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FLASH GENE

Symbol

ARHGEF5

contributors: mct - updated : 21-05-2015

HGNC name	Rho guanine nucleotide exchange factor (GEF) 5
HGNC id	13209

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005435 15 - 5505 NP_005426 - 1597 - 2004 14662653 14662653

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 Digestive intestine large intestine colon     Endocrine pancreas         Reproductive female system breast mammary gland   lowly   female system ovary         male system prostate       Respiratory lung         Urinary kidney

tissue

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

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a pleckstrin homology (PH) domain, required for podosome formation
	a SH3 domain
	GDP-GTP exchange with the DBL homology motif, interacting with N-terminal helices to exclude and prevent activation of Rho GTPases

HOMOLOGY

intraspecies

homolog to GDP-GTP exchange factor MLF2 and NGEF

Homologene

FAMILY

Dbl family of guanine nucleotide exchange factor for Rho GTPases

CATEGORY

regulatory , protooncogene

SUBCELLULAR LOCALIZATION

basic FUNCTION	may be playing an important role in proliferative breast disease
	may be involved in the control of cytoskeletal organization
	acts as an upstream regulator for the RHOA/ROCK-mediated cellular functions
	is important not only for replication fork protection and checkpoint response, but also for replication
	important factor in chemotaxis of a macrophage phage-like
	is crucial for SRC-induced podosome formation
	SRC SH3-binding protein, tyrosine-phosphorylated by SRC and bound to SRC to positively regulate its activity
	acts as a proto-oncogene in human lung adenocarcinoma cell tumorigenesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with MCM2, MCM3, MCM4, MCM5, MCM6, MCM7 (Numata 2010)
	can strongly activate RHOA and RHOB and weakly RHOC and RHOG, but not RAC1, RHOQ, RHOD

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in breast cancer cell lines constitutional       loss of function attenuated allergic airway inflammation tumoral     --over   significantly increased in lung adenocarcinoma tissues and cell lines constitutional     --over   promoted actin stress fiber remodeling through activating RHOA, and the activation of RHOA or CDC42 was required for SRC-induced podosome formation

Susceptibility

Variant & Polymorphism other	five alternative variants predominantly expressed in aggressive primary breast cancer

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS