Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003132
UniProt IDQ14669
Primary gene name(s)TRIP12
Synonym gene name(s)KIAA0045, ULF
Protein nameE3 ubiquitin-protein ligase TRIP12
Protein functionE3 ubiquitin-protein ligase involved in ubiquitin fusion degradation, UFD pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation, UFD pathway, a process that mediates ubiquitination of protein at their N-terminus, regardeless of the presence of lysine residues in target proteins. In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation. Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation. Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins. Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692}.
Subcellular locationNucleus, nucleoplasm {ECO:0000269|PubMed:20208519}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q14669
Gene Ontology
(Biological Process)
Complete annatation
cellular response to DNA damage stimulus [GO:0006974];
DNA repair [GO:0006281];
embryo development [GO:0009790];
negative regulation of double-strand break repair [GO:2000780];
negative regulation of histone H2A K63-linked ubiquitination [GO:1901315];
protein polyubiquitination [GO:0000209];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787]
Gene Ontology
(Molecular Function)
Complete annatation
ligase activity [GO:0016874];
thyroid hormone receptor binding [GO:0046966];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction114731
Phylogenetic treeQ14669
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD30.7339093031128950.02550033101282080.0568972596632472
AZA vs. DISU0.115465671635790.6473558669859190.960057478314726
AZA vs. IL70.1300620652489160.4976460481285660.999311006273513
AZA vs. SAHA-0.09997430694716480.6813999772599970.907389764583217
DISU vs. CD3-0.6311652542414630.08225857049263320.159954294582811
DISU vs. IL70.00556978073660480.9823244669590440.997754944136459
DISU vs. SAHA-0.2141991127235530.4617344803678290.800119649301005
DMSO vs. AZA-0.03531230074503590.832505847028791
DMSO vs. CD3-0.77913453424680.0152694364576080.0356586669096055
DMSO vs. DISU-0.1522891939316130.5317154031868770.918916413535118
DMSO vs. IL70.1724585624872730.3362270768633760.807640433491467
DMSO vs. SAHA-0.07213957680528730.7591217206554210.930297284308295
HIV vs. Mock in Activation0.2034788874479640.7444992615973060.999983755607037
HIV vs. Mock in Latency0.1100388642570820.5036891276513140.999834320637052
IL7 vs. CD3-0.596149591375550.06414161642917620.1342414030043
SAHA vs. CD3-0.8589537260208010.01567397566401220.0374634120946334
SAHA vs. IL7-0.2337225975865920.3363351976290450.586728014009979
(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 -0.523177 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
0.883 0.971 1.036 1.121 1.045
(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

not found

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
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
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