Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002991
UniProt IDQ86V81
Primary gene name(s)ALYREF
Synonym gene name(s)ALY, BEF, THOC4
Protein nameTHO complex subunit 4
Protein functionExport adapter involved in nuclear export of spliced and unspliced mRNA. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export, TAP/NFX1 pathway. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex, EJC and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm. TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus, KSHV intronless mRNAs and infectious virus production; ALYREF/THOC4 mediates the recruitment of the TREX complex to the intronless viral mRNA. Required for TREX complex assembly and for linking DDX39B to the cap-binding complex, CBC. In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim. Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B. Involved in transcription elongation and genome stability. {ECO:0000269|PubMed:25662211}.; FUNCTION: Acts as chaperone and promotes the dimerization of transcription factors containing basic leucine zipper, bZIP domains and thereby promotes transcriptional activation.
Subcellular locationNucleus {ECO:0000269|PubMed:10488337, ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:23826332, ECO:0000305|PubMed:18974867}. Nucleus speckle {ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:23826332}. Cytoplasm {ECO:0000269|PubMed:19324961}. Note=Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and DDX39B in the nucleus and nuclear speckles. Travels to the cytoplasm as part of the exon junction complex, EJC bound to mRNA, PubMed:19324961. Localizes to regions surrounding nuclear speckles known as perispeckles in which TREX complex assembly seems to occur, PubMed:23826332. {ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:23826332}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q86V81
Gene Ontology
(Biological Process)
Complete annatation
mRNA 3'-end processing [GO:0031124];
mRNA export from nucleus [GO:0006406];
mRNA splicing, via spliceosome [GO:0000398];
osteoblast differentiation [GO:0001649];
positive regulation of DNA-templated transcription, elongation [GO:0032786];
regulation of DNA recombination [GO:0000018];
replication fork processing [GO:0031297];
RNA export from nucleus [GO:0006405];
termination of RNA polymerase II transcription [GO:0006369];
viral mRNA export from host cell nucleus [GO:0046784]
Gene Ontology
(Molecular Function)
Complete annatation
nucleotide binding [GO:0000166];
poly(A RNA binding [GO:0044822]
Gene Ontology
(Cellular Component)
Complete annatation
catalytic step 2 spliceosome [GO:0071013];
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
intracellular membrane-bounded organelle [GO:0043231];
membrane [GO:0016020];
nuclear speck [GO:0016607];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
transcription export complex [GO:0000346]
Protein-protein interaction115486
Phylogenetic treeQ86V81
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. CD31.796074027641671.06526095389192e-071.01940400616248e-06
AZA vs. DISU-0.04809800647063650.8497921314270650.988692756671169
AZA vs. IL70.4371404305969840.02419742071995680.496904254103418
AZA vs. SAHA-0.6052591720129520.01405369204543190.121974567640849
DISU vs. CD3-1.856265300565357.35613081226383e-077.35808333537259e-06
DISU vs. IL70.476011495089370.06028779480502990.323891128540921
DISU vs. SAHA-0.5554821912564090.05831719944101540.304325282446035
DMSO vs. AZA-0.05479804178811410.7465530844314791
DMSO vs. CD3-1.86303298555031.72038754353565e-081.74882849820274e-07
DMSO vs. DISU-0.008800952579546270.9713477155341990.995077522347534
DMSO vs. IL70.4993832266724910.005933298949037160.158308817091567
DMSO vs. SAHA-0.5565081568676550.01938254680259730.138915463423581
HIV vs. Mock in Activation0.07023914526089770.9101229956880420.999983755607037
HIV vs. Mock in Latency-0.1192227093158050.4770865366312830.999834320637052
IL7 vs. CD3-1.351802519061773.52359690576343e-050.000234279559596701
SAHA vs. CD3-2.425774157674727.48622275281718e-111.65664283237819e-09
SAHA vs. IL7-1.044938106279752.38941043591012e-050.000626399528885377
(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
1.9 0.03973363 1.2 0.19074427 1.2 0.342771114
(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 0.451175 0.00132191
(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
1.011 1.033 0.907 0.78 0.97
(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
3ULH X-ray 2.5Å A=78-183.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 complexes with 23125841
Gag-Pol complexes with 23125841
Rev inhibits 24753416
Pr55(Gag) complexes with 23125841
Nef complexes with 23125841

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03013 RNA transport - Homo sapiens (human)
hsa03015 mRNA surveillance pathway - Homo sapiens (human)
hsa03040 Spliceosome - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)