pathway, and it may function as a tumor suppressor by suppressing DNA damage caused by activated RAS
  • has a tumor suppressive effect as a modulator for ROS production induced by oncogenic K-Ras
  • appear to be able to stimulate YAP1 phosphorylation by the hippo pathway, but the activation of TP73 by RASSF1 can be independent of the canonical hippo pathway
  • is a key regulator in the fine tuning of microtubule dynamics in interphase cells and proper Golgi organization and cell polarity
  • essential role of RASSF1 in regulating TNF signalling in cardiomyocytes
  • RASSF1 modulates apoptosis via the Hippo and BAX pathways but also modulates the cell cycle
  • cell cycle/microtubule effects of RASSF1A are key to its tumor suppressor function rather than its apoptotic effects
  • two novel functions for RASSF1A in the control of DNA repair and protein acetylation
  • as RASSF1A modulates both apoptotic DDR and DNA repair, it may play an important and unanticipated role in coordinating the balance between repair and death after DNA damage
  • function of RASSF1 in stalled replication fork protection
  • tumour suppressor gene epigenetically dysregulated in neuroendocrine tumour (NET)
  • mediates transcription factor selection of YAP1 in stem cells, thereby acting as a functional "switch" between pluripotency and initiation of differentiation 9)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    RASSF1/Salvador pathway is acting independently of RAS
    a component
  • heterodimerizing witn RASSF5
  • pro-apoptotic pathway linking KRas, RASSF1 and BAX that is specifically impaired in some human tumors
  • component of the MST/LATS pathway
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DNA repair protein XPA
  • RASSF5
  • CDC20 and FBXO5 (for inhibition of the anaphase-promoting complex)
  • substrate for PKC (PKC phosphorylation of RASSF1A regulates its ability to reorganize the microtubule network)
  • RASSF1C and spliceosome component PRPF3 interacting with EMC2
  • interacts with STX16 at the midzone and midbody during late mitosis and AURKB is required for this interaction and for the subsequent recruitment of STX16 to the midzone and midbody
  • interacts with the pro-apoptotic mammalian STE20-like kinases STK3 and STK4 and induces their autophosphorylation and activation
  • SAV1 can also bind RASSF1 (RASSF1 requires the presence of Salvador for full apoptotic activity and to activate TP73)
  • interaction of RASSF1 with RAP1A is shown to influence the effect of RASSF1 on microtubule behavior
  • inhibits breast cancer growth, and suppresses estrogen receptor (ESR1) expression and function
  • novel function for TP53 in the methylation of RASSF1 promoter by its interaction with DAXX
  • XPA requires RASSF1 to exert full repair activity, and RASSF1-deficient cells exhibit an impaired ability to repair DNA
  • RASSF1 tumor suppressor regulates BRCA2 at stalled forks
  • MOAP1 is an integral partner to the tumor suppressor protein, (RASSF1), and functions to activate the BCL2 family pro-apoptotic protein BAX
  • RASSF1-dependent microtubule recruitment of PRMT5, suggesting a novel role for RASSF1 in the anchoring of cytosolic PRMT5 to microtubules
  • RASSF1 inhibits the ability of RHEB to suppress autophagy and enhance cell growth, and RHEB may complex with RASSF1 to coordinate Hippo and MTOR signaling
  • RASSF1 limits TGFB1 induced invasion, offering a new framework on how RASSF1 affects YAP1 transcriptional output and elicits its tumor-suppressive function
  • ANKRD1 is a YAP1 target gene that is induced by RASSF1
  • cell & other
    REGULATION
    inhibited by TRF3 (dependent on the activation of intracellular signaling of NF-kappaB involving the C-terminal activating regions (CTARs) of TRF3, and may facilitate its role in transformation of premalignant nasopharyngeal epithelial cells into cancer cells)
    Other phosphorylated by ATM on Ser131 and is involved in the activation of both STK3 and LATS1, leading to the stabilization of TP73
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    by hypermethylation in breast and thyroid carcinoma or HNSCC, pediatric tumors, clear cell and papillary renal cell carcinoma, testicular germ cell tumor, cholangiocarcinoma and prostate carcinoma
    tumoral       loss of function
    by promoter methylation in lung and colorectal cancer, in Wilms tumor and in glioma
    tumoral       loss of function
    by hypermethylation in medulloblastoma, hepatocellular carcinomas, cholangiocarcinomas and cervical carcinoma
    tumoral   deletion    
    in lung, breast, renal cell carcinomas (see DLEC1) and HNSCC
    tumoral       loss of function
    frequent in pancreatic cancer and suggesting an inverse correlation between RASSF1A silencing and K-ras activation in pancreatic cancer
    tumoral       loss of function
    hypermethylation of the promoter associated with a poor prognosis in non small cell lung cancer in patients starting cigarette smoking at an early age
    tumoral     --low  
    by promoter methylation in adenoid cystic carcinoma of the salivary gland, high-grade tumors and tumors with metastasis
    tumoral     --low  
    by DNA hypermethylation may be involved in Gallblader carcinogenesis
    tumoral     --low  
    by promoter hypermethylation in parathyroid tumours
    constitutional     --over  
    inhibits centrosome separation
    Susceptibility to lung adenocarcinoma by tobacco smoker during adolescence
    Variant & Polymorphism SNP , other
  • starting smoking under age 18 was significantly related to RASSF1A methylation in lung adenocarcinoma
  • at codon 133 preferentially associated with lung adenocarcinoma risk
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Rassf1a(-/-) mice are prone to both spontaneous and carcinogen-induced tumorigenesis