ARRB1 Gene

Name	arrestin, beta 1
Description	Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. Arrestin beta 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described. [provided by RefSeq, Jan 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Beta‐arrestin 1 (ARRB1) is emerging as a multifunctional adaptor that not only terminates G protein–coupled receptor (GPCR) signaling but also actively scaffolds and directs a variety of intracellular signaling pathways. ARRB1 acts as an E3‐ligase adaptor that facilitates the recruitment and activation of kinases such as AKT, which in turn promotes MDM2‐mediated degradation of p53, thereby linking chronic stress to DNA damage accumulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, ARRB1 can translocate to the nucleus upon GPCR stimulation and is enriched at specific gene promoters where it recruits histone acetyltransferases (p300) to enhance local histone H4 acetylation and gene transcription, thus directly linking membrane receptor activation to epigenetic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Acting as a molecular scaffold at the plasma membrane, ARRB1 is essential for mediating G protein–independent signaling. It cooperates with activated GPCRs to facilitate RhoA activation and subsequent stress fiber formation—a process that requires concurrent stimulation by Gαq/11—and thereby contributes to cytoskeletal rearrangement and cell motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In some receptor contexts, endogenous ARRB1 can also function as a dominant–negative regulator by attenuating beta–arrestin 2–mediated extracellular signal–regulated kinase (ERK) activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n ARRB1 additionally couples receptors that are not classical GPCRs. For example, following stimulation of the insulin-like growth factor 1 receptor (IGF-1R) and glucagon-like peptide-1 receptor (GLP-1R), ARRB1 couples these receptors to the phosphatidylinositol 3-kinase/Akt pathway, mediating anti-apoptotic signaling through both direct activation of PI3K and subsequent downstream phosphorylation events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, ARRB1 participates in receptor transactivation events leading to cancer cell migration; it assists in assembling complexes (such as those involving c-Src) downstream of receptors like EP4 and LPA receptors, thereby promoting tumor cell motility and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n ARRB1 also modulates receptor homeostasis by serving as an adaptor for ubiquitination. In the context of IGF-1R regulation, ARRB1 is more effective than its homolog ARRB2 at recruiting the oncoprotein MDM2, thereby mediating receptor polyubiquitination and down-regulation, a mechanism with significant implications for cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in signaling and receptor trafficking, ARRB1 is implicated in mediating undesirable side effects of drugs. For example, following nicotinic acid stimulation of GPR109A, ARRB1 engages cytosolic phospholipase A2 to promote arachidonate release, which is critical for the cutaneous flushing response"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and contributes to the regulation of receptor internalization in specific immune cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, differences in subcellular localization between ARRB1 and other arrestin isoforms are governed by intrinsic motifs such as nuclear export signals and specific amino acid residues. These structural determinants not only control ARRB1 trafficking between the nucleus and cytoplasm but also modulate its ability to redistribute binding partners like MDM2 and JNK3, thereby fine-tuning multiple signaling outputs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings portray ARRB1 as a versatile signal transducer that integrates GPCR and non–GPCR signals by orchestrating receptor desensitization, endocytosis, ubiquitination, cytoskeletal reorganization, and even epigenetic modifications. This functional diversity underscores ARRB1’s critical role in cellular homeostasis and disease pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Makoto R Hara, Jeffrey J Kovacs, Erin J Whalen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10368"}], "href": "https://doi.org/10.1038/nature10368"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21857681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21857681"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jiuhong Kang, Yufeng Shi, Bin Xiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2005.09.011"}], "href": "https://doi.org/10.1016/j.cell.2005.09.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16325578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16325578"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "William G Barnes, Eric Reiter, Jonathan D Violin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M412924200"}], "href": "https://doi.org/10.1074/jbc.M412924200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15611106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15611106"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Seungkirl Ahn, Huijun Wei, Tiffany Runyan Garrison, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C300443200"}], "href": "https://doi.org/10.1074/jbc.C300443200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14711824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14711824"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Thomas J Povsic, Trudy A Kohout, Robert J Lefkowitz "}, {"type": "b", "children": [{"type": "t", "text": "Beta-arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M309968200"}], "href": "https://doi.org/10.1074/jbc.M309968200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14534298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14534298"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Julie Quoyer, Christine Longuet, Christophe Broca, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a beta-arrestin 1-mediated ERK1/2 activation in pancreatic beta-cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.067207"}], "href": "https://doi.org/10.1074/jbc.M109.067207"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19915011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19915011"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "F Gregory Buchanan, D Lee Gorden, Pranathi Matta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of beta-arrestin 1 in the metastatic progression of colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0510562103"}], "href": "https://doi.org/10.1073/pnas.0510562103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16432186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16432186"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Timothy T Li, Mistre Alemayehu, Adel I Aziziyeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Beta-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-08-0578"}], "href": "https://doi.org/10.1158/1541-7786.MCR-08-0578"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19609003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19609003"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Leonard Girnita, Sudha K Shenoy, Bita Sehat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "{beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M501129200"}], "href": "https://doi.org/10.1074/jbc.M501129200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15878855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15878855"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Robert W Walters, Arun K Shukla, Jeffrey J Kovacs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI36806"}], "href": "https://doi.org/10.1172/JCI36806"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19349687"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19349687"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Richard A Colvin, Gabriele S V Campanella, Jieti Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intracellular domains of CXCR3 that mediate CXCL9, CXCL10, and CXCL11 function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M403595200"}], "href": "https://doi.org/10.1074/jbc.M403595200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15150261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15150261"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ping Wang, Yalan Wu, Xin Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M208109200"}], "href": "https://doi.org/10.1074/jbc.M208109200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12538596"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12538596"}]}]}]}
Synonyms	ARR1, ARB1
Proteins	ARRB1_HUMAN
NCBI Gene ID	408
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ARRB1 has 11,841 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 136 datasets.

Click the + buttons to view associations for ARRB1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ARRB1 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 ARRB1 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 ARRB1 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 ARRB1 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 ARRB1 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 ARRB1 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 ARRB1 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 ARRB1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving ARRB1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ARRB1 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 ARRB1 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 ARRB1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of ARRB1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARRB1 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 ARRB1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ARRB1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ARRB1 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 ARRB1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ARRB1 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 ARRB1 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 ARRB1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ARRB1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ARRB1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ARRB1 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 ARRB1 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 ARRB1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ARRB1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ARRB1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ARRB1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ARRB1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ARRB1 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 ARRB1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ARRB1 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 ARRB1 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 ARRB1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ARRB1 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 ARRB1 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 ARRB1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ARRB1 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 ARRB1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ARRB1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.