ARAP3 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH), Ankyrin repeat domain containing (ANKRD), Sterile alpha motif (SAM) domain containing (SAMD), ArfGAPs
Name	ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3
Description	This gene encodes a phosphoinositide binding protein containing ARF-GAP, RHO-GAP, RAS-associating, and pleckstrin homology domains. The ARF-GAP and RHO-GAP domains cooperate in mediating rearrangements in the cell cytoskeleton and cell shape. It is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6-GAP protein. An alternatively spliced transcript has been found for this gene, but its biological validity has not been determined. [provided by RefSeq, Sep 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARAP3 is a multi‐domain GTPase‐activating protein that acts as a key effector downstream of phosphoinositide 3–kinase (PI3K) and Rap1 signaling. It contains several pleckstrin homology domains that mediate high‐affinity binding to phosphatidylinositol (3,4,5)‐trisphosphate, a feature essential for its recruitment to the plasma membrane and consequent catalytic activation, as well as a sterile alpha motif (SAM) domain that participates in specific protein–protein interactions (1,10). Once activated, ARAP3 accelerates the GTP hydrolysis of small GTPases—most notably RhoA and Arf6—thereby modulating actin cytoskeletal dynamics, cell shape, and adhesion. In epithelial cells, its GAP activity is required for proper regulation of RhoA and Rac1, influencing cell rounding, lamellipodia formation, and the kinetics of cell spreading (1)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In vascular and immune systems, ARAP3 plays a critical modulatory role. It is indispensable for angiogenesis, where loss of ARAP3 function leads to defective endothelial sprouting and lumen formation, culminating in embryonic lethality (5). In neutrophils, ARAP3 functions downstream of Rap1 and PI3K as a negative regulator of β2 integrin activation; by promoting integrin inactivation via a negative feedback loop, ARAP3 prevents inappropriate cell adhesion and hyperresponsiveness, thereby preserving cellular quiescence until proper activation signals are received (3,9). Additionally, ARAP3 has been implicated in the internalization of anthrax toxin by regulating endocytic trafficking, underscoring its broader role in membrane dynamics and vesicle transport (4)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural studies have further elucidated the molecular architecture of ARAP3. Its SAM domain not only contributes to interactions with partners such as the lipid phosphatase Ship2 and the adaptor Odin, but also suggests mechanisms for modulating PI3K signaling (2,6,7). Moreover, crystallographic analysis of its RhoGAP domain has provided insights into its substrate specificity toward RhoA compared with other small GTPases (11). In hematopoietic cells the loss of ARAP3 does not lead to overt cell-autonomous defects, emphasizing a context-dependent function in the regulation of cell adhesion and signaling (8).\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight ARAP3 as a critical regulator of small GTPase activity, integrating upstream phosphoinositide and Rap1 signals to coordinate cytoskeletal remodeling, cell adhesion, migration, and vascular development.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n <!-- Hyperlinked citations -->."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stacey T T I, Zhongzhen Nie, Ashley Stewart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARAP3 is transiently tyrosine phosphorylated in cells attaching to fibronectin and inhibits cell spreading in a RhoGAP-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.01526"}], "href": "https://doi.org/10.1242/jcs.01526"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15546919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15546919"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Judith H Raaijmakers, Laurence Deneubourg, Holger Rehmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PI3K effector Arap3 interacts with the PI(3,4,5)P3 phosphatase SHIP2 in a SAM domain-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2006.12.015"}], "href": "https://doi.org/10.1016/j.cellsig.2006.12.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17314030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17314030"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Laure Gambardella, Karen E Anderson, Claudia Nussbaum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The GTPase-activating protein ARAP3 regulates chemotaxis and adhesion-dependent processes in neutrophils."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-10-312959"}], "href": "https://doi.org/10.1182/blood-2010-10-312959"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21490342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21490342"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Quan Lu, Wensheng Wei, Paul E Kowalski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EST-based genome-wide gene inactivation identifies ARAP3 as a host protein affecting cellular susceptibility to anthrax toxin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0407794101"}], "href": "https://doi.org/10.1073/pnas.0407794101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15569923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15569923"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Laure Gambardella, Myriam Hemberger, Bethany Hughes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PI3K signaling through the dual GTPase-activating protein ARAP3 is essential for developmental angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2001026"}], "href": "https://doi.org/10.1126/scisignal.2001026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20978237"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20978237"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marilisa Leone, Jason Cellitti, Maurizio Pellecchia "}, {"type": "b", "children": [{"type": "t", "text": "The Sam domain of the lipid phosphatase Ship2 adopts a common model to interact with Arap3-Sam and EphA2-Sam."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Struct Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1472-6807-9-59"}], "href": "https://doi.org/10.1186/1472-6807-9-59"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19765305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19765305"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Flavia A Mercurio, Daniela Marasco, Luciano Pirone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heterotypic Sam-Sam association between Odin-Sam1 and Arap3-Sam: binding affinity and structural insights."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chembiochem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbic.201200592"}], "href": "https://doi.org/10.1002/cbic.201200592"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23239578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23239578"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yiwen Song, Jing Jiang, Sonja Vermeren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARAP3 functions in hematopoietic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0116107"}], "href": "https://doi.org/10.1371/journal.pone.0116107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25542002"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25542002"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Barry McCormick, Helen E Craig, Julia Y Chu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Negative Feedback Loop Regulates Integrin Inactivation and Promotes Neutrophil Recruitment to Inflammatory Sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1900443"}], "href": "https://doi.org/10.4049/jimmunol.1900443"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31427445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31427445"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Helen E Craig, John Coadwell, Hervé Guillou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARAP3 binding to phosphatidylinositol-(3,4,5)-trisphosphate depends on N-terminal tandem PH domains and adjacent sequences."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2009.09.025"}], "href": "https://doi.org/10.1016/j.cellsig.2009.09.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19786092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19786092"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hongyu Bao, Fudong Li, Chongyuan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural Basis for the Specific Recognition of RhoA by the Dual GTPase-activating Protein ARAP3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.736140"}], "href": "https://doi.org/10.1074/jbc.M116.736140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27311713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27311713"}]}]}]}
Synonyms	CENTD3, DRAG1
Proteins	ARAP3_HUMAN
NCBI Gene ID	64411
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ARAP3 has 6,011 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 113 datasets.

Click the + buttons to view associations for ARAP3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ARAP3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by ARAP3 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ARAP3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ARAP3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of ARAP3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ARAP3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ARAP3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ARAP3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ARAP3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ARAP3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ARAP3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARAP3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ARAP3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ARAP3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ARAP3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ARAP3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ARAP3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ARAP3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ARAP3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ARAP3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ARAP3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ARAP3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARAP3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ARAP3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with ARAP3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ARAP3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ARAP3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ARAP3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ARAP3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ARAP3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with ARAP3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ARAP3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ARAP3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ARAP3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ARAP3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing ARAP3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ARAP3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ARAP3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ARAP3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing ARAP3 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of ARAP3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.