Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000124
UniProt IDP05067
Primary gene name(s)APP
Synonym gene name(s)A4, AD1
Protein nameAmyloid beta A4 protein
Protein functionFunctions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O and JIP. Inhibits G(o alpha ATPase activity, By similarity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+ ions for GPC1 which are required for release of nitric oxide, NO and subsequent degradation of the heparan sulfate chains on GPC1. {ECO:0000250}.; FUNCTION: Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+ and Fe(3+ to Cu(+ and Fe(2+, respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.; FUNCTION: Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. {ECO:0000250}.; FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.; FUNCTION: N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies, via caspase-3 and axons, via caspase-6.
Subcellular locationMembrane;
Single-pass type I membrane protein. Membrane, clathrin-coated pit. Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. During maturation, the immature APP, N-glycosylated in the endoplasmic reticulum moves to the Golgi complex where complete maturation occurs, O-glycosylated and sulfated. After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. Gamma-CTF(59 peptide is located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1, Fe65. Beta-APP42 associates with FRPL1 at the cell surface and the complex is then rapidly internalized. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body. Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P05067
Gene Ontology
(Biological Process)
Complete annatation
adult locomotory behavior [GO:0008344];
amyloid fibril formation [GO:1990000];
antibacterial humoral response [GO:0019731];
antifungal humoral response [GO:0019732];
axo-dendritic transport [GO:0008088];
axon midline choice point recognition [GO:0016199];
axonogenesis [GO:0007409];
cell adhesion [GO:0007155];
cellular copper ion homeostasis [GO:0006878];
cellular process [GO:0009987];
cellular protein metabolic process [GO:0044267];
cellular response to cAMP [GO:0071320];
cellular response to nerve growth factor stimulus [GO:1990090];
cellular response to norepinephrine stimulus [GO:0071874];
cholesterol metabolic process [GO:0008203];
collateral sprouting in absence of injury [GO:0048669];
defense response to Gram-negative bacterium [GO:0050829];
defense response to Gram-positive bacterium [GO:0050830];
dendrite development [GO:0016358];
endocytosis [GO:0006897];
extracellular matrix organization [GO:0030198];
forebrain development [GO:0030900];
innate immune response [GO:0045087];
ionotropic glutamate receptor signaling pathway [GO:0035235];
locomotory behavior [GO:0007626];
mating behavior [GO:0007617];
mRNA polyadenylation [GO:0006378];
negative regulation of neuron differentiation [GO:0045665];
neuromuscular process controlling balance [GO:0050885];
neuron apoptotic process [GO:0051402];
neuron projection development [GO:0031175];
neuron remodeling [GO:0016322];
Notch signaling pathway [GO:0007219];
platelet degranulation [GO:0002576];
positive regulation of G2/M transition of mitotic cell cycle [GO:0010971];
positive regulation of mitotic cell cycle [GO:0045931];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
protein phosphorylation [GO:0006468];
regulation of epidermal growth factor-activated receptor activity [GO:0007176];
regulation of multicellular organism growth [GO:0040014];
regulation of protein binding [GO:0043393];
regulation of synapse structure or activity [GO:0050803];
regulation of translation [GO:0006417];
response to lead ion [GO:0010288];
response to oxidative stress [GO:0006979];
response to yeast [GO:0001878];
smooth endoplasmic reticulum calcium ion homeostasis [GO:0051563];
suckling behavior [GO:0001967];
synaptic growth at neuromuscular junction [GO:0051124];
visual learning [GO:0008542]
Gene Ontology
(Molecular Function)
Complete annatation
acetylcholine receptor binding [GO:0033130];
DNA binding [GO:0003677];
enzyme binding [GO:0019899];
heparin binding [GO:0008201];
identical protein binding [GO:0042802];
peptidase activator activity [GO:0016504];
PTB domain binding [GO:0051425];
receptor binding [GO:0005102];
serine-type endopeptidase inhibitor activity [GO:0004867];
transition metal ion binding [GO:0046914]
Gene Ontology
(Cellular Component)
Complete annatation
apical part of cell [GO:0045177];
astrocyte projection [GO:0097449];
axon [GO:0030424];
cell-cell junction [GO:0005911];
cell surface [GO:0009986];
ciliary rootlet [GO:0035253];
coated pit [GO:0005905];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
dendritic shaft [GO:0043198];
dendritic spine [GO:0043197];
endosome [GO:0005768];
endosome lumen [GO:0031904];
ER to Golgi transport vesicle [GO:0030134];
extracellular exosome [GO:0070062];
extracellular region [GO:0005576];
extracellular space [GO:0005615];
Golgi apparatus [GO:0005794];
growth cone filopodium [GO:1990812];
growth cone lamellipodium [GO:1990761];
integral component of membrane [GO:0016021];
integral component of plasma membrane [GO:0005887];
intracellular membrane-bounded organelle [GO:0043231];
main axon [GO:0044304];
membrane raft [GO:0045121];
neuromuscular junction [GO:0031594];
nuclear envelope lumen [GO:0005641];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
platelet alpha granule lumen [GO:0031093];
receptor complex [GO:0043235];
rough endoplasmic reticulum [GO:0005791];
smooth endoplasmic reticulum [GO:0005790];
spindle midzone [GO:0051233];
synapse [GO:0045202];
terminal bouton [GO:0043195];
trans-Golgi network membrane [GO:0032588]
Protein-protein interaction106848
Phylogenetic treeP05067
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. CD30.596226011861460.203700324696560.309322191636377
AZA vs. DISU-0.3158460178741170.2125656425429950.801649999689472
AZA vs. IL7-0.01340591014733130.9443986560278120.999311006273513
AZA vs. SAHA0.5119157066713810.0364546607329370.223927284388057
DISU vs. CD3-0.9231764222639160.06778113757827970.137792699643289
DISU vs. IL70.2926153521431720.246507358537530.632732648946835
DISU vs. SAHA0.8294451081253020.004883853666608150.0635617949995263
DMSO vs. AZA-0.002505188522054490.9880687622064631
DMSO vs. CD3-0.6082982268496130.2009217837329460.300226807373223
DMSO vs. DISU0.3117898185005840.2019280844681810.717776976395015
DMSO vs. IL7-0.003673311301687870.9836990861250550.998221026906907
DMSO vs. SAHA0.5079672833281890.03176415398144160.191793896095475
HIV vs. Mock in Activation0.1771065621102650.8606636344740160.999983755607037
HIV vs. Mock in Latency0.1738113590560970.3703141952369840.999834320637052
IL7 vs. CD3-0.6036481553865270.1927732487071480.313550359098181
SAHA vs. CD3-0.1081680300888810.8147089338551510.868415874465775
SAHA vs. IL70.5225640424692930.03233972168215360.137436979034898
(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) FALSE
(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 2.14228 0.000305467
(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
unknown unknown unknown unknown unknown
(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