Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003218
UniProt IDQ9UMX0
Primary gene name(s)UBQLN1
Synonym gene name(s)DA41, PLIC1
Protein nameUbiquilin-1
Protein functionPlays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system, UPS, autophagy and endoplasmic reticulum-associated protein degradation, ERAD pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding, via UBA domain to their polyubiquitin chains and by interacting, via ubiquitin-like domain with the subunits of the proteasome, PubMed:15147878. Plays a role in the ERAD pathway via its interaction with ER-localized proteins UBXN4, VCP and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome, PubMed:19822669, PubMed:18307982. Isoform 1, isoform 2 and isoform 3 play a role in unfolded protein response, UPR by attenuating the induction of UPR-inducible genes, DDTI3/CHOP, HSPA5 and PDIA2 during ER stress, PubMed:18953672. Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy-related protein LC3 from the cytosolic form LC3-I to the membrane-bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion, PubMed:19148225, PubMed:20529957, PubMed:23459205. Negatively regulates the TICAM1/TRIF-dependent toll-like receptor signaling pathway by decreasing the abundance of TICAM1 via the autophagic pathway, PubMed:21695056. Isoform 1 and isoform 3 play a key role in the regulation of the levels of PSEN1 by targeting its accumulation to aggresomes which may then be removed from cells by autophagocytosis, PubMed:21143716. Promotes the ubiquitination and lysosomal degradation of ORAI1, consequently downregulating the ORAI1-mediated Ca2+ mobilization, PubMed:23307288. Suppresses the maturation and proteasomal degradation of amyloid beta A4 protein, A4 by stimulating the lysine 63, K63-linked polyubiquitination. Delays the maturation of A4 by sequestering it in the Golgi apparatus and preventing its transport to the cell surface for subsequent processing, By similarity. {ECO:0000250|UniProtKB:Q9JJP9, ECO:0000269|PubMed:18307982, ECO:0000269|PubMed:18953672, ECO:0000269|PubMed:19148225, ECO:0000269|PubMed:19822669, ECO:0000269|PubMed:20529957, ECO:0000269|PubMed:21143716, ECO:0000269|PubMed:21695056, ECO:0000269|PubMed:23307288, ECO:0000269|PubMed:23459205, ECO:0000303|PubMed:15147878}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:16159959, ECO:0000269|PubMed:23979357}. Nucleus {ECO:0000269|PubMed:23979357}. Endoplasmic reticulum {ECO:0000269|PubMed:19822669}. Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:19148225, ECO:0000269|PubMed:20529957, ECO:0000269|PubMed:21143716, ECO:0000269|PubMed:21695056, ECO:0000269|PubMed:23307288, ECO:0000269|PubMed:23459205}. Cell membrane {ECO:0000269|PubMed:21143716, ECO:0000269|PubMed:23307288}. Note=Detected in neuronal processes and at synapses, By similarity. Recruited to the ER during ER-associated protein degradation, ERAD, PubMed:19822669. Isoform 1 and isoform 3 colocalize with PSEN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes, PubMed:21143716. Colocalizes with ORAI1 and TICAM1 in the autophagosome, PubMed:23307288, PubMed:21695056. Colocalizes with EPS15 and HGS in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments and with EPS15 also in aggresomes, PubMed:16159959. {ECO:0000250|UniProtKB:Q9JJP9, ECO:0000269|PubMed:16159959, ECO:0000269|PubMed:19822669, ECO:0000269|PubMed:21143716, ECO:0000269|PubMed:21695056, ECO:0000269|PubMed:23307288}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9UMX0
Gene Ontology
(Biological Process)
Complete annatation
aggrephagy [GO:0035973];
autophagosome assembly [GO:0000045];
autophagosome maturation [GO:0097352];
cellular response to hypoxia [GO:0071456];
ER-associated ubiquitin-dependent protein catabolic process [GO:0030433];
macroautophagy [GO:0016236];
negative regulation of store-operated calcium channel activity [GO:1901340];
negative regulation of toll-like receptor 3 signaling pathway [GO:0034140];
positive regulation of ER-associated ubiquitin-dependent protein catabolic process [GO:1903071];
positive regulation of protein ubiquitination [GO:0031398];
regulation of oxidative stress-induced intrinsic apoptotic signaling pathway [GO:1902175];
regulation of protein ubiquitination [GO:0031396];
response to endoplasmic reticulum stress [GO:0034976]
Gene Ontology
(Molecular Function)
Complete annatation
identical protein binding [GO:0042802];
kinase binding [GO:0019900];
polyubiquitin binding [GO:0031593]
Gene Ontology
(Cellular Component)
Complete annatation
aggresome [GO:0016235];
autophagosome [GO:0005776];
cytoplasm [GO:0005737];
cytoplasmic vesicle [GO:0031410];
endoplasmic reticulum [GO:0005783];
nucleoplasm [GO:0005654];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
proteasome complex [GO:0000502];
protein complex [GO:0043234]
Protein-protein interaction119007
Phylogenetic treeQ9UMX0
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. CD30.7723475766358030.01884397310935550.0443221539800571
AZA vs. DISU0.2054000532901460.416580487100860.911342924190573
AZA vs. IL70.2369591045875120.2169882149390520.98382931294628
AZA vs. SAHA0.03706424975225620.8790510414950020.97315727227035
DISU vs. CD3-0.5799660281790940.1110220975209060.202388087801443
DISU vs. IL70.02265086986593920.9282700141148210.986511840872818
DISU vs. SAHA-0.1672192906447350.5662927948993610.859562766837372
DMSO vs. AZA-0.07425048582686810.6569431355764471
DMSO vs. CD3-0.8571330724335380.007720284773736540.0199324918794072
DMSO vs. DISU-0.2813780546812320.2485415387041010.767598853546516
DMSO vs. IL70.3184701045005290.07618108371228150.5210661692208
DMSO vs. SAHA0.1039658772606580.6588849021138650.892524396635398
HIV vs. Mock in Activation0.05045820365466680.93529524909740.999983755607037
HIV vs. Mock in Latency-0.03163577397775140.8477329569260930.999834320637052
IL7 vs. CD3-0.5274100716992690.1011300339735980.191691775916001
SAHA vs. CD3-0.7607024433036020.03194394534138580.0683314771177692
SAHA vs. IL7-0.2037014291220340.4023748776833840.648996226758157
(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 -0.00311239 0.987278
(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
1.036 0.977 0.951 0.98 0.943
(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
2JY5 NMR - A=541-586.
2JY6 NMR - B=541-586.
2KLC NMR - A=34-112.

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
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)