O08583 (THOC4_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 119. History...
Names and origin
|Protein names||Recommended name:|
THO complex subunit 4
Ally of AML-1 and LEF-1
Aly/REF export factor
RNA and export factor-binding protein 1
Transcriptional coactivator Aly/REF
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||255 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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). 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. 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. Ref.1 Ref.2 Ref.7
Homomultimer. Is part of several complexes involved in mRNA processing and export. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; TREX seems to have a dynamic structure involving ATP-dependent remodeling; in the complex interacts (via C-terminus) directly with DDX39B and interacts directly with THOC1 and THOC2. Found in mRNA splicing-dependent exon junction complexes (EJC). Identified in the spliceosome C complex. Found in a mRNP complex with UPF3A and UPF3B. Interacts with RBM8A, NCBP1, THOC5, LEF1, RUNX1, EIF4A3, RNPS1, SRRM1, IWS1 and EXOSC1. Interacts with NXF1; the interaction is direct. Ref.2
Nucleus. Nucleus speckle By similarity. Cytoplasm. Note: Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and DDX39B in the nucleus and nuclear speckles. Localizes to regions surrounding nuclear speckles known as perispeckles in which TREX complex assembly seems to occur By similarity. Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA. Ref.1
Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Ref.1
Arg-50 and Arg-203 are dimethylated, probably to asymmetric dimethylarginine. Arginine methylation reduces RNA binding By similarity.
Belongs to the THOC4 family.
Contains 1 RRM (RNA recognition motif) domain.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: O08583-1) |
Also known as: Refbp1-I;
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform 2 (identifier: O08583-2) |
Also known as: Refbp1-II;
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 255||254||THO complex subunit 4||PRO_0000081975|
|Domain||105 – 182||78||RRM|
|Region||16 – 37||22||Sufficient for RNA-binding, interaction with NXF1-NXT1 heterodimer By similarity|
|Compositional bias||21 – 229||209||Ala/Arg/Gly-rich|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine By similarity|
|Modified residue||8||1||Phosphoserine By similarity|
|Modified residue||50||1||Omega-N-methylated arginine By similarity|
|Modified residue||93||1||Phosphoserine By similarity|
|Modified residue||203||1||Dimethylated arginine; alternate By similarity|
|Modified residue||203||1||Omega-N-methylated arginine; alternate By similarity|
|Modified residue||237||1||Phosphoserine By similarity|
|Alternative sequence||14 – 105||92||Missing in isoform 2.||VSP_008597|
Helix Strand Turn
|Beta strand||106 – 111||6|
|Helix||118 – 128||11|
|Beta strand||131 – 137||7|
|Beta strand||147 – 153||7|
|Helix||155 – 165||11|
|Beta strand||176 – 180||5|
|||"ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function."|
Bruhn L., Munnerlyn A., Grosschedl R.
Genes Dev. 11:640-653(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
|||"REF, an evolutionarily conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export."|
Stutz F., Bachi A., Doerks T., Braun I.C., Seraphin B., Wilm M., Bork P., Izaurralde E.
RNA 6:638-650(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH NXF1.
|||"Lineage-specific biology revealed by a finished genome assembly of the mouse."|
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|||Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.|
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||"The transcriptional landscape of the mammalian genome."|
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 190-255.
Tissue: Urinary bladder.
|||"REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus."|
Rodrigues J.P., Rode M., Gatfield D., Blencowe B.J., Carmo-Fonseca M., Izaurralde E.
Proc. Natl. Acad. Sci. U.S.A. 98:1030-1035(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Structure of the nuclear factor ALY: insights into post-transcriptional regulatory and mRNA nuclear export processes."|
Perez-Alvarado G.C., Martinez-Yamout M., Allen M.M., Grosschedl R., Dyson H.J., Wright P.E.
Biochemistry 42:7348-7357(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 105-182.
|+||Additional computationally mapped references.|
|U89876 mRNA. Translation: AAC53117.1.|
AJ252140 mRNA. Translation: CAB76383.1.
AL663030 Genomic DNA. Translation: CAM27086.1.
CH466558 Genomic DNA. Translation: EDL34770.1.
BC120588 mRNA. Translation: AAI20589.1.
BC137658 mRNA. Translation: AAI37659.1.
AK035721 mRNA. Translation: BAC29168.1.
|RefSeq||NP_035698.1. NM_011568.1. |
3D structure databases
|SMR||O08583. Positions 1-187. |
Protein-protein interaction databases
|BioGrid||204102. 3 interactions.|
|IntAct||O08583. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000026125; ENSMUSP00000026125; ENSMUSG00000025134. |
|UCSC||uc007mtl.1. mouse. |
|MGI||MGI:1341044. Alyref. |
Gene expression databases
Family and domain databases
|Gene3D||188.8.131.520. 1 hit. |
|InterPro||IPR025715. FoP_duplication. |
|Pfam||PF13865. FoP_duplication. 1 hit. |
PF00076. RRM_1. 1 hit.
|SMART||SM00360. RRM. 1 hit. |
|PROSITE||PS50102. RRM. 1 hit. |
|Accession||Primary (citable) accession number: O08583|
Secondary accession number(s): Q0VBL5, Q8CBM4, Q9JJW7
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|