Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000148
UniProt IDO95376
Primary gene name(s)ARIH2
Synonym gene name(s)ARI2, TRIAD1
Protein nameE3 ubiquitin-protein ligase ARIH2
Protein functionE3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3, PubMed:16118314, PubMed:17646546, PubMed:19340006, PubMed:24076655. Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-5-RING ubiquitin ligase complex, ECS complex, also named CRL5 complex and initiating ubiquitination of ECS substrates: associates with ECS complex and specifically mediates addition of the first ubiquitin on ECS targets, By similarity. The initial ubiquitin is then elongated, By similarity. E3 ubiquitin-protein ligase activity is activated upon binding to neddylated form of the ECS complex, PubMed:24076655. Mediates 'Lys-6', 'Lys-48'-and 'Lys-63'-linked polyubiquitination, PubMed:16118314, PubMed:17646546, PubMed:19340006. May play a role in myelopoiesis, PubMed:19340006. {ECO:0000250|UniProtKB:Q9Y4X5, ECO:0000269|PubMed:16118314, ECO:0000269|PubMed:17646546, ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:24076655}.
Subcellular locationNucleus {ECO:0000269|PubMed:16118314}. Cytoplasm {ECO:0000269|PubMed:19340006}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O95376
Gene Ontology
(Biological Process)
Complete annatation
developmental cell growth [GO:0048588];
hematopoietic stem cell proliferation [GO:0071425];
multicellular organism development [GO:0007275];
positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436];
positive regulation of protein targeting to mitochondrion [GO:1903955];
protein K48-linked ubiquitination [GO:0070936];
protein K63-linked ubiquitination [GO:0070534];
protein polyubiquitination [GO:0000209];
protein ubiquitination [GO:0016567];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787]
Gene Ontology
(Molecular Function)
Complete annatation
ligase activity [GO:0016874];
ubiquitin conjugating enzyme binding [GO:0031624];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
nucleus [GO:0005634];
ubiquitin ligase complex [GO:0000151]
Protein-protein interaction115694
Phylogenetic treeO95376
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. CD30.5568394155395490.09000003732006190.161521552044013
AZA vs. DISU0.05521572710521530.8269961537160090.985239814541943
AZA vs. IL70.03992676365519930.8353357093775060.999311006273513
AZA vs. SAHA0.02086628047604490.931858021115620.984897965256188
DISU vs. CD3-0.514466648025460.1570323882738470.26515646344461
DISU vs. IL7-0.02421747799387560.9233361304434030.985909727897307
DISU vs. SAHA-0.03285386194196670.9102703674563730.979455391740835
DMSO vs. AZA0.05356899031644710.748882199184911
DMSO vs. CD3-0.5170353490174870.1066452700669530.180051231748564
DMSO vs. DISU-0.004080002458513170.9866424696646710.997977034037055
DMSO vs. IL7-0.006091647510445670.9729429342857930.995107375435449
DMSO vs. SAHA-0.03878336456920910.8693036086254720.966884129265183
HIV vs. Mock in Activation-0.01586403734198070.9796321844787530.999983755607037
HIV vs. Mock in Latency-0.1344273238024730.4146230033431210.999834320637052
IL7 vs. CD3-0.5092745141544490.1135521300407320.209187393803955
SAHA vs. CD3-0.5610654749957540.1127677355214050.191936952146778
SAHA vs. IL7-0.02281191003283410.925332043913570.972727391659224
(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 -0.459844 0.583808
(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
0.959 0.933 0.925 0.933 0.921
(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
not found