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FLASH GENE

Symbol

RASGRF2

contributors: mct - updated : 24-06-2019

HGNC name	Ras protein-specific guanine nucleotide-releasing factor 2
HGNC id	9876

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	269.80 kb     27 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006909 27 - 8482 NP_008840 140.6 1237 - 2017 27856453

EXPRESSION

Type

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 Endocrine neuroendocrine pituitary     highly   parathyroid       moderately Nervous brain       moderately Visual eye       predominantly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective       moderately

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two pleckstrin (PH) homology domains
	an ilimaquinone (IQ) domain mediating the calcium-dependent interaction with calmodulin but being dispensable for the Ras-GEF activity
	the DH (DBL-homology) domain mediating interaction with RASGRF1 and EPB49 and being required for RAC1 activation
	a Ras-GEF domain and an N-terminal Ras-GEF domain forming a Ras-binding site and mediate Ras activation
	a Ras exchanger motif (REM),
	a PEST region containing a destruction box (DB),
	a CDC25 domain

mono polymer

homomer , heteromer , oligo

HOMOLOGY

interspecies	homolog to rattus Rasgrf2 (95.9 pc)
	homolog to murine Rasgrf2 (95.5 pc)
	homolog to zebrafish rasgfr2 (86.1 pc)

Homologene

FAMILY

CATEGORY

signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic

basic FUNCTION	functioning as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP
	preferentially activating HRAS in vivo compared to RRAS based on their different types of prenylation
	functioning in synaptic plasticity by contributing to the induction of long term potentiation
	involved in T-cell receptor- and NF-AT-mediated immune responses
	RASGRF1 and -GRF2 may act as adaptors that bind PLCG1 and restrict Ca2+ signalling to the vicinity of focal adhesions, indicating a new role for these GRFs that is required for IL1 induction of the RAS&
	8594;ERK pathway and MMP3 expression
	mediates Ca(2+)-dependent activation of the ERK pathway
	role for RASGRF2 in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse
	RASGRF2 regulates both the basal level and environmentally induced increase of newborn neuron survival, as well as in the induction of a distinct form of synaptic plasticity of newborn neurons that contributes to distinct features of hippocampus-derived learning and memory
	is a calcium sensor and MAPK/ERK activating protein, which has been linked to neurotransmitter release and monoaminergic receptor adaptations
	controls likely dopaminergic signalling and adaptations to alcohol also in other brain regions, beyond the nucleus accumbens
	functional role uncovered for RASGRF2 in control of nuclear migration in cone photoreceptors during postnatal retinal development

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

signal transduction

	regulation of Rho protein signal transduction
	regulation of small GTPase mediated signal transduction

a component

heterooligomer with RASGRF1

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	interacting with Ras and RAC1
	interacting in a calcium-dependent manner with calmodulin
	interacting with CDK5R1 and EPB49
	interacting with the AMPA receptor through GRIA1
	interacting with microtubules
	binding to RAS is necessary for ubiquitination of RASGRF2
	CDC42-GDP can inhibit RRAS2 activation by RASGRF1, RASGRF2
	RASGRF1/2 associates with PLCG1
	ANXA6 acts as a scaffold for RASGRF2 and RAS proteins and its interaction with RASGRF2 is modulated by GTP and/or activation of Ras proteins

cell & other

REGULATION

Other	phosphorylated by CDK5
	ubiquitinated upon interaction with Ras

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral imprinting       frequent methylation and silencing in the carcinogenesis of non-small cell lung cancer (NSCLC)

Susceptibility

to alcoholic cirrhosis

Variant & Polymorphism SNP	A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis compared to alcoholic patients without alcoholic liver disease (ALD)

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

ethanol intake and preference were decreased in Rasgrf2(-/-) mice relative to WT controls