Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000113
UniProt IDO94973
Primary gene name(s)AP2A2
Synonym gene name(s)ADTAB, CLAPA2, HIP9, HYPJ, KIAA0899
Protein nameAP-2 complex subunit alpha-2
Protein functionComponent 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. 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. {ECO:0000250, ECO:0000269|PubMed:12960147, ECO:0000269|PubMed:14745134, ECO:0000269|PubMed:15473838, ECO:0000269|PubMed:19033387}.
Subcellular locationCell membrane {ECO:0000250|UniProtKB:P17427};
Peripheral membrane protein {ECO:0000250|UniProtKB:P17427};
Cytoplasmic side {ECO:0000250|UniProtKB:P17427}. Membrane, coated pit {ECO:0000250|UniProtKB:P17427};
Peripheral membrane protein {ECO:0000250|UniProtKB:P17427};
Cytoplasmic side {ECO:0000250|UniProtKB:P17427}. 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|UniProtKB:P17427}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O94973
Gene Ontology
(Biological Process)
Complete annatation
antigen processing and presentation of exogenous peptide antigen via MHC class II [GO:0019886];
clathrin-dependent endocytosis [GO:0072583];
ephrin receptor signaling pathway [GO:0048013];
intracellular protein transport [GO:0006886];
microtubule-based movement [GO:0007018];
negative regulation of epidermal growth factor receptor signaling pathway [GO:0042059];
regulation of defense response to virus by virus [GO:0050690];
Wnt signaling pathway, planar cell polarity pathway [GO:0060071]
Gene Ontology
(Molecular Function)
Complete annatation
lipid binding [GO:0008289];
protein kinase binding [GO:0019901];
protein transporter activity [GO:0008565]
Gene Ontology
(Cellular Component)
Complete annatation
AP-2 adaptor complex [GO:0030122];
clathrin-coated endocytic vesicle membrane [GO:0030669];
cytoplasmic, membrane-bounded vesicle [GO:0016023];
cytosol [GO:0005829];
endocytic vesicle membrane [GO:0030666];
endolysosome membrane [GO:0036020];
plasma membrane [GO:0005886]
Protein-protein interaction106670
Phylogenetic treeO94973
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-0.5976677774219250.06935344267534870.130287309984153
AZA vs. DISU0.04072992949173670.872202572794430.991631204917382
AZA vs. IL7-0.07532920070822380.6962137712200890.999311006273513
AZA vs. SAHA0.04574351328211470.8514781309884830.965051229061684
DISU vs. CD30.625413558190070.08581424643068680.16548048416041
DISU vs. IL7-0.1253406757215670.6193012184090810.88509594810144
DISU vs. SAHA0.007380433296053770.9797967629708070.996391161587924
DMSO vs. AZA0.05184311269390440.7581068240072221
DMSO vs. CD30.635487677646870.04844508219812340.0937837526747274
DMSO vs. DISU0.0085697552314780.972021712093070.995077522347534
DMSO vs. IL7-0.1194570448537870.5079078422435140.887649119764145
DMSO vs. SAHA-0.01115587621004820.9623309078632190.991813520646008
HIV vs. Mock in Activation0.092150445032420.8823656322842720.999983755607037
HIV vs. Mock in Latency-0.08380897567589230.6127985894614190.999834320637052
IL7 vs. CD30.5286482854938320.1018241935295560.192728603950735
SAHA vs. CD30.6192889876020720.08094658043161570.146883198928892
SAHA vs. IL70.1179339660956480.6288900747519750.815637029511593
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.372007 0.00764092
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.002 1.002 1.095 1.251 1.127
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Pr55(Gag) binds 16139856
Nef binds 18032517
Envelope transmembrane glycoprotein gp41 interacts with 17108326
Nef inhibited by 17581864
Nef requires 25496667
Envelope transmembrane glycoprotein gp41 requires 26269175
Tat interacts with 15020715

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04144 Endocytosis - Homo sapiens (human)
hsa04721 Synaptic vesicle cycle - Homo sapiens (human)
hsa04961 Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human)
hsa05016 Huntington's disease - Homo sapiens (human)