O08583 · THOC4_MOUSE
- ProteinTHO complex subunit 4
- GeneAlyref
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids255 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | nuclear speck | |
Cellular Component | nucleus | |
Cellular Component | spliceosomal complex | |
Molecular Function | C5-methylcytidine-containing RNA reader activity | |
Molecular Function | molecular adaptor activity | |
Molecular Function | mRNA binding | |
Molecular Function | RNA binding | |
Molecular Function | RNA folding chaperone | |
Molecular Function | single-stranded DNA binding | |
Biological Process | mRNA export from nucleus | |
Biological Process | mRNA processing | |
Biological Process | RNA export from nucleus | |
Biological Process | RNA splicing |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTHO complex subunit 4
- Short namesTho4
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO08583
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000081975 | 2-255 | THO complex subunit 4 | |||
Sequence: ADKMDMSLDDIIKLNRSQRGGRGGGRGRGRAGSQGGRGGAVQAAARVNRGGGPMRNRPAIARGAAGGGRNRPAPYSRPKQLPDKWQHDLFDSGFGGGAGVETGGKLLVSNLDFGVSDADIQELFAEFGTLKKAAVHYDRSGRSLGTADVHFERKADALKAMKQYNGVPLDGRPMNIQLVTSQIDTQRRPAQSINRGGMTRNRGSGGFGGGGTRRGTRGGSRGRGRGTGRNSKQQLSAEELDAQLDAYNARMDTS | ||||||
Modified residue | 8 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 38 | Asymmetric dimethylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 38 | Omega-N-methylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 58 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 63 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 70 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 85 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 93 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 140 | Citrulline | ||||
Sequence: R | ||||||
Modified residue | 196 | Asymmetric dimethylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 196 | Omega-N-methylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 203 | Asymmetric dimethylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 203 | Dimethylated arginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 203 | Omega-N-methylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 218 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 233 | N6-methyllysine | ||||
Sequence: K | ||||||
Modified residue | 237 | Phosphoserine | ||||
Sequence: S |
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
- PTM
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
Interacts with IVNS1ABP (via BACK domain); the interaction is indirect and likely plays a role in mRNA nuclear export
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region, motif, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-17 | Basic and acidic residues | ||||
Sequence: MADKMDMSLDDIIKLNR | ||||||
Region | 1-83 | Disordered | ||||
Sequence: MADKMDMSLDDIIKLNRSQRGGRGGGRGRGRAGSQGGRGGAVQAAARVNRGGGPMRNRPAIARGAAGGGRNRPAPYSRPKQLP | ||||||
Region | 5-13 | N-terminal UAP56-binding motif | ||||
Sequence: MDMSLDDII | ||||||
Region | 13-103 | RNA-binding domain 1 | ||||
Sequence: IKLNRSQRGGRGGGRGRGRAGSQGGRGGAVQAAARVNRGGGPMRNRPAIARGAAGGGRNRPAPYSRPKQLPDKWQHDLFDSGFGGGAGVET | ||||||
Region | 16-37 | Sufficient for RNA-binding, interaction with NXF1-NXT1 heterodimer | ||||
Sequence: NRSQRGGRGGGRGRGRAGSQGG | ||||||
Region | 55-181 | Required for interactions with EJC and multimerization | ||||
Sequence: MRNRPAIARGAAGGGRNRPAPYSRPKQLPDKWQHDLFDSGFGGGAGVETGGKLLVSNLDFGVSDADIQELFAEFGTLKKAAVHYDRSGRSLGTADVHFERKADALKAMKQYNGVPLDGRPMNIQLVT | ||||||
Motif | 86-89 | WXHD motif | ||||
Sequence: WQHD | ||||||
Domain | 105-182 | RRM | ||||
Sequence: GKLLVSNLDFGVSDADIQELFAEFGTLKKAAVHYDRSGRSLGTADVHFERKADALKAMKQYNGVPLDGRPMNIQLVTS | ||||||
Compositional bias | 185-200 | Polar residues | ||||
Sequence: DTQRRPAQSINRGGMT | ||||||
Region | 185-255 | Disordered | ||||
Sequence: DTQRRPAQSINRGGMTRNRGSGGFGGGGTRRGTRGGSRGRGRGTGRNSKQQLSAEELDAQLDAYNARMDTS | ||||||
Region | 241-249 | C-terminal UAP56-binding motif | ||||
Sequence: LDAQLDAYN |
Sequence similarities
Belongs to the THOC4 family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
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.
- Name1
- SynonymsRefbp1-I
- Length255
- Mass (Da)26,940
- Last updated2007-01-23 v3
- ChecksumF597235EBDD47C17
O08583-2
- Name2
- SynonymsRefbp1-II
- Differences from canonical
- 14-105: Missing
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-17 | Basic and acidic residues | ||||
Sequence: MADKMDMSLDDIIKLNR | ||||||
Alternative sequence | VSP_008597 | 14-105 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 185-200 | Polar residues | ||||
Sequence: DTQRRPAQSINRGGMT |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |