THO complex subunit 4 (ALYREF)

The protein contains 257 amino acids for an estimated molecular weight of 26888 Da.

 

Export 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) (PubMed:15833825, PubMed:15998806, PubMed:17190602, PubMed:11707413, PubMed:11675789, PubMed:11979277, PubMed:18364396, PubMed:22144908, PubMed:22893130, PubMed:23222130, PubMed:25662211). 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 (PubMed:15833825, PubMed:15998806, PubMed:17190602). 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 (PubMed:15833825, PubMed:15998806, PubMed:17190602). TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1 (PubMed:15833825, PubMed:15998806, PubMed:17190602). 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 (PubMed:18974867). Required for TREX complex assembly and for linking DDX39B to the cap-binding complex (CBC) (PubMed:15998806, PubMed:17984224). In conjunction with THOC5 fu (updated: Oct. 16, 2019)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 0%
Model score: 41

(right-click above to access to more options from the contextual menu)

The reference OMIM entry for this protein is 604171

Tho complex, subunit 4; thoc4
Transcriptional coactivator aly; aly
Bzip-enhancing factor; bef

DESCRIPTION

In yeast, the TREX (transcription/export) complex contains the THO transcription elongation complex, which functions in cotranscriptional recruitment of mRNA export proteins to the nascent transcript. The human TREX complex contains THOC4, UAP56 (DDX39B; 142560), and the human counterpart of the THO complex (see THOC1; 606930). The human TREX complex appears to be recruited to spliced mRNAs late in the splicing reaction rather than by direct cotranscriptional recruitment, as in yeast (Masuda et al., 2005).

CLONING

Using a yeast 2-hybrid screen, Bruhn et al. (1997) isolated a novel murine gene that they designated ALY. Virbasius et al. (1999) identified and cloned a human nuclear protein that dramatically increases DNA binding of transcription factors containing a basic leucine zipper (bZIP) DNA-binding domain. They showed that this protein, which they called bZIP-enhancing factor (BEF), is identical to the murine ALY protein and functions as a molecular chaperone.

GENE FUNCTION

Bruhn et al. (1997) demonstrated that ALY is a ubiquitously expressed nuclear protein that specifically associates with the activation domains of LEF1 (153245) and AML1 (CBFA2; 151385). In addition, ALY can increase DNA binding by both LEF1 and AML proteins. Overexpression of ALY stimulated the activity of the TCR-alpha (see 186880) enhancer complex reconstituted in transfected nonlymphoid HeLa cells, whereas downregulation of ALY by antisense oligonucleotides virtually eliminated TCR-alpha enhancer activity in T cells. Similar to LEF1, ALY can stimulate transcription in the context of the TCR-alpha enhancer but apparently not when tethered to DNA through a heterologous DNA-binding domain. Bruhn et al. (1997) proposed that ALY mediates context-dependent transcriptional activation by facilitating the functional collaboration of multiple proteins in the TCR-alpha enhancer complex. Virbasius et al. (1999) demonstrated that BEF stimulates DNA binding by recognizing the unfolded leucine zipper and promoting the folding of bZIP monomers to dimers; the elevated concentration of the bZIP dimer then drives the DNA binding reaction. Antisense experiments indicated that BEF is required for efficient transcriptional activation by bZIP proteins in vivo. These results revealed protein folding in the nucleus as a step at which sequence-specific DNA-binding proteins can be regulated. Splicing of pre-mRNA and export of mRNA are normally coupled in vivo. During splicing, the conserved mRNA export factor ALY is recruited to the spliced mRNA-protein complex (mRNP), which targets the mRNA for export. Luo et al. (2001) showed that the conserved DEAD box helicase UAP56, which functions during spliceosome assembly, interacts directly and highly specifically with ALY. Moreover, UAP56 is present together with ALY in a spliced mRNP. Excess UAP56 is a potent dominant-negative inhibitor of mRNA export and inhibits the recruitment of ALY to the spliced mRNP. Furthermore, mutation in ALY that blocks its interaction with UAP56 prevents recruitment of ALY to the spliced mRNP. Luo et al. (2001) concluded that the splicing factor UAP56 functions in coupling the splicing and export machineries by recruiting ALY to the spliced mRNP. Strasser et al. (2002) showed that ALY is part of the RNase-resistant TREX complex, which includes TEX1 (606929), HPR1 (THOC1), THO2 (THOC2; 300395), and UAP56 and is conserved from yeast to humans. Functional studies in yeast ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 604171 was added.

Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Dec. 10, 2018: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).