AGTRAP Gene

Name	angiotensin II receptor-associated protein
Description	This gene encodes a transmembrane protein localized to the plasma membrane and perinuclear vesicular structures. The gene product interacts with the angiotensin II type I receptor and negatively regulates angiotensin II signaling. Alternative splicing of this gene generates multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Angiotensin II receptor–associated protein (AGTRAP, also known as ATRAP) has emerged as a critical endogenous modulator of angiotensin II type 1 receptor (AT1R) signaling. Initially identified through yeast two‐hybrid screening as a transmembrane protein that interacts with the cytoplasmic domain of AT1R, AGTRAP enhances receptor internalization and thereby selectively attenuates pathological overactivation of AT1R signaling while preserving basal receptor function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the kidney, AGTRAP is widely expressed along the nephron, colocalizing with AT1R in tubular cells, where it modulates sodium reabsorption and blood pressure regulation; genetic deletion or downregulation in renal epithelia is associated with enhanced AT1R surface expression, leading to hypertension and renal dysfunction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": " In the cardiovascular system, overexpression of AGTRAP in cardiomyocytes reduces AT1R density on the cell surface and inhibits downstream hypertrophic signals—such as p38 MAPK phosphorylation and c‐fos promoter activation—thereby counteracting angiotensin II–induced cardiac hypertrophy; similarly, interaction with sarcoplasmic reticulum Ca²⁺‐ATPase (SERCA2a) enhances Ca²⁺ uptake and facilitates rapid ventricular relaxation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " Moreover, AGTRAP modulates intracellular signaling in vascular smooth muscle by interacting with calcium‐modulating cyclophilin ligand (CAML) and by suppressing the calcineurin/NFAT pathway, thereby mitigating vascular senescence and inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Outside the cardiovascular system, in adipose tissue AGTRAP plays a protective role against metabolic dysfunction by reducing inflammation, ameliorating insulin resistance, and curbing adipocyte hypertrophy, as demonstrated in both knockout and transgenic models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": " At the transcriptional level, the human AGTRAP gene is regulated by key transcription factors such as Runx3 and USF1/USF2 through specific promoter elements, while its mRNA stability and cellular localization are influenced by microRNAs and methyl donor availability, linking its expression to both epigenetic modifications and metabolic state."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "18"}]}, {"type": "t", "text": " Additionally, in models of chronic kidney disease and diabetic nephropathy, tubular AGTRAP downregulation correlates with exacerbated tissue remodeling and inflammation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and its altered regulation in podocytes has been linked to glomerular injury via microRNA-mediated suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " In the context of systemic inflammation and noncommunicable diseases, leukocyte expression of AGTRAP correlates with inflammatory markers, further underscoring a role in immune regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": " Finally, emerging evidence even implicates AGTRAP in the broader regulation of Ca²⁺ handling essential for fast, precise, and sustained neurotransmission"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": ", emphasizing its pleiotropic influence across multiple organ systems. Collectively, these findings highlight AGTRAP as a multifaceted regulator that tempers AT1R activation and its deleterious downstream effects, thereby offering a promising therapeutic target in cardiovascular, renal, metabolic, and potentially neurodegenerative disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "28"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marco Lopez-Ilasaca, Xiushi Liu, Koichi Tamura, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Ablation of Immunoproteasome β5i Subunit Suppresses Hypertensive Retinopathy by Blocking ATRAP Degradation in Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymthe.2019.09.025"}], "href": "https://doi.org/10.1016/j.ymthe.2019.09.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31636038"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31636038"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Sudhir Jain, Anita Rana, Kavita Jain, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Age-Related Expression of Human AT1R Variants and Associated Renal Dysfunction in Transgenic Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hypertens (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ajh/hpy121"}], "href": "https://doi.org/10.1093/ajh/hpy121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30084918"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30084918"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Dandan Wang, Xiaoying Jin, Mengxia Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.69134"}], "href": "https://doi.org/10.7150/ijbs.69134"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35414770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35414770"}]}]}]}
Synonyms	ATRAP
Proteins	ATRAP_HUMAN
NCBI Gene ID	57085
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AGTRAP has 5,446 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 105 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

AGTRAP 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 AGTRAP 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 AGTRAP 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 AGTRAP 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 AGTRAP 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 AGTRAP 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 AGTRAP 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 AGTRAP gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of AGTRAP 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 AGTRAP 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 AGTRAP gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AGTRAP protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AGTRAP 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 AGTRAP gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AGTRAP 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 AGTRAP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing AGTRAP protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AGTRAP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing AGTRAP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AGTRAP 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 AGTRAP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AGTRAP gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AGTRAP gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AGTRAP gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of AGTRAP 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 AGTRAP 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 AGTRAP 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 AGTRAP 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 AGTRAP 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 AGTRAP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AGTRAP 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 AGTRAP 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 AGTRAP gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AGTRAP 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 AGTRAP from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with AGTRAP gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with AGTRAP gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with AGTRAP 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 AGTRAP from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of AGTRAP gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of AGTRAP gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.