Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001385
UniProt IDQ7Z6Z7
Primary gene name(s)HUWE1
Synonym gene name(s)KIAA0312, KIAA1578, UREB1
Protein nameE3 ubiquitin-protein ligase HUWE1
Protein functionE3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1. Mediates monoubiquitination of DNA polymerase beta, POLB at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair. Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4. Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN. May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation. Mediates polyubiquitination of isoform 2 of PA2G4. {ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:19713937}. Nucleus {ECO:0000269|PubMed:19713937}. Note=Mainly expressed in the cytoplasm of most tissues, except in the nucleus of spermatogonia, primary spermatocytes and neuronal cells, By similarity. Predominantly cytosolic or perinuclear in some colorectal carcinoma cells. {ECO:0000250|UniProtKB:Q7TMY8}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q7Z6Z7
Gene Ontology
(Biological Process)
Complete annatation
base-excision repair [GO:0006284];
cell differentiation [GO:0030154];
histone ubiquitination [GO:0016574];
positive regulation of protein targeting to mitochondrion [GO:1903955];
protein monoubiquitination [GO:0006513];
protein polyubiquitination [GO:0000209];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787]
Gene Ontology
(Molecular Function)
Complete annatation
DNA binding [GO:0003677];
ligase activity [GO:0016874];
poly(A RNA binding [GO:0044822];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
membrane [GO:0016020];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction115385
Phylogenetic treeQ7Z6Z7
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. CD30.9082968931618150.005990882243194440.0168964403385903
AZA vs. DISU0.2734392927940940.2790696861989190.849494436543318
AZA vs. IL70.07616416981699380.6908888795690210.999311006273513
AZA vs. SAHA0.2250502903156330.3553866720011360.724581811856781
DISU vs. CD3-0.6480977828253980.07466972817237260.148335725154236
DISU vs. IL7-0.2065738734472810.4115503819401920.770315620529972
DISU vs. SAHA-0.04573808511573480.8749689435457080.967472996931575
DMSO vs. AZA0.123248178828350.4599569634188331
DMSO vs. CD3-0.7950781591881660.01380210127763580.0327395143674356
DMSO vs. DISU-0.1517312462416930.533720973873320.920138379427847
DMSO vs. IL7-0.0399304422039970.8235966660582840.963051812112721
DMSO vs. SAHA0.09548767835810880.6851296706020930.901903272327721
HIV vs. Mock in Activation0.2847901985002060.6489651104294690.999983755607037
HIV vs. Mock in Latency0.1204870963321290.4637227786791890.999834320637052
IL7 vs. CD3-0.82593455187420.01081501493113980.0318574790027497
SAHA vs. CD3-0.7068620238253790.04623614037738770.0929038180649643
SAHA vs. IL70.1459572135828420.5482607530249790.761984380518028
(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 -0.0900922 0.775331
(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
1.03 0.981 0.981 0.919 1.072
(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
2EKK NMR - A=1317-1356.
2MUL NMR - A=2951-3003.
3G1N X-ray 2.6Å A/B=4005-4374.
3H1D X-ray 1.8Å A=3993-4374.
5C6H X-ray 2.0Å B/D/F/H/J/L/N/P/R/T/V/X=1969-1994.

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

HIV Partner Interaction Type PubMed
Rev interacts with 22174317
integrase interacts with 21167302
retropepsin cleaves 22944692
Gag-Pol interacts with 21167302
Vif interacts with 22190034
HIV-1 virus replication enhanced by expression of human gene 18187620

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)