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FLASH GENE

Symbol

ARHGEF6

contributors: mct - updated : 10-01-2017

HGNC name	Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6
HGNC id	685

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MRX46 mental retardation, 46
Location	Xq26.3      Physical location : 135.747.713 - 135.863.503
Synonym name	PAK-interacting exchange factor alpha
	rho guanine nucleotide exchange factor 6
	Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6
	Rac/Cdc42 guanine exchange factor (GEF) 6
Synonym symbol(s)	COOL2, COOL-2, ALPHAPIX, KIAA0006, ALPHA-PIX, PIXA

DNA

TYPE	functioning gene
STRUCTURE	116.11 kb     22 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_004840 22 - 5282 NP_004831 - 776 - 2015 26507661 NM_001306177 21 - 4820 NP_001293106 - 622 - 2015 26507661

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 blood / hematopoietic spleen       highly   thymus       highly Cardiovascular heart       highly Nervous brain         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid         Muscular         Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal calponin homology domain,(unique to ARHGEF6)
	a SH3 homology domain
	a Dbl and a pleckstrin homology (PH) domains

HOMOLOGY

interspecies

homolog to rattus arhgef6

Homologene

FAMILY

cytoplasmic proteins family

CATEGORY

regulatory , signaling

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,intermed filament
text	lamellipodia
	is localized to dendritic spines

basic FUNCTION	activator of Ras-like family of Rho proteins by exchanging bound GDP for GTP
	putatively involved in axonal outgrowth,control of shape and size of dendrites
	invoved in integrin-mediated signaling leading to activation of the GTPases RAC1 and/or CDC42
	ARHGEF6 is localized in dendritic spines where it contributes to regulate spine morphogenesis probably by acting through a downstream activation of PAK3
	ARHGEF6 and GIT2 are required for neuronal differentiation
	RELN and the CDC42/RAC1 guanine nucleotide exchange factor ARHGEF6 promote dendritic Golgi translocation in hippocampal neurons
	is a regulator of thymocyte migration and subsequent arrest that is linked to positive selection
	recycling regulator ARHGEF6 and the degradation factor CBL closely cooperate in the regulation of EGFR trafficking
	ARHGEF6 and ARHGEF7, respectively, are guanine nucleotide exchange factors (activators) for the Rho family small GTP-binding protein family members RAC1 and CDC42

CELLULAR PROCESS	cell life, proliferation/growth
	cell migration & motility

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with PARVB (involved in reorganization of subsarcolemmal cytoskeletal actin by activation of RAC1 through ARHGEF6 and ARHGEF7 in skeletal muscle) (Matsuda 2008)
	CBL negatively regulates ARHGEF6-mediated cell migration and invasion and the lack of CBL in the C6 and A172 glioma cells is respon
	phosphorylated state of ARHGEF6 was required to activate first RAC1 and subsequently PYGM
	interacts with the E3 ubiquitin ligase CBL, an enzyme that attaches ubiquitin to EGFR, thereby labelling this tyrosine kinase receptor for lysosomal degradation
	function of ARHGEF6 as a strong promoter of EGFR recycling
	ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex

cell & other

REGULATION

Phosphorylated by

PRKCQ (to activate RAC1 and consequently PYGM, PRKCQ phosphorylates ARHGEF6 in T cells)

ASSOCIATED DISORDERS

corresponding disease(s)

MRX46

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     deleted in gastric carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

imbalance in activity of different Rho GTPases may underlie altered neuronal connectivity and impaired synaptic function and cognition in Arhgef6 knockout mice