AP2A2 adaptor related protein complex 2 subunit alpha 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AP2A2provided by HGNC
Official Full Name: adaptor related protein complex 2 subunit alpha 2provided by HGNC
Primary source: HGNC:HGNC:562
See related: Ensembl:ENSG00000183020 MIM:607242; AllianceGenome:HGNC:562
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: HIP9; HYPJ; ADTAB; HIP-9; CLAPA2
Summary: The protein encoded by this gene is a subunit of the AP-2 adaptor protein complex, which is involved in linking lipid and protein membrane components with the clathrin lattice. This interaction supports the formation of clathrin-coated vesicles, and the encoded subunit aids in the process by binding polyphosphoinositide-containing lipids in the cell membrane. [provided by RefSeq, Nov 2016]
Expression: Ubiquitous expression in spleen (RPKM 30.8), brain (RPKM 22.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.5

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (925870..1012240)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (977298..1071157)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (925870..1012240)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

We found evidence of late-onset Alzheimer disease-associated genetic polymorphism within an exon of Mucin 6 (MUC6) and immediately downstream from another gene: AP2A2
Title: Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene.
T allele and TT genotype in rs7396366, closest to the AP2A2 gene, are linked to an increased risk of coronary artery disease and its severity in a Chinese population.
Title: A genetic variant near adaptor-related protein complex 2 alpha 2 subunit gene is associated with coronary artery disease in a Chinese population.
AP2 has evolved as a key regulatory node to coordinate clarhtin-coated pit formation and cargo sorting and ensure high spatial and temporal regulation of cathrin-mediated endocytosis.
Title: Regulation of clathrin-mediated endocytosis by hierarchical allosteric activation of AP2.
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.
Clathrin-dependent endocytosis of human CD317 from the cell surface lipid rafts is mediated by direct interaction with alpha-adaptin.
Title: HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin.
The mutation of lysine-297 and arginine-340 on the alpha-adaptin specifically inhibits the ability of Nef to bind AP-2 and downregulate CD4.
Title: A basic patch on alpha-adaptin is required for binding of human immunodeficiency virus type 1 Nef and cooperative assembly of a CD4-Nef-AP-2 complex.
the AP-2 complex is not associated with the endocytosed plasma membrane-associated clathrin
Title: The AP-2 complex is excluded from the dynamic population of plasma membrane-associated clathrin.

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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

EBI GWAS Catalog

Description
Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

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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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	HIV-1 Env gp41 requires the conserved membrane-proximal AP2A2 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	Genome-wide shRNA screening identifies AP2A2, which is required for HIV-1 Nef-induced downregulation of CD4 in HeLa CD4+ cells	PubMed
	nef	Knocking down AP-2 enhances Nef activity by causing increased delivery of HLA-A2 to a prelysosomal compartment	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	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

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

D11S2921 (e-PCR)
- UniSTS:152074

SHGC-81865 (e-PCR)
- UniSTS:103984

PMC156606P3 (e-PCR)
- UniSTS:271410

D8S2278 (e-PCR)
- UniSTS:473906

PMC156606P4 (e-PCR)
- UniSTS:271411

D8S2279 (e-PCR)
- UniSTS:473907

L18426 (e-PCR)
- UniSTS:34648

STS-W67158 (e-PCR)
- UniSTS:80989

D16S325 (e-PCR)
- UniSTS:147089

G09846 (e-PCR)
- UniSTS:54174

RH48949 (e-PCR)
- UniSTS:2792

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 disordered domain specific binding	IEA Inferred from Electronic Annotation more info
enables lipid binding	IEA Inferred from Electronic Annotation more info
enables molecular_function	ND No biological Data available more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
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 intracellular protein transport	IEA Inferred from Electronic Annotation more info
involved_in postsynaptic neurotransmitter receptor internalization	NAS Non-traceable Author Statement more info	PubMed
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 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 cytoplasmic vesicle	ISS Inferred from Sequence or Structural Similarity more info
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 ficolin-1-rich granule membrane	TAS Traceable Author Statement more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynapse	IEA Inferred from Electronic Annotation more info
located_in secretory granule membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: AP-2 complex subunit alpha-2

Names: 100 kDa coated vesicle protein C; adapter-related protein complex 2 subunit alpha-2; adaptin, alpha B; adaptor related protein complex 2 alpha 2 subunit; alpha-adaptin C; Huntingtin interacting protein J; alpha2-adaptin; clathrin assembly protein complex 2 alpha-C large chain; clathrin-associated/assembly/adaptor protein, large, alpha 2; huntingtin yeast partner J; huntingtin-interacting protein 9; plasma membrane adaptor HA2/AP2 adaptin alpha C 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_001242837.2 → NP_001229766.1 AP-2 complex subunit alpha-2 isoform 1

See identical proteins and their annotated locations for NP_001229766.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AK223558, AP006477, BU735076, DB461570

Consensus CDS

CCDS73234.1

UniProtKB/TrEMBL

B7Z5S9

Related

ENSP00000327694.5, ENST00000332231.9

Conserved Domains (5) summary

smart00809
Location:718 → 821

Alpha_adaptinC2; Adaptin C-terminal domain

pfam01602
Location:29 → 591

Adaptin_N; Adaptin N terminal region

pfam02296
Location:827 → 935

Alpha_adaptin_C; Alpha adaptin AP2, C-terminal domain

pfam12717
Location:163 → 235

Cnd1; non-SMC mitotic condensation complex subunit 1

sd00044
Location:332 → 355

HEAT; HEAT repeat [structural motif]
NM_012305.4 → NP_036437.1 AP-2 complex subunit alpha-2 isoform 2

See identical proteins and their annotated locations for NP_036437.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the central coding region, compared to variant 1, resulting in an isoform (2) that is 1 aa shorter than isoform 1.

Source sequence(s)

AP006477, BC006155, BU735076, DB461570

Consensus CDS

CCDS44512.1

UniProtKB/Swiss-Prot

O75403, O94973, Q53ET1, Q96SI8

UniProtKB/TrEMBL

B7Z5S9

Related

ENSP00000413234.3, ENST00000448903.7

Conserved Domains (5) summary

smart00809
Location:717 → 820

Alpha_adaptinC2; Adaptin C-terminal domain

pfam01602
Location:29 → 590

Adaptin_N; Adaptin N terminal region

pfam02296
Location:826 → 934

Alpha_adaptin_C; Alpha adaptin AP2, C-terminal domain

pfam12717
Location:163 → 235

Cnd1; non-SMC mitotic condensation complex subunit 1

sd00044
Location:331 → 354

HEAT; HEAT repeat [structural motif]

RNA

NR_144509.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice junction and lacks an alternate exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AP006477, AP006623

Related

ENST00000687890.1
NR_144510.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AP006477, AP006623

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

925870..1012240

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047426480.1 → XP_047282436.1 AP-2 complex subunit alpha-2 isoform X1
XM_047426479.1 → XP_047282435.1 AP-2 complex subunit alpha-2 isoform X1
XM_011519930.4 → XP_011518232.1 AP-2 complex subunit alpha-2 isoform X3

UniProtKB/TrEMBL

A0A8I5KPP9

Related

ENSP00000431630.1, ENST00000528815.5

Conserved Domains (3) summary

pfam01602
Location:29 → 591

Adaptin_N; Adaptin N terminal region

pfam12717
Location:163 → 235

Cnd1; non-SMC mitotic condensation complex subunit 1

sd00044
Location:369 → 398

HEAT; HEAT repeat [structural motif]
XM_011519929.2 → XP_011518231.1 AP-2 complex subunit alpha-2 isoform X1

See identical proteins and their annotated locations for XP_011518231.1

UniProtKB/TrEMBL

A0A0G2JS82

Conserved Domains (3) summary

smart00809
Location:642 → 745

Alpha_adaptinC2; Adaptin C-terminal domain

COG5096
Location:1 → 525

COG5096; Vesicle coat complex, various subunits [Intracellular trafficking, secretion, and vesicular transport]

pfam02296
Location:751 → 859

Alpha_adaptin_C; Alpha adaptin AP2, C-terminal domain
XM_047426482.1 → XP_047282438.1 AP-2 complex subunit alpha-2 isoform X1
XM_047426485.1 → XP_047282441.1 AP-2 complex subunit alpha-2 isoform X1
XM_047426484.1 → XP_047282440.1 AP-2 complex subunit alpha-2 isoform X2
XM_047426481.1 → XP_047282437.1 AP-2 complex subunit alpha-2 isoform X1