Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001648
UniProt IDO75581
Primary gene name(s)LRP6
Synonym gene name(s)unknown
Protein nameLow-density lipoprotein receptor-related protein 6
Protein functionComponent of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation, By similarity. {ECO:0000250, ECO:0000269|PubMed:11357136, ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:16341017, ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:17326769, ECO:0000269|PubMed:17400545, ECO:0000269|PubMed:19107203, ECO:0000269|PubMed:19293931, ECO:0000269|PubMed:19801552}.
Subcellular locationCell membrane {ECO:0000269|PubMed:26387593};
Single-pass type I membrane protein. Endoplasmic reticulum {ECO:0000269|PubMed:26387593}. Note=On Wnt signaling, undergoes a cycle of caveolin- or clathrin-mediated endocytosis and plasma membrane location. Released from the endoplasmic reticulum on palmitoylation. Mono-ubiquitination retains it in the endoplasmic reticulum in the absence of palmitoylation. On Wnt signaling, phosphorylated, aggregates and colocalizes with AXIN1 and GSK3B at the plasma membrane in LRP6-signalsomes. Chaperoned to the plasma membrane by MESD, By similarity. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O75581
Gene Ontology
(Biological Process)
Complete annatation
axis elongation involved in somitogenesis [GO:0090245];
beta-catenin destruction complex disassembly [GO:1904886];
canonical Wnt signaling pathway [GO:0060070];
canonical Wnt signaling pathway involved in neural crest cell differentiation [GO:0044335];
canonical Wnt signaling pathway involved in regulation of cell proliferation [GO:0044340];
cellular response to cholesterol [GO:0071397];
cerebellum morphogenesis [GO:0021587];
cerebral cortex development [GO:0021987];
chemical synaptic transmission [GO:0007268];
convergent extension [GO:0060026];
dopaminergic neuron differentiation [GO:0071542];
embryonic pattern specification [GO:0009880];
embryonic retina morphogenesis in camera-type eye [GO:0060059];
external genitalia morphogenesis [GO:0035261];
face morphogenesis [GO:0060325];
midbrain dopaminergic neuron differentiation [GO:1904948];
midbrain-hindbrain boundary development [GO:0030917];
negative regulation of canonical Wnt signaling pathway [GO:0090090];
negative regulation of protein kinase activity [GO:0006469];
negative regulation of protein phosphorylation [GO:0001933];
negative regulation of protein serine/threonine kinase activity [GO:0071901];
negative regulation of smooth muscle cell apoptotic process [GO:0034392];
neural crest cell differentiation [GO:0014033];
neural crest formation [GO:0014029];
neural tube closure [GO:0001843];
odontogenesis of dentin-containing tooth [GO:0042475];
palate development [GO:0060021];
pericardium morphogenesis [GO:0003344];
positive regulation of canonical Wnt signaling pathway [GO:0090263];
positive regulation of cell cycle [GO:0045787];
positive regulation of cytosolic calcium ion concentration [GO:0007204];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of Wnt signaling pathway involved in dorsal/ventral axis specification [GO:2000055];
primitive streak formation [GO:0090009];
protein localization to plasma membrane [GO:0072659];
receptor-mediated endocytosis involved in cholesterol transport [GO:0090118];
response to peptide hormone [GO:0043434];
single organismal cell-cell adhesion [GO:0016337];
thalamus development [GO:0021794];
trachea cartilage morphogenesis [GO:0060535];
Wnt signaling pathway [GO:0016055];
Wnt signaling pathway involved in dorsal/ventral axis specification [GO:0044332];
Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation [GO:1904953];
Wnt signaling pathway involved in somitogenesis [GO:0090244]
Gene Ontology
(Molecular Function)
Complete annatation
apolipoprotein binding [GO:0034185];
coreceptor activity involved in canonical Wnt signaling pathway [GO:1904928];
coreceptor activity involved in Wnt signaling pathway [GO:0071936];
frizzled binding [GO:0005109];
identical protein binding [GO:0042802];
kinase inhibitor activity [GO:0019210];
low-density lipoprotein receptor activity [GO:0005041];
protein homodimerization activity [GO:0042803];
receptor binding [GO:0005102];
toxin transporter activity [GO:0019534];
Wnt-activated receptor activity [GO:0042813];
Wnt-protein binding [GO:0017147]
Gene Ontology
(Cellular Component)
Complete annatation
cell surface [GO:0009986];
cytoplasmic vesicle [GO:0031410];
cytosol [GO:0005829];
early endosome membrane [GO:0031901];
endoplasmic reticulum [GO:0005783];
extracellular region [GO:0005576];
integral component of membrane [GO:0016021];
neuronal cell body [GO:0043025];
plasma membrane [GO:0005886];
receptor complex [GO:0043235];
synapse [GO:0045202];
Wnt-Frizzled-LRP5/6 complex [GO:1990851];
Wnt signalosome [GO:1990909]
Protein-protein interaction110219
Phylogenetic treeO75581
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. CD3-0.6025395859541130.2225139071734270.331199842871608
AZA vs. DISU-0.3335023384869830.575661476044150.954304256505839
AZA vs. IL7-0.2899184775518490.5698868576579280.999311006273513
AZA vs. SAHA0.3649854664518480.4775175078619930.808230284472455
DISU vs. CD30.2544856767677540.613642012351220.722553531363916
DISU vs. IL70.03610337064439770.9444563775518110.99026223704605
DISU vs. SAHA0.6986802684920570.1824711267129160.547922365150501
DMSO vs. AZA-0.1125258142598660.8445616400412261
DMSO vs. CD30.4697544386260780.3120285125207320.423785326504146
DMSO vs. DISU0.2166270979596190.7072531038432050.960763093481455
DMSO vs. IL7-0.1679367945055740.7309800014652590.946044258421083
DMSO vs. SAHA0.4722447196582190.3372311103083170.690469938621548
HIV vs. Mock in Activation-0.81980330831940.2295420570926050.999983755607037
HIV vs. Mock in Latency-0.5532496854045410.2807991559256430.999834320637052
IL7 vs. CD30.3176708989906930.40439607889660.541674406576775
SAHA vs. CD30.938013148195630.01564332220023290.0374138812184589
SAHA vs. IL70.6496519991965950.1150613156325910.312341846181466
(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 -0.457312 0.000839432
(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
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3S2K X-ray 2.8Å A/B=630-1246.
3S8V X-ray 3.1Å A/B=629-1243.
3S8Z X-ray 2.8Å A=629-1243.
3S94 X-ray 2.8Å A/B=20-630.
3SOB X-ray 1.9Å B=20-335.
3SOQ X-ray 1.9Å A=20-326.
3SOV X-ray 1.2Å A=20-326.
4A0P X-ray 1.9Å A=629-1244.
4DG6 X-ray 2.9Å A=20-635.
4NM5 X-ray 2.3Å C=1568-1575.
4NM7 X-ray 2.3Å C=1603-1610.
5AIR X-ray 2.5Å A/B=1565-1575.
5FWW X-ray 3.5Å A=630-1246.

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)