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FLASH GENE

Symbol

ARHGAP21

contributors: mct/npt - updated : 07-07-2014

HGNC name	Rho GTPase activating protein 21
HGNC id	23725

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Hearing/Equilibrium ear       highly Nervous brain         Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Muscular striatum cardiac   highly Muscular striatum skeletal   highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	liver, brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	one RHO-GAP domain.
	a zinc-dependent phorbol-ester and DAG binding domain
	two small GTPase-binding motifs
	a PDZ, a pleckstrin homology (PH)
	the PH domain and the alpha helical motif, can combine to create a novel mode of binding to Arfs

HOMOLOGY

Homologene

FAMILY

Rho family GTPase

CATEGORY

regulatory , signaling

SUBCELLULAR LOCALIZATION	plasma membrane,junction
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic,vesicle
	intracellular,cytoplasm,cytoskeleton
	intracellular,nucleus
text	recruited from the nuclei and myofilaments to costameres, Z-lines, and intercalated disks of cardiomyocytes after pressure overload
	localizes to the nucleus, cytoplasm, and perinuclear region of the cells depending on the cell type
	ARHGAP21 co-localizes with SUMO2/3 in the cytoplasm and membrane compartments
	transiently localizes to actin structures at cell-cell junctions during cell-cell junction formation, where it interacts with CDC42

basic FUNCTION	involved in intracellular signaling cascade and in cell differentiation
	controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42
	may act as a signaling or scaffold protein of PTK2 and PRKCZ signaling pathways, developing an important function during cardiac stress
	may play a crucial role in the signaling cascade activated by cardiac hypertrophic stimuli
	modulated by mechanical stimuli and can develop an important role during cardiac stress and early hypertrophy
	ARHGAP21 might act as a tumor suppressor gene, but also might be a master regulator of migration having a crucial role in controlling the progression of different tumor types
	acting as a signaling molecule or scaffold protein, orchestrating the CTNNA/PTK2/PRKCZ signaling pathway
	is an important Rho-GAP for CDC42 involved in vesicle trafficking and focal adhesion kinase activity
	participates in cell-cell adhesion formation and cellular migration
	is a Rho-GAP involved in cell-cell junction remodeling and ARHGAP21 affects migration and EMT through TUBA1B interaction and acetylation
	associates with and regulates microtubules, which suggests that this protein may play fundamental roles in development and cancer progression
	concerted action of ARF1, ARHGAP21, and CDC42 to regulate fluid phase endocytosis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	recruited to the Golgi by binding to another small GTPase, ARF1
	interacts with ARF1, ARF6, and CTNNA, important proteins in cytoskeleton and adherent junctions
	interacting with PTK2 (promotes relocation to Z-lines, intercalated disks, and costameres)
	interacts with the C-terminal region of Focal Adhesion Kinase (PTK2)
	dynein and microtubule-dependent Golgi positioning is regulated by ARF1-, coatomer-, and ARHGAP21-dependent CDC42 signaling
	ARHGAP21 presented GAP activity for RHOA and RHOC and induced changes in cell morphology
	negative regulator of Rho-GTPases, particularly CDC42
	interacts and modulates TUBA1B acetylation, and is essential for epithelial-mesenchymal transition (probably affects TUBA1B acetylation through tubulin organization or stabilization, not through this deacetylase)
	action of ARF1, ARHGAP21, and CDC42 to regulate fluid phase endocytosis

cell & other

REGULATION

Other

SUMOylation of ARHGAP21 may represent a way of guiding its functio

ASSOCIATED DISORDERS

ANIMAL & CELL MODELS