Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008517
UniProt IDQ96PU5
Primary gene name(s)NEDD4L
Synonym gene name(s)KIAA0439, NEDL3
Protein nameE3 ubiquitin-protein ligase NEDD4-like
Protein functionE3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1, PubMed:25631046. Plays a role in dendrite formation by melanocytes, PubMed:23999003. {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15489223, ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:15576372, ECO:0000269|PubMed:19144635, ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:25631046}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:18819914}. Note=May be recruited to exosomes by NDFIP1.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q96PU5
Gene Ontology
(Biological Process)
Complete annatation
cellular sodium ion homeostasis [GO:0006883];
excretion [GO:0007588];
ion transmembrane transport [GO:0034220];
negative regulation of potassium ion transmembrane transport [GO:1901380];
negative regulation of potassium ion transmembrane transporter activity [GO:1901017];
negative regulation of protein localization to cell surface [GO:2000009];
negative regulation of sodium ion transmembrane transport [GO:1902306];
negative regulation of sodium ion transmembrane transporter activity [GO:2000650];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
positive regulation of caveolin-mediated endocytosis [GO:2001288];
positive regulation of dendrite extension [GO:1903861];
positive regulation of endocytosis [GO:0045807];
positive regulation of protein catabolic process [GO:0045732];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein K48-linked ubiquitination [GO:0070936];
protein monoubiquitination [GO:0006513];
protein polyubiquitination [GO:0000209];
protein ubiquitination [GO:0016567];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of ion transmembrane transport [GO:0034765];
regulation of membrane depolarization [GO:0003254];
regulation of membrane potential [GO:0042391];
regulation of membrane repolarization [GO:0060306];
regulation of potassium ion transmembrane transporter activity [GO:1901016];
regulation of protein catabolic process [GO:0042176];
response to metal ion [GO:0010038];
sodium ion transport [GO:0006814];
ventricular cardiac muscle cell action potential [GO:0086005];
viral life cycle [GO:0019058];
water homeostasis [GO:0030104]
Gene Ontology
(Molecular Function)
Complete annatation
ion channel binding [GO:0044325];
ligase activity [GO:0016874];
potassium channel inhibitor activity [GO:0019870];
potassium channel regulator activity [GO:0015459];
sodium channel inhibitor activity [GO:0019871];
sodium channel regulator activity [GO:0017080];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
intracellular [GO:0005622];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction116915
Phylogenetic treeQ96PU5
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. CD3-1.055454147947480.01627284240444830.039324078999494
AZA vs. DISU0.2137821781399760.7065982024348410.972007784586858
AZA vs. IL70.4257381652137110.2717957179696550.999311006273513
AZA vs. SAHA-0.5628569196892150.1713720372877180.528033920619972
DISU vs. CD31.257006795060070.02334126082300170.0584753474565278
DISU vs. IL70.2025247953511940.689772603348260.918423821203107
DISU vs. SAHA-0.774164161136360.1530919282859770.502997264268139
DMSO vs. AZA0.02039275519208760.9638192986729311
DMSO vs. CD31.066751518325580.01166232718631350.028429281401588
DMSO vs. DISU-0.1943776720213590.7262954024501410.964942874095702
DMSO vs. IL70.4121724756676440.2593985926525450.761564269915705
DMSO vs. SAHA-0.5892052167899550.1322466716781240.436029225303217
HIV vs. Mock in Activation0.7406844506076710.2401489274681930.999983755607037
HIV vs. Mock in Latency0.435374876824630.01318269961237130.395848633380249
IL7 vs. CD31.487064427016788.26787750018987e-066.54182244411348e-05
SAHA vs. CD30.4699274328229050.1936281609931760.294536831146378
SAHA vs. IL7-0.9920159563650190.0006763933393333370.0086406383026362
(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
-1.028 0.008426

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) unknown
(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 0.294082 0.447422
(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
2LAJ NMR - A=496-535.
2LB2 NMR - A=386-420.
2LTY NMR - A=385-417.
2MPT NMR - A=496-539# B=945-957.
2NSQ X-ray 1.8Å A=1-154.
2ONI X-ray 2.2Å A=594-967.
3JVZ X-ray 3.3Å C/D=596-975.
3JW0 X-ray 3.1Å C/D=596-975.
5HPK X-ray 2.4Å A=594-975.

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

HIV Partner Interaction Type PubMed
Vpr interacts with 22190034
Pr55(Gag) binds 25633977
p6 interacts with 18321968
Pr55(Gag) associates with 20862313
Pr55(Gag) regulated by 25633977
nucleocapsid rescued by 21159863
Pr55(Gag) rescued by 20862313

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04530 Tight junction - Homo sapiens (human)
hsa04960 Aldosterone-regulated sodium reabsorption - Homo sapiens (human)