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 ... See more...

Aliases for AP2A1 Gene

Aliases for AP2A1 Gene

  • Adaptor Related Protein Complex 2 Subunit Alpha 1 2 3 5
  • Clathrin Assembly Protein Complex 2 Alpha-A Large Chain 3 4
  • Plasma Membrane Adaptor HA2/AP2 Adaptin Alpha A Subunit 3 4
  • Adaptor Related Protein Complex 2 Alpha 1 Subunit 2 3
  • Adaptor Protein Complex AP-2 Subunit Alpha-1 3 4
  • 100 KDa Coated Vesicle Protein A 3 4
  • AP-2 Complex Subunit Alpha-1 3 4
  • Alpha-Adaptin A 3 4
  • Alpha1-Adaptin 3 4
  • CLAPA1 3 4
  • ADTAA 3 4
  • Clathrin-Associated/Assembly/Adaptor Protein, Large, Alpha 1 3
  • Adapter-Related Protein Complex 2 Alpha-1 Subunit 3
  • Adapter-Related Protein Complex 2 Subunit Alpha-1 3
  • Adaptor-Related Protein Complex 2 Subunit Alpha-1 4
  • Adaptin, Alpha A 3
  • AP2-ALPHA 3

External Ids for AP2A1 Gene

Previous HGNC Symbols for AP2A1 Gene

  • CLAPA1
  • ADTAA

Previous GeneCards Identifiers for AP2A1 Gene

  • GC19P050928
  • GC19P050638
  • GC19P054946
  • GC19P054961
  • GC19P050270
  • GC19P046646

Summaries for AP2A1 Gene

Entrez Gene Summary for AP2A1 Gene

  • 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]

GeneCards Summary for AP2A1 Gene

AP2A1 (Adaptor Related Protein Complex 2 Subunit Alpha 1) is a Protein Coding gene. Among its related pathways are Vesicle-mediated transport and Lipoprotein metabolism. Gene Ontology (GO) annotations related to this gene include binding and protein C-terminus binding. An important paralog of this gene is AP2A2.

UniProtKB/Swiss-Prot Summary for AP2A1 Gene

  • Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).

Gene Wiki entry for AP2A1 Gene

Additional gene information for AP2A1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AP2A1 Gene

Genomics for AP2A1 Gene

GeneHancer (GH) Regulatory Elements for AP2A1 Gene

Promoters and enhancers for AP2A1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around AP2A1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the AP2A1 gene promoter:
  • ARP-1
  • c-Ets-1
  • Egr-1
  • HOXA9
  • HOXA9B
  • Meis-1
  • Meis-1b
  • Olf-1
  • Pax-4a
  • Pax-5

Genomic Locations for AP2A1 Gene

Genomic Locations for AP2A1 Gene
chr19:49,766,923-49,807,113
(GRCh38/hg38)
Size:
40,191 bases
Orientation:
Plus strand
chr19:50,270,180-50,310,370
(GRCh37/hg19)
Size:
40,191 bases
Orientation:
Plus strand

Genomic View for AP2A1 Gene

Genes around AP2A1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AP2A1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AP2A1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AP2A1 Gene

Proteins for AP2A1 Gene

  • Protein details for AP2A1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95782-AP2A1_HUMAN
    Recommended name:
    AP-2 complex subunit alpha-1
    Protein Accession:
    O95782
    Secondary Accessions:
    • Q96CI7
    • Q96PP6
    • Q96PP7
    • Q9H070

    Protein attributes for AP2A1 Gene

    Size:
    977 amino acids
    Molecular mass:
    107546 Da
    Quaternary structure:
    • Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Interacts with SGIP1 (By similarity). Interacts with HIP1 and RAB11FIP2 (PubMed:11532990, PubMed:12364336). Interacts with SLC12A5 (By similarity). Interacts with clathrin (By similarity). Interacts with RFTN1 (PubMed:27022195). Interacts with KIAA1107 (PubMed:29262337). Interacts with PICALM (PubMed:16262731). Together with AP2B1 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497).
    SequenceCaution:
    • Sequence=AAD15564.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Alternative splice isoforms for AP2A1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for AP2A1 Gene

Post-translational modifications for AP2A1 Gene

  • Ubiquitination at Lys165, Lys880, and Lys891
  • Modification sites at PhosphoSitePlus

Other Protein References for AP2A1 Gene

No data available for DME Specific Peptides for AP2A1 Gene

Domains & Families for AP2A1 Gene

Suggested Antigen Peptide Sequences for AP2A1 Gene

GenScript: Design optimal peptide antigens:
  • Plasma membrane adaptor HA2/AP2 adaptin alpha A subunit (AP2A1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95782

UniProtKB/Swiss-Prot:

AP2A1_HUMAN :
  • Belongs to the adaptor complexes large subunit family.
Family:
  • Belongs to the adaptor complexes large subunit family.
genes like me logo Genes that share domains with AP2A1: view

Function for AP2A1 Gene

Molecular function for AP2A1 Gene

UniProtKB/Swiss-Prot Function:
Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).

Phenotypes From GWAS Catalog for AP2A1 Gene

Gene Ontology (GO) - Molecular Function for AP2A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16262731
GO:0008022 protein C-terminus binding IEA --
GO:0019901 protein kinase binding IEA,ISS --
GO:0035615 contributes_to clathrin adaptor activity TAS 12121421
GO:0044877 protein-containing complex binding IEA --
genes like me logo Genes that share ontologies with AP2A1: view
genes like me logo Genes that share phenotypes with AP2A1: view

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for AP2A1 Gene

Localization for AP2A1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for AP2A1 Gene

Cell membrane. Membrane, coated pit; Peripheral membrane protein; Cytoplasmic side. Note=AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for AP2A1 gene
Compartment Confidence
plasma membrane 5
golgi apparatus 5
endosome 4
cytosol 4
lysosome 4
nucleus 1
cytoskeleton 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for AP2A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
GO:0005905 clathrin-coated pit IEA --
GO:0016020 membrane HDA,IEA 19946888
GO:0016323 basolateral plasma membrane IEA --
genes like me logo Genes that share ontologies with AP2A1: view

Pathways & Interactions for AP2A1 Gene

genes like me logo Genes that share pathways with AP2A1: view

Gene Ontology (GO) - Biological Process for AP2A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006886 intracellular protein transport NAS 12036598
GO:0006895 Golgi to endosome transport NAS 12036598
GO:0006897 endocytosis NAS 12036598
GO:0010976 positive regulation of neuron projection development IEA --
GO:0015031 protein transport IEA --
genes like me logo Genes that share ontologies with AP2A1: view

No data available for SIGNOR curated interactions for AP2A1 Gene

Drugs & Compounds for AP2A1 Gene

No Compound Related Data Available

Transcripts for AP2A1 Gene

mRNA/cDNA for AP2A1 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for AP2A1 Gene

No ASD Table

Relevant External Links for AP2A1 Gene

GeneLoc Exon Structure for
AP2A1
ECgene alternative splicing isoforms for
AP2A1

Expression for AP2A1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for AP2A1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for AP2A1 Gene

This gene is overexpressed in Frontal cortex (10.1) and Brain (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for AP2A1 Gene



Protein tissue co-expression partners for AP2A1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of AP2A1 Gene:

AP2A1

SOURCE GeneReport for Unigene cluster for AP2A1 Gene:

Hs.467125

mRNA Expression by UniProt/SwissProt for AP2A1 Gene:

O95782-AP2A1_HUMAN
Tissue specificity: Expressed in the brain (at protein level) (PubMed:23676497). Isoform A: Expressed in forebrain, skeletal muscle, spinal cord, cerebellum, salivary gland, heart and colon. Isoform B: Widely expressed in tissues and also in breast cancer and in prostate carcinoma cells.

Evidence on tissue expression from TISSUES for AP2A1 Gene

  • Liver(4.4)
  • Muscle(4.3)
  • Nervous system(3.1)
  • Eye(2.4)
  • Adrenal gland(2.2)
  • Heart(2.1)
genes like me logo Genes that share expression patterns with AP2A1: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for AP2A1 Gene

Orthologs for AP2A1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for AP2A1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia AP2A1 33 32
  • 95.58 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia AP2A1 33
  • 94 (a)
OneToOne
cow
(Bos Taurus)
Mammalia AP2A1 33 32
  • 92.98 (n)
OneToOne
dog
(Canis familiaris)
Mammalia AP2A1 33 32
  • 92.74 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia AP2A1 33
  • 91 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ap2a1 17 33 32
  • 89.76 (n)
rat
(Rattus norvegicus)
Mammalia Ap2a1 32
  • 88.64 (n)
lizard
(Anolis carolinensis)
Reptilia AP2A1 33
  • 87 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ap2a1 32
  • 76.82 (n)
zebrafish
(Danio rerio)
Actinopterygii ap2a1 33 32
  • 75.89 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta alpha-Adaptin 33 34
  • 66 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea apa-2 33
  • 64 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes APL3 33
  • 24 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9573 33
  • 65 (a)
OneToMany
Cin.3545 32
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.3545 32
Species where no ortholog for AP2A1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for AP2A1 Gene

ENSEMBL:
Gene Tree for AP2A1 (if available)
TreeFam:
Gene Tree for AP2A1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AP2A1: view image

Paralogs for AP2A1 Gene

Paralogs for AP2A1 Gene

(1) SIMAP similar genes for AP2A1 Gene using alignment to 2 proteins:

  • AP2A1_HUMAN
  • M0R2D9_HUMAN
genes like me logo Genes that share paralogs with AP2A1: view

Variants for AP2A1 Gene

Sequence variations from dbSNP and Humsavar for AP2A1 Gene

SNP ID Clin Chr 19 pos Variation AA Info Type
rs137955120 risk-factor, Neural tube defects, susceptibility to 49,807,197(+) C/T downstream_transcript_variant
rs139365610 risk-factor, Neural tube defects, susceptibility to 49,807,348(+) C/A/T downstream_transcript_variant
rs1568595114 uncertain-significance, not provided 49,807,153(+) AAA/ downstream_transcript_variant
rs115945199 benign, not provided 49,807,170(+) G/T downstream_transcript_variant
rs1000002843 -- 49,780,492(+) G/A/C 5_prime_UTR_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for AP2A1 Gene

Variant ID Type Subtype PubMed ID
dgv53n68 CNV loss 17160897
esv3427277 CNV duplication 20981092
nsv1140251 OTHER inversion 24896259
nsv1160655 CNV deletion 26073780
nsv470150 CNV gain 18288195
nsv518114 CNV loss 19592680
nsv524546 CNV loss 19592680
nsv953600 CNV deletion 24416366
nsv9739 CNV gain+loss 18304495

Variation tolerance for AP2A1 Gene

Residual Variation Intolerance Score: 16.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.90; 35.37% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AP2A1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
AP2A1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AP2A1 Gene

Disorders for AP2A1 Gene

Additional Disease Information for AP2A1

No disorders were found for AP2A1 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for AP2A1 Gene

Publications for AP2A1 Gene

  1. The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. (PMID: 11532990) Waelter S … Wanker EE (Human molecular genetics 2001) 3 4 23 56
  2. Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease. (PMID: 23676497) Marcello E … Di Luca M (The Journal of clinical investigation 2013) 3 4 56
  3. Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome. (PMID: 18178234) Kitagawa Y … Ikuta K (Virology 2008) 3 23 56
  4. Effect of clathrin assembly lymphoid myeloid leukemia protein depletion on clathrin coat formation. (PMID: 16262731) Meyerholz A … Ungewickell EJ (Traffic (Copenhagen, Denmark) 2005) 3 4 56
  5. The DNA sequence and biology of human chromosome 19. (PMID: 15057824) Grimwood J … Lucas SM (Nature 2004) 3 4 56

Products for AP2A1 Gene

Sources for AP2A1 Gene