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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	alternative splicing and promoter usage

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_170712 6 splicing 1676 21.6 189 - 2018 29382819 RASSF1B 1 beta/2 alpha/beta NM_170713 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 NM_007182 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 NM_170714 6 splicing 1979 39.2 344 - 2018 29382819 RASSF1D NM_001206957 5 - 1859 NP_001193886 - 189 - 2018 29382819

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       moderately   liver       moderately   stomach       moderately Endocrine adrenal gland       moderately   pancreas       highly Lymphoid/Immune spleen       highly Nervous brain       highly   nerve cranial nerve     highly Reproductive female system uterus cervix   moderately   male system prostate     highly Respiratory lung       moderately Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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 tumoral     --low   more pronounced in cervical tumors with lymph node metastases compared with non-metastatic ones

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