O08583 · THOC4_MOUSE

  • Protein
    THO complex subunit 4
  • Gene
    Alyref
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

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:10786854, PubMed:11158589, PubMed:9119228).
Functions as an mRNA export adapter; component of the transcription/export (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 via the TAP/NXF1 pathway. Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B. Plays a key role in mRNP recognition and mRNA packaging by bridging the mRNP-bound EJC and the TREX core complex. 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). Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway). 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 mRNA export of C5-methylcytosine (m5C)-containing mRNAs: specifically recognizes and binds m5C mRNAs and mediates their nucleo-cytoplasmic shuttling. Acts as a chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation. Involved in transcription elongation and genome stability (By similarity).

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentnuclear speck
Cellular Componentnucleus
Cellular Componentspliceosomal complex
Molecular FunctionC5-methylcytidine-containing RNA reader activity
Molecular Functionmolecular adaptor activity
Molecular FunctionmRNA binding
Molecular FunctionRNA binding
Molecular FunctionRNA folding chaperone
Molecular Functionsingle-stranded DNA binding
Biological ProcessmRNA export from nucleus
Biological ProcessmRNA processing
Biological ProcessRNA export from nucleus
Biological ProcessRNA splicing

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    THO complex subunit 4
  • Short names
    Tho4
  • Alternative names
    • Ally of AML-1 and LEF-1
    • Aly/REF export factor
    • REF1-I
    • RNA and export factor-binding protein 1
    • Transcriptional coactivator Aly/REF

Gene names

    • Name
      Alyref
    • Synonyms
      Aly, Ref1, Refbp1, THOC4

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    O08583
  • Secondary accessions
    • Q0VBL5
    • Q8CBM4
    • Q9JJW7

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Nucleus speckle
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. Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA.

Keywords

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain.

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylalanine
ChainPRO_00000819752-255THO complex subunit 4
Modified residue8Phosphoserine
Modified residue38Asymmetric dimethylarginine; alternate
Modified residue38Omega-N-methylarginine; alternate
Modified residue58Omega-N-methylarginine
Modified residue63Omega-N-methylarginine
Modified residue70Omega-N-methylarginine
Modified residue85N6-acetyllysine
Modified residue93Phosphoserine
Modified residue140Citrulline
Modified residue196Asymmetric dimethylarginine; alternate
Modified residue196Omega-N-methylarginine; alternate
Modified residue203Asymmetric dimethylarginine; alternate
Modified residue203Dimethylated arginine; alternate
Modified residue203Omega-N-methylarginine; alternate
Modified residue218Omega-N-methylarginine
Modified residue233N6-methyllysine
Modified residue237Phosphoserine

Post-translational modification

Arg-50 and Arg-203 are dimethylated, probably to asymmetric dimethylarginine. Arginine methylation reduces RNA binding (By similarity).
Citrullinated by PADI4.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.

Gene expression databases

Interaction

Subunit

Homomultimer; predominantly hexamer when bound to EJC-RNA complex. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex (THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7); in the complex interacts (via UAP56-binding motif) with DDX39B with low affinity but this interaction is likely stabilized by multimerization. TREX seems to have a dynamic structure involving ATP-dependent remodeling; in the complex interacts with THOC1, THOC2 and THOC5. Component of the ALYREF/THOC4-EJC-RNA complex; in the complex interacts (via the WXHD motif) with EIF4A3 and interacts (via the RRM domain) with MAGOH; these interactions are likely specific to RNA-bound EJC. Bridges the THO-DDX39B and EJC-RNA complexes to form the TREX-EJC-RNA complex; this interaction is essential for mRNP recognition and mRNA packaging. Identified in the spliceosome C complex. Found in a mRNP complex with UPF3A and UPF3B. Interacts with RBM8A, RBM15B, NCBP1, LEF1, RUNX1, RNPS1, SRRM1, IWS1 and EXOSC1. Interacts with RBM15B. Interacts with NXF1; the interaction is direct (PubMed:10786854).
Interacts with IVNS1ABP (via BACK domain); the interaction is indirect and likely plays a role in mRNA nuclear export

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for compositional bias, region, motif, domain.

TypeIDPosition(s)Description
Compositional bias1-17Basic and acidic residues
Region1-83Disordered
Region5-13N-terminal UAP56-binding motif
Region13-103RNA-binding domain 1
Region16-37Sufficient for RNA-binding, interaction with NXF1-NXT1 heterodimer
Region55-181Required for interactions with EJC and multimerization
Motif86-89WXHD motif
Domain105-182RRM
Compositional bias185-200Polar residues
Region185-255Disordered
Region241-249C-terminal UAP56-binding motif

Sequence similarities

Belongs to the THOC4 family.

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

O08583-1

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.

  • Name
    1
  • Synonyms
    Refbp1-I
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    255
  • Mass (Da)
    26,940
  • Last updated
    2007-01-23 v3
  • Checksum
    F597235EBDD47C17
MADKMDMSLDDIIKLNRSQRGGRGGGRGRGRAGSQGGRGGAVQAAARVNRGGGPMRNRPAIARGAAGGGRNRPAPYSRPKQLPDKWQHDLFDSGFGGGAGVETGGKLLVSNLDFGVSDADIQELFAEFGTLKKAAVHYDRSGRSLGTADVHFERKADALKAMKQYNGVPLDGRPMNIQLVTSQIDTQRRPAQSINRGGMTRNRGSGGFGGGGTRRGTRGGSRGRGRGTGRNSKQQLSAEELDAQLDAYNARMDTS

O08583-2

  • Name
    2
  • Synonyms
    Refbp1-II
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Features

Showing features for compositional bias, alternative sequence.

TypeIDPosition(s)Description
Compositional bias1-17Basic and acidic residues
Alternative sequenceVSP_00859714-105in isoform 2
Compositional bias185-200Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U89876
EMBL· GenBank· DDBJ
AAC53117.1
EMBL· GenBank· DDBJ
mRNA
AJ252140
EMBL· GenBank· DDBJ
CAB76383.1
EMBL· GenBank· DDBJ
mRNA
AL663030
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH466558
EMBL· GenBank· DDBJ
EDL34770.1
EMBL· GenBank· DDBJ
Genomic DNA
BC120588
EMBL· GenBank· DDBJ
AAI20589.1
EMBL· GenBank· DDBJ
mRNA
BC137658
EMBL· GenBank· DDBJ
AAI37659.1
EMBL· GenBank· DDBJ
mRNA
AK035721
EMBL· GenBank· DDBJ
BAC29168.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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