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Protein

THO complex subunit 4

Gene

Alyref

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.
Acts as chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation.

GO - Molecular functioni

  • nucleotide binding Source: InterPro
  • RNA binding Source: MGI
  • single-stranded DNA binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Biological processi

mRNA processing, mRNA splicing, mRNA transport, Transport

Keywords - Ligandi

RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
THO complex subunit 4
Short name:
Tho4
Alternative name(s):
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 namesi
Name:Alyref
Synonyms:Aly, Ref1, Refbp1, THOC4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1341044. Alyref.

Subcellular locationi

  • Nucleus 1 Publication
  • Nucleus speckle By similarity
  • Cytoplasm 1 Publication

  • 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.By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nuclear speck Source: UniProtKB-SubCell
  • nucleus Source: MGI
  • spliceosomal complex Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus, Spliceosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000819752 – 255THO complex subunit 4Add BLAST254

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei8PhosphoserineBy similarity1
Modified residuei38Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei38Omega-N-methylarginine; alternateCombined sources1
Modified residuei50Omega-N-methylated arginineBy similarity1
Modified residuei58Omega-N-methylarginineBy similarity1
Modified residuei63Omega-N-methylarginineBy similarity1
Modified residuei70Omega-N-methylarginineBy similarity1
Modified residuei85N6-acetyllysineCombined sources1
Modified residuei93PhosphoserineBy similarity1
Modified residuei140Citrulline1 Publication1
Modified residuei196Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei196Omega-N-methylarginine; alternateCombined sources1
Modified residuei203Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei203Dimethylated arginine; alternateBy similarity1
Modified residuei203Omega-N-methylarginine; alternateCombined sources1
Modified residuei203Omega-N-methylated arginine; alternateBy similarity1
Modified residuei218Omega-N-methylarginineBy similarity1
Modified residuei233N6-methyllysineBy similarity1
Modified residuei237PhosphoserineBy similarity1

Post-translational modificationi

Arg-50 and Arg-203 are dimethylated, probably to asymmetric dimethylarginine. Arginine methylation reduces RNA binding (By similarity).By similarity
Citrullinated by PADI4.1 Publication

Keywords - PTMi

Acetylation, Citrullination, Methylation, Phosphoprotein

Proteomic databases

EPDiO08583.
MaxQBiO08583.
PaxDbiO08583.
PeptideAtlasiO08583.
PRIDEiO08583.
TopDownProteomicsiO08583-1. [O08583-1]

PTM databases

iPTMnetiO08583.
PhosphoSitePlusiO08583.

Expressioni

Tissue specificityi

Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000025134.
CleanExiMM_THOC4.
GenevisibleiO08583. MM.

Interactioni

Subunit structurei

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.1 Publication

Protein-protein interaction databases

BioGridi204102. 4 interactors.
DIPiDIP-59977N.
IntActiO08583. 3 interactors.
MINTiMINT-1867899.
STRINGi10090.ENSMUSP00000026125.

Structurei

Secondary structure

1255
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi106 – 111Combined sources6
Helixi118 – 128Combined sources11
Beta strandi131 – 137Combined sources7
Beta strandi147 – 153Combined sources7
Helixi155 – 165Combined sources11
Beta strandi176 – 180Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NO8NMR-A77-182[»]
ProteinModelPortaliO08583.
SMRiO08583.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO08583.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini105 – 182RRMPROSITE-ProRule annotationAdd BLAST78

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni16 – 37Sufficient for RNA-binding, interaction with NXF1-NXT1 heterodimerBy similarityAdd BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi21 – 229Ala/Arg/Gly-richAdd BLAST209

Sequence similaritiesi

Belongs to the THOC4 family.Curated
Contains 1 RRM (RNA recognition motif) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0533. Eukaryota.
ENOG4111JAW. LUCA.
GeneTreeiENSGT00410000025615.
HOGENOMiHOG000239962.
HOVERGENiHBG054806.
InParanoidiO08583.
KOiK12881.
OMAiEKWQHDL.
OrthoDBiEOG091G0T4Z.
PhylomeDBiO08583.
TreeFamiTF313312.

Family and domain databases

Gene3Di3.30.70.330. 1 hit.
InterProiIPR025715. FoP_C.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF13865. FoP_duplication. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM01218. FoP_duplication. 1 hit.
SM00360. RRM. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O08583-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MADKMDMSLD DIIKLNRSQR GGRGGGRGRG RAGSQGGRGG AVQAAARVNR
60 70 80 90 100
GGGPMRNRPA IARGAAGGGR NRPAPYSRPK QLPDKWQHDL FDSGFGGGAG
110 120 130 140 150
VETGGKLLVS NLDFGVSDAD IQELFAEFGT LKKAAVHYDR SGRSLGTADV
160 170 180 190 200
HFERKADALK AMKQYNGVPL DGRPMNIQLV TSQIDTQRRP AQSINRGGMT
210 220 230 240 250
RNRGSGGFGG GGTRRGTRGG SRGRGRGTGR NSKQQLSAEE LDAQLDAYNA

RMDTS
Length:255
Mass (Da):26,940
Last modified:January 23, 2007 - v3
Checksum:iF597235EBDD47C17
GO
Isoform 2 (identifier: O08583-2) [UniParc]FASTAAdd to basket
Also known as: Refbp1-II

The sequence of this isoform differs from the canonical sequence as follows:
     14-105: Missing.

Show »
Length:163
Mass (Da):17,682
Checksum:iD212F3ACD29C8B13
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00859714 – 105Missing in isoform 2. 1 PublicationAdd BLAST92

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS25744.1. [O08583-1]
RefSeqiNP_035698.1. NM_011568.1. [O08583-1]
UniGeneiMm.1886.

Genome annotation databases

EnsembliENSMUST00000026125; ENSMUSP00000026125; ENSMUSG00000025134. [O08583-1]
GeneIDi21681.
KEGGimmu:21681.
UCSCiuc007mtl.1. mouse. [O08583-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS25744.1. [O08583-1]
RefSeqiNP_035698.1. NM_011568.1. [O08583-1]
UniGeneiMm.1886.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NO8NMR-A77-182[»]
ProteinModelPortaliO08583.
SMRiO08583.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204102. 4 interactors.
DIPiDIP-59977N.
IntActiO08583. 3 interactors.
MINTiMINT-1867899.
STRINGi10090.ENSMUSP00000026125.

PTM databases

iPTMnetiO08583.
PhosphoSitePlusiO08583.

Proteomic databases

EPDiO08583.
MaxQBiO08583.
PaxDbiO08583.
PeptideAtlasiO08583.
PRIDEiO08583.
TopDownProteomicsiO08583-1. [O08583-1]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026125; ENSMUSP00000026125; ENSMUSG00000025134. [O08583-1]
GeneIDi21681.
KEGGimmu:21681.
UCSCiuc007mtl.1. mouse. [O08583-1]

Organism-specific databases

CTDi10189.
MGIiMGI:1341044. Alyref.

Phylogenomic databases

eggNOGiKOG0533. Eukaryota.
ENOG4111JAW. LUCA.
GeneTreeiENSGT00410000025615.
HOGENOMiHOG000239962.
HOVERGENiHBG054806.
InParanoidiO08583.
KOiK12881.
OMAiEKWQHDL.
OrthoDBiEOG091G0T4Z.
PhylomeDBiO08583.
TreeFamiTF313312.

Miscellaneous databases

EvolutionaryTraceiO08583.
PROiO08583.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025134.
CleanExiMM_THOC4.
GenevisibleiO08583. MM.

Family and domain databases

Gene3Di3.30.70.330. 1 hit.
InterProiIPR025715. FoP_C.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF13865. FoP_duplication. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM01218. FoP_duplication. 1 hit.
SM00360. RRM. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTHOC4_MOUSE
AccessioniPrimary (citable) accession number: O08583
Secondary accession number(s): Q0VBL5, Q8CBM4, Q9JJW7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 145 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.