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FLASH GENE

Symbol

ARHGEF2

contributors: shn - updated : 06-09-2017

HGNC name	Rho/Rac guanine nucleotide exchange factor (GEF) 2
HGNC id	682

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	31.34 kb     22 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D1S303 - D1S1595 - ARHGEF2 - D1S2721 - D1S2624 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004723 (transcript variant 3) 22 splicing 4119 NP_004714 - 958 - - NM_001162384 (transcript variant 2) 22 splicing 4191 NP_001155856 - 985 - - NM_001162383 (transcript variant 1) 22 - 4194 NP_001155855 - 986 - -

EXPRESSION

Type

widely

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 Cardiovascular heart       highly Digestive liver       highly Endocrine pancreas       highly Lymphoid/Immune spleen       highly Nervous brain       highly Reproductive female system ovary     highly   male system testis     highly Respiratory lung       highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	associates with microtubules via its N-terminal C1 domain, which is known to regulate its activity
	a Dbl homology domain in tandem with a pleckstin homology (PH) domain
	a C terminal domain for suppression of guanine nucleotide exchange activity by microtubules
	the C terminal domain contains a coiled-coil domain proline-rich motif that may interact with Src homology 3 domain-containing proteins and a potential binding site for 14-3-3 proteins

conjugated

HOMOLOGY

interspecies	ortholog to Arhgef2, Mus musculus
	ortholog to Arhgef2, Rattus norvegicus

Homologene

FAMILY

Dbl family GEFs specific for Rho

CATEGORY

regulatory , signaling

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle
	intracellular,cytoplasm,cytoskeleton,microtubule
text	colocalizing with microtubules
	colocalized with ASAP1 in podosomes

basic FUNCTION	involved in regulation of signal transduction cascades from extracellular stimuli to cell nucleus and cytoskeleton
	stimulating guanine nucleotide exchange for Rac and Rho
	modulates localized RhoA activation during cytokinesis under the control of mitotic kinases
	guanine exchange factor-H1 for RhoA, that is transcriptionally activated by the induction of mutant TP53 proteins, thereby accelerating tumor cell proliferation
	mediates cross-talk between microtubules and the actin cytoskeleton
	regulate spindle orientation in non-neural cells
	required to determine the orientation of mitotic precursor cell divisions in vivo and its interaction with Tctex-1 is necessary to regulate cortical neurogenesis
	important in embryonic neural precursors, a part of an essential pathway that regulates the genesis of neurons from cortical precursor cells, potentially by regulating mitotic spindle orientation
	essential for the normal genesis of neurons from embryonic radial precursors
	negative regulator of podosomes
	potentially responsible for the increased RhoA activity necessary for podosome belt disassembly
	may affect the regulation of the microtubule organization
	may promotes tubulin-acetylation following microtubule binding and stabilization
	with ARHGEF10, ARHGEF2, ARHGEF12, PLEKHG1 and ARHGEF28, are involved in cyclic-stretch-induced perpendicular reorientation of endothelial cells

CELLULAR PROCESS	cell cycle, division, mitosis

PHYSIOLOGICAL PROCESS

neurogenesis

text	essential for neurogenesis

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	tight junction-associated adaptor cingulin (CGN)
	semaphorin 4D (Sema4D)
	dynein, light chain, Tctex-type 1 (DYNLT1)
	ARHGEF2 and EXOC1 interact in trans-Golgi network and centrosomes, as well as in exocyst structures or complexes that move along microtubules to the plasma membrane, consistent with a functional association in both early and late stages of vesicular trafficking
	ARHGEF2, a guanine nucleotide exchange factor for RHOA, directly interacts with cingulin, a junctional adaptor
	binding partner of the BAR domain of ASAP1
	MARK2 is a substrate for ARHGEF2
	CAMSAP3-anchored non-centrosomal microtubules capture ARHGEF2 more efficiently than other microtubules do and a balance between these microtubules is important to maintain proper actin organization
	role for association of ARHGEF2 with CGN as the mechanism of RHOA pathway inactivation

cell & other

REGULATION

Phosphorylated by

MARK2, that phosphorylates ARHGEF2 at three serine residues located close to the C1 domain and regulates the microtubule binding ability of ARHGEF2

Other	phosphorylated and regulated by p21-activated kinase 1
	regulated by an interaction with microtubules
	negatively regulated by Tctex-1 (Dynlt1)
	activated when it is released from microtubules

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   contributes to the tumor progression phenotype associated with the TP53 mutation

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

genetic knockdown of mouse Arhgef2 in cortical precursors either in culture or in vivo inhibits neurogenesis and maintained cells as cycling radial precursors