AP2A1 adaptor related protein complex 2 subunit alpha 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AP2A1provided by HGNC
Official Full Name: adaptor related protein complex 2 subunit alpha 1provided by HGNC
Primary source: HGNC:HGNC:561
See related: Ensembl:ENSG00000196961 MIM:601026; AllianceGenome:HGNC:561
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ADTAA; CLAPA1; AP2-ALPHA
Summary: 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]
Expression: Broad expression in testis (RPKM 42.9), brain (RPKM 24.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.33

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (49767001..49807114)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (52767146..52807252)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (50270258..50310371)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Results revealed thirteen novel splice junctions of previously annotated exons. Consecutive nested PCRs led to the determination of the primary structure of seventy-seven novel AP2A1 transcripts, all of which were shown to comprise at least one premature translation termination codon, thus representing nonsense-mediated mRNA decay candidates.
Title: Molecular cloning of novel transcripts of the adaptor-related protein complex 2 alpha 1 subunit (AP2A1) gene, using Next-Generation Sequencing.
AP-2alpha depletion enhanced apoptosis, demonstrating that disrupting the HIV-1 Nef:AP-2alpha interaction limits Nef-mediated apoptosis.
Title: The interaction between HIV-1 Nef and adaptor protein-2 reduces Nef-mediated CD4(+) T cell apoptosis.
These results lead to a model for the docking of the full AP-2 tetramer to membranes as bound to Nef, such that the cytosolic tail of CD4 is situated to interact with its binding site on Nef.
Title: How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4.
A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration.
Title: Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration.
nef usurps AP-2 complexes to dysregulate Ii (invariant chain (Ii)/major histocompatibility complex class II) trafficking and potentially interfere with antigen presentation in the context of MHC-II
Title: Competition model for upregulation of the major histocompatibility complex class II-associated invariant chain by human immunodeficiency virus type 1 Nef.
AP2alpha negatively regulates HIV-1 replication in the process of nuclear translocation of viral DNA in the cytoplasm or the perinuclear region.
Title: Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of adaptor-related protein complex 2, alpha 1 subunit (AP2A1) by siRNAs significantly enhances HIV-1 replication in human acute monocytic leukemia cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	HIV-1 Env gp41 requires the conserved membrane-proximal AP2A1 binding site in the gp41 cytoplasmic tail to evade antibody-dependent cell-mediated cytotoxicity (ADCC) via membrane-proximal endocytosis	PubMed
	env	Two independent motifs, a membrane proximal conserved GYxxO motif (residues 711-715) and a C-terminal dileucine motif (residues 855-856), of the HIV-1 gp41 protein mediate endocytosis through interaction with the clathrin adaptor AP-2	PubMed
	env	The cytoplasmic domain (residues 707-856) of HIV-1 gp41 interacts with whole clathrin-associated AP-1 and AP-2 adaptor complexes	PubMed
Nef	nef	Mutation of Arg to Glu at position 134 in HIV-1 Nef abolishes its binding to the AP-2 alpha1-sigma2 hemicomplex	PubMed
	nef	HIV-1 Nef (residues 54-203) binds with low micromolar affinity to the AP-2 alpha (residues 1-392)-sigma2 (residues 1-142) hemicomplex. The central loop (residues 149-179) and the core (residues 55-65) of Nef are involved in the binding	PubMed
	nef	A diacidic motif DD174/175 in HIV-1 Nef is required for direct binding to AP-2 alpha and the binding is dependent on electrostatic interactions, thus leading to Nef-mediated CD4 downregulation	PubMed
	nef	Interaction of HIV-1 Nef with AP-2 alpha-sigma dimer is required for Nef-mediated CD4 downregulation. The dileucine L164L165 and M168L170 motifs bind to the sigma unit, while the acidic motif E174 and D175 binds to the alpha unit	PubMed
	nef	Knocking down AP-2 enhances Nef activity by causing increased delivery of HLA-A2 to a prelysosomal compartment	PubMed
	nef	K295, K297, K298, and R340 basic residues on the AP-2 alpha subunit are required for its binding to HIV-1 Nef. The K297 and R340 residues are required for Nef-induced CD4 downregulation and the cooperative assembly of a Nef-CD4-AP-2 complex	PubMed
Pr55(Gag)	gag	HIV-1 Gag binds to AP-2, and this binding is dependent on tyrosine residue 132 and valine residue 135 at the matrix-capsid junction in the Gag polyprotein	PubMed
Tat	tat	HIV-1 Tat enters T cells by using clathrin/AP2-mediated endocytosis followed by low-pH-induced and Hsp90-assisted endosomal translocation, which leads to cell responses that are induced from the cytosol	PubMed
Vpu	vpu	Vpu interacts with clathrin adaptors AP1G1 and AP2A1 in tetherin-expressing cells and this interaction is regulated by serine phosphorylation of Vpu and Vpu binding to tetherin	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Ap2a1 (e-PCR), detects polymorphism
- UniSTS:141096

MARC_13831-13832:1006881711:1 (e-PCR)
- UniSTS:267573

RH102233 (e-PCR)
- UniSTS:96567

STS-AA031950 (e-PCR)
- UniSTS:31074

MARC_23449-23450:1027106382:1 (e-PCR)
- UniSTS:268701

RH75669 (e-PCR)
- UniSTS:91069

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables clathrin adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to clathrin adaptor activity	TAS Traceable Author Statement more info	PubMed
enables low-density lipoprotein particle receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Golgi to endosome transport	NAS Non-traceable Author Statement more info	PubMed
involved_in clathrin-dependent endocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in clathrin-dependent endocytosis	IDA Inferred from Direct Assay more info	PubMed
involved_in clathrin-dependent endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in clathrin-dependent endocytosis	NAS Non-traceable Author Statement more info	PubMed
involved_in clathrin-dependent endocytosis	TAS Traceable Author Statement more info	PubMed
involved_in endocytosis	NAS Non-traceable Author Statement more info	PubMed
involved_in intracellular protein transport	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of hyaluronan biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of hyaluronan biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron projection development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of receptor-mediated endocytosis	IEA Inferred from Electronic Annotation more info
involved_in postsynaptic neurotransmitter receptor internalization	NAS Non-traceable Author Statement more info	PubMed
involved_in synaptic vesicle endocytosis	IEA Inferred from Electronic Annotation more info
involved_in vesicle-mediated transport	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of AP-2 adaptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of AP-2 adaptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of AP-2 adaptor complex	NAS Non-traceable Author Statement more info	PubMed
part_of AP-2 adaptor complex	TAS Traceable Author Statement more info	PubMed
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
part_of clathrin coat of trans-Golgi network vesicle	NAS Non-traceable Author Statement more info	PubMed
located_in clathrin-coated endocytic vesicle	NAS Non-traceable Author Statement more info	PubMed
located_in clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in cytoplasmic side of plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in endolysosome membrane	TAS Traceable Author Statement more info
located_in filopodium tip	IEA Inferred from Electronic Annotation more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic endocytic zone	IEA Inferred from Electronic Annotation more info
located_in synaptic vesicle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: AP-2 complex subunit alpha-1

Names: 100 kDa coated vesicle protein A; adapter-related protein complex 2 alpha-1 subunit; adapter-related protein complex 2 subunit alpha-1; adaptin, alpha A; adaptor protein complex AP-2 subunit alpha-1; adaptor related protein complex 2 alpha 1 subunit; alpha-adaptin A; alpha1-adaptin; clathrin assembly protein complex 2 alpha-A large chain; clathrin-associated/assembly/adaptor protein, large, alpha 1; plasma membrane adaptor HA2/AP2 adaptin alpha A subunit

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_014203.3 → NP_055018.2 AP-2 complex subunit alpha-1 isoform 1

See identical proteins and their annotated locations for NP_055018.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform of this protein.

Source sequence(s)

AC006942, AC011495

Consensus CDS

CCDS46148.1

UniProtKB/Swiss-Prot

O95782, Q96CI7, Q96PP6, Q96PP7, Q9H070

Related

ENSP00000351926.4, ENST00000359032.10

Conserved Domains (4) summary

sd00044
Location:332 → 355

HEAT; HEAT repeat [structural motif]

pfam01602
Location:29 → 591

Adaptin_N; Adaptin N terminal region

pfam02296
Location:864 → 972

Alpha_adaptin_C; Alpha adaptin AP2, C-terminal domain

pfam02883
Location:751 → 858

Alpha_adaptinC2; Adaptin C-terminal domain
NM_130787.3 → NP_570603.2 AP-2 complex subunit alpha-1 isoform 2

See identical proteins and their annotated locations for NP_570603.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks a 66 nt internal exon but maintains the reading frame, as compared to variant 1. Isoform 2 lacks 22 internal aa as compared to isoform 1.

Source sequence(s)

AC006942, AC011495

Consensus CDS

CCDS46149.1

UniProtKB/Swiss-Prot

O95782

Related

ENSP00000346246.4, ENST00000354293.10

Conserved Domains (4) summary

sd00044
Location:332 → 355

HEAT; HEAT repeat [structural motif]

pfam01602
Location:29 → 591

Adaptin_N; Adaptin N terminal region

pfam02296
Location:842 → 950

Alpha_adaptin_C; Alpha adaptin AP2, C-terminal domain

pfam02883
Location:729 → 836

Alpha_adaptinC2; Adaptin C-terminal domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

49767001..49807114

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011526556.3 → XP_011524858.1 AP-2 complex subunit alpha-1 isoform X1

Conserved Domains (4) summary

smart00809
Location:772 → 875

Alpha_adaptinC2; Adaptin C-terminal domain

pfam01602
Location:46 → 608

Adaptin_N; Adaptin N terminal region

pfam02296
Location:881 → 989

Alpha_adaptin_C; Alpha adaptin AP2, C-terminal domain

sd00044
Location:349 → 372

HEAT; HEAT repeat [structural motif]
XM_011526557.4 → XP_011524859.1 AP-2 complex subunit alpha-1 isoform X2

Conserved Domains (4) summary

smart00809
Location:750 → 853

Alpha_adaptinC2; Adaptin C-terminal domain

pfam01602
Location:46 → 608

Adaptin_N; Adaptin N terminal region

pfam02296
Location:859 → 967

Alpha_adaptin_C; Alpha adaptin AP2, C-terminal domain

sd00044
Location:349 → 372

HEAT; HEAT repeat [structural motif]