AP2A1 Gene

Name	adaptor-related protein complex 2, alpha 1 subunit
Description	This gene encodes the alpha 1 adaptin subunit of the adaptor protein 2 (AP-2) complex found in clathrin coated vesicles. The AP-2 complex is a heterotetramer consisting of two large adaptins (alpha or beta), a medium adaptin (mu), and a small adaptin (sigma). The complex is part of the protein coat on the cytoplasmic face of coated vesicles which links clathrin to receptors in vesicles. Alternative splicing of this gene results in two transcript variants encoding two different isoforms. A third transcript variant has been described, but its full length nature has not been determined. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The AP2A1 gene encodes the α‐adaptin subunit of the heterotetrameric adaptor protein complex 2 (AP‑2), a pivotal component of the clathrin‐mediated endocytic machinery. As a cargo adaptor, AP2A1 functions to link specific membrane proteins to clathrin, thereby facilitating vesicle formation and receptor internalization. Its role is evident across diverse biological systems and cellular contexts. For instance, studies in human cells have shown that AP2A1 interacts with factors such as m‑Numb, implicating it in the regulation of vesicular trafficking during spermatogenesis and suggesting that its association may influence cell fate decisions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In a related developmental context, AP2A1 has been validated as essential for hematopoietic stem/progenitor cell (HSPC) specification, with its depletion causing defects in HSPC development in zebrafish and impairing human HSC maintenance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the transcript level, AP2A1 expression is fine‐tuned by extensive alternative splicing; seventy‐seven novel splice variants have been identified—many of which harbor premature termination codons and are likely subject to nonsense‐mediated decay—suggesting a potential mechanism for the dynamic regulation of AP2A1 protein levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functionally, AP2A1 is a key mediator of receptor internalization. In epithelial cells, for example, its association with clathrin and other AP‑2 subunits facilitates the endocytosis and subsequent autophagy‐mediated degradation of pore‑forming tight junction proteins such as claudin‑2, thus contributing to the remodeling of cell–cell contacts during nutrient deprivation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in the context of intracellular signaling, increased levels of AP2A1 have been linked to the activation of downstream effectors such as Smad3 in a TGF‑β receptor–dependent but ligand‑independent manner—an effect observed upon overexpression of full‑length IL‑33 (FLIL33)—thereby implicating AP2A1 in modulating profibrotic signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond mammalian cells, the evolutionary conservation of AP2A1 is underscored by studies in Arabidopsis thaliana, where the AP2A1 homolog localizes to the plasma membrane, interacts with clathrin, and is required for the endocytosis of receptors involved in brassinosteroid signaling. This highlights the broad and conserved role of AP2A1 in regulating receptor internalization and signal transduction across plant and animal kingdoms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings illustrate that AP2A1 is integral not only to the formation of clathrin‐coated vesicles but also to the fine‐tuning of receptor signaling and cellular differentiation processes in multiple organisms.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Serena Corallini, Stefania Fera, Laura Grisanti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of the adaptor protein m-Numb in mouse male germ cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reproduction (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/REP-06-0062"}], "href": "https://doi.org/10.1530/REP-06-0062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17127749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17127749"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tianxu Han, Chao-Shun Yang, Kung-Yen Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel genes and networks governing hematopoietic stem cell development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201642395"}], "href": "https://doi.org/10.15252/embr.201642395"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27797851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27797851"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Panagiotis G Adamopoulos, Christos K Kontos, Marios A Diamantopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular cloning of novel transcripts of the adaptor-related protein complex 2 alpha 1 subunit (AP2A1) gene, using Next-Generation Sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2018.08.008"}], "href": "https://doi.org/10.1016/j.gene.2018.08.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30081190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30081190"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ashwinkumar Subramenium Ganapathy, Kushal Saha, Eric Suchanec, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradation through endocytosis and interaction with LC3 and reduces intestinal epithelial tight junction permeability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2021.2016233"}], "href": "https://doi.org/10.1080/15548627.2021.2016233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34964704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34964704"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Irina G Luzina, Rita Fishelevich, Brian S Hampton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Full-length IL-33 regulates Smad3 phosphorylation and gene transcription in a distinctive AP2-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Immunol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellimm.2020.104203"}], "href": "https://doi.org/10.1016/j.cellimm.2020.104203"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32977155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32977155"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Simone Di Rubbo, Niloufer G Irani, Soo Youn Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The clathrin adaptor complex AP-2 mediates endocytosis of brassinosteroid insensitive1 in Arabidopsis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Plant Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1105/tpc.113.114058"}], "href": "https://doi.org/10.1105/tpc.113.114058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23975899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23975899"}]}]}]}
Synonyms	CLAPA1, ADTAA, AP2-ALPHA
Proteins	AP2A1_HUMAN
NCBI Gene ID	160
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AP2A1 has 7,905 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 122 datasets.

Click the + buttons to view associations for AP2A1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AP2A1 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of AP2A1 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 AP2A1 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 AP2A1 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 AP2A1 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 AP2A1 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 AP2A1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving AP2A1 protein from the Biocarta Pathways dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of AP2A1 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 AP2A1 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 AP2A1 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 AP2A1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AP2A1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AP2A1 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 AP2A1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AP2A1 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 AP2A1 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 AP2A1 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 AP2A1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing AP2A1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing AP2A1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing AP2A1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AP2A1 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 AP2A1 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 AP2A1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AP2A1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AP2A1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AP2A1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of AP2A1 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 AP2A1 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 AP2A1 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 AP2A1 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 AP2A1 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 AP2A1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AP2A1 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 AP2A1 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 AP2A1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AP2A1 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 AP2A1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with AP2A1 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 AP2A1 from the GeneSigDB Published Gene Signatures dataset.