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FLASH GENE

Symbol

AGAP2

contributors: mct - updated : 08-04-2015

HGNC name	ArfGAP with GTPase domain, ankyrin repeat and PH domain 2
HGNC id	16921

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	18.44 kb     18 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed PIKE-S - splicing 3938 90 836 brain, leukocytes, retina 2004 15118108 nuclear localization NM_014770 18 initiation site 4860 NP_055585 - 835 . brain, spleen, thymus, small intestine, leukocytes . overexpressed in cancer cell lines, amplified in glioblastoma 2004 15118108 PIKE-A binding AKT, mediating cancer cell invasion containing GTPase, PH, ArfGAP, and two ankyrin repeat domains present in PIKE-L but lacks the proline-rich domain containing the N terminus phosphorylated by Cdk5 binds to and enhances the kinase activity of AKT1, thereby promoting cancer progression NM_001122772 19 splicing 5838 NP_001116244 124.5 1192 weakly expressed 2004 15118108 PIKE-L nuclear and cytoplasmic localization important mediator of merlin growth suppression containing an ArfGAP domain and two ankyrin repeats GRM1-HOMER1-PIKE-L complex leading to activation of PI 3-kinase activity and prevention of neuronal apoptosis required for Oligodendrocyte (OL)development and myelination

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 salivary gland       highly Lymphoid/Immune thymus       highly Nervous brain diencephalon amygdala     Visual eye retina

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	ATP/GTP binding site motif A (P loop)
	a pleckstrin homology domain (PH)
	two ankyrin repeats
	a proline-rich extension
	one ARF-GAP domain
	GTPase-like domain having broader trinucleotide specificity

HOMOLOGY

Homologene

FAMILY	RAS superfamily
	centaurin gamma-like family

CATEGORY

signaling

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,nucleus,nucleolus

basic FUNCTION	small GTPase mediating PI3K related Arf signalling
	isoform PIKE-L acting as an important mediator of merlin grotwth suppression
	ARF GTPase-activating protein that regulates endosomal trafficking and is overexpressed in different human cancers
	critical function for AGAP2 in mediating prolactin functions
	ARF1 and AGAP2 have key trafficking functions at the interface between early endosomes and the TGN
	has a critical role in EGF-induced squamous cell carcinoma cell proliferation and may function as a proto-oncogene in squamous cell carcinoma
	GTPase that controls the enzymatic activities of phosphoinositide 3-kinase (PI3K) and AKT1 in the central nervous system (CNS)
	plays a role in the signalling and recycling of beta2-adrenergic receptors
	plays pivotal roles to advance Oligodendrocyte (OL) development and myelinogenesis through AKT1/MTOR activation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

formed a complex with ARRB1 and ARRB2, proteins that are known to regulate beta2-adrenergic receptor signalling and trafficking

INTERACTION

DNA

RNA

small molecule

protein	PTK2 binds the pleckstrin homology domain of AGAP2, and the binding is independent of PTK2 activation following epidermal growth factor receptor stimulation
	activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking
	AGAP1 and AGAP2 can bind to RHOA
	binding NF2 and inhibition of PI3-kinase activity
	functional interaction between FYN, AGAP2, and STAT5A in mediating adipogenesis
	AGAP2 is a novel GNB2L1-interacting protein

cell & other

REGULATION

Other

allosterically regulated through protein binding to the GLD domain

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   amplification     in primary glioblastoma

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Pike-/- mice displayed a severe lactation defect that was characterized by enhanced apoptosis and impaired proliferation of mammary epithelial cells