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Protein

THO complex subunit 4

Gene

ALYREF

Organism
Homo sapiens (Human)
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. 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. 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.1 Publication
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
  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

  • mRNA 3'-end processing Source: Reactome
  • mRNA export from nucleus Source: UniProtKB
  • mRNA splicing, via spliceosome Source: UniProtKB
  • osteoblast differentiation Source: UniProtKB
  • positive regulation of DNA-templated transcription, elongation Source: UniProtKB
  • regulation of DNA recombination Source: UniProtKB
  • replication fork processing Source: UniProtKB
  • RNA export from nucleus Source: Reactome
  • termination of RNA polymerase II transcription Source: Reactome
  • viral mRNA export from host cell nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Biological processi

Host-virus interaction, mRNA processing, mRNA splicing, mRNA transport, Transport

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:G66-30958-MONOMER.
ReactomeiR-HSA-109688. Cleavage of Growing Transcript in the Termination Region.
R-HSA-159227. Transport of the SLBP independent Mature mRNA.
R-HSA-159230. Transport of the SLBP Dependant Mature mRNA.
R-HSA-159231. Transport of Mature mRNA Derived from an Intronless Transcript.
R-HSA-159236. Transport of Mature mRNA derived from an Intron-Containing Transcript.
R-HSA-72163. mRNA Splicing - Major Pathway.
R-HSA-72187. mRNA 3'-end processing.
SIGNORiQ86V81.

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
Transcriptional coactivator Aly/REF
bZIP-enhancing factor BEF
Gene namesi
Name:ALYREF
Synonyms:ALY, BEF, THOC4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:19071. ALYREF.

Subcellular locationi

GO - Cellular componenti

  • catalytic step 2 spliceosome Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • membrane Source: UniProtKB
  • nuclear speck Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: HPA
  • transcription export complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus, Spliceosome

Pathology & Biotechi

Organism-specific databases

DisGeNETi10189.
PharmGKBiPA134925107.

Polymorphism and mutation databases

BioMutaiALYREF.
DMDMi48429165.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00000819742 – 257THO complex subunit 4Add BLAST256

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources2 Publications1
Modified residuei8PhosphoserineCombined sources1
Modified residuei38Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei38Omega-N-methylarginine; alternateCombined sources1
Modified residuei58Omega-N-methylarginineCombined sources1
Modified residuei63Omega-N-methylarginineCombined sources1
Modified residuei71Omega-N-methylarginineCombined sources1
Modified residuei86N6-acetyllysineBy similarity1
Modified residuei94PhosphoserineCombined sources1
Modified residuei141CitrullineBy similarity1
Modified residuei197Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei197Omega-N-methylarginine; alternateBy similarity1
Modified residuei204Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei204Dimethylated arginine; alternateCombined sources1 Publication1
Modified residuei204Omega-N-methylarginine; alternateBy similarity1
Modified residuei204Omega-N-methylated arginine; alternate1 Publication1
Modified residuei220Omega-N-methylarginine1 Publication1
Modified residuei235N6-methyllysineCombined sources1
Modified residuei239PhosphoserineCombined sources1

Post-translational modificationi

Arg-204 is dimethylated, probably to asymmetric dimethylarginine. Arginine methylation reduces RNA binding.2 Publications
Citrullinated by PADI4.By similarity

Keywords - PTMi

Acetylation, Citrullination, Methylation, Phosphoprotein

Proteomic databases

EPDiQ86V81.
MaxQBiQ86V81.
PaxDbiQ86V81.
PeptideAtlasiQ86V81.
PRIDEiQ86V81.
TopDownProteomicsiQ86V81.

PTM databases

iPTMnetiQ86V81.
PhosphoSitePlusiQ86V81.

Miscellaneous databases

PMAP-CutDBQ86V81.

Expressioni

Tissue specificityi

Expressed in a wide variety of cancer types.1 Publication

Gene expression databases

BgeeiENSG00000183684.
CleanExiHS_THOC4.

Organism-specific databases

HPAiCAB016281.
HPA019799.
HPA061282.

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. Interacts with human Kaposi's sarcoma-associated herpesvirus (HHV-8) ORF57 protein; this interaction allows efficient export of HHV-8 early and late intronless transcripts. Interacts with HHV-1 ICP27 protein; this interaction recruits ALYREF to viral replication compartments and probably directs viral mRNA to the TAP/NFX1 pathway.22 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CHTOPQ9Y3Y28EBI-347640,EBI-347794
DDX39BQ138384EBI-347640,EBI-348622
NXF1Q9UBU94EBI-347640,EBI-398874

Protein-protein interaction databases

BioGridi115486. 122 interactors.
DIPiDIP-32711N.
IntActiQ86V81. 49 interactors.
MINTiMINT-5001811.
STRINGi9606.ENSP00000421592.

Structurei

Secondary structure

1257
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi105 – 112Combined sources8
Helixi119 – 127Combined sources9
Beta strandi132 – 139Combined sources8
Beta strandi145 – 155Combined sources11
Helixi156 – 166Combined sources11
Beta strandi177 – 181Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3ULHX-ray2.54A78-183[»]
ProteinModelPortaliQ86V81.
SMRiQ86V81.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini106 – 183RRMPROSITE-ProRule annotationAdd BLAST78

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni16 – 37Sufficient for RNA-binding, interaction with NXF1-NXT1 heterodimerAdd BLAST22
Regioni85 – 186Interaction with HHV-8 ORF57 protein and with ICP27 from HHV-1By similarityAdd BLAST102

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi21 – 231Ala/Arg/Gly-richAdd BLAST211

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0533. Eukaryota.
ENOG4111JAW. LUCA.
HOGENOMiHOG000239962.
HOVERGENiHBG054806.
InParanoidiQ86V81.
KOiK12881.
PhylomeDBiQ86V81.

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]

Sequencei

Sequence statusi: Complete.

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

Q86V81-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADKMDMSLD DIIKLNRSQR GGRGGGRGRG RAGSQGGRGG GAQAAARVNR
60 70 80 90 100
GGGPIRNRPA IARGAAGGGG RNRPAPYSRP KQLPDKWQHD LFDSGFGGGA
110 120 130 140 150
GVETGGKLLV SNLDFGVSDA DIQELFAEFG TLKKAAVHYD RSGRSLGTAD
160 170 180 190 200
VHFERKADAL KAMKQYNGVP LDGRPMNIQL VTSQIDAQRR PAQSVNRGGM
210 220 230 240 250
TRNRGAGGFG GGGGTRRGTR GGARGRGRGA GRNSKQQLSA EELDAQLDAY

NARMDTS
Length:257
Mass (Da):26,888
Last modified:January 23, 2007 - v3
Checksum:iE2B5021DA579919A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26G → R in AAD09608 (PubMed:9952027).Curated1
Sequence conflicti35 – 36QG → RA in AAD09608 (PubMed:9952027).Curated2
Sequence conflicti39G → R in AAD09608 (PubMed:9952027).Curated1
Sequence conflicti150D → N in AAD09608 (PubMed:9952027).Curated1
Sequence conflicti169V → F in AAD09608 (PubMed:9952027).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC145207 Genomic DNA. No translation available.
BC052302 mRNA. Translation: AAH52302.1.
AF047002 mRNA. Translation: AAD09608.1.
RefSeqiNP_005773.3. NM_005782.3.
UniGeneiHs.534385.

Genome annotation databases

EnsembliENST00000331204; ENSP00000331817; ENSG00000183684.
GeneIDi10189.
KEGGihsa:10189.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC145207 Genomic DNA. No translation available.
BC052302 mRNA. Translation: AAH52302.1.
AF047002 mRNA. Translation: AAD09608.1.
RefSeqiNP_005773.3. NM_005782.3.
UniGeneiHs.534385.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3ULHX-ray2.54A78-183[»]
ProteinModelPortaliQ86V81.
SMRiQ86V81.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115486. 122 interactors.
DIPiDIP-32711N.
IntActiQ86V81. 49 interactors.
MINTiMINT-5001811.
STRINGi9606.ENSP00000421592.

PTM databases

iPTMnetiQ86V81.
PhosphoSitePlusiQ86V81.

Polymorphism and mutation databases

BioMutaiALYREF.
DMDMi48429165.

Proteomic databases

EPDiQ86V81.
MaxQBiQ86V81.
PaxDbiQ86V81.
PeptideAtlasiQ86V81.
PRIDEiQ86V81.
TopDownProteomicsiQ86V81.

Protocols and materials databases

DNASUi10189.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000331204; ENSP00000331817; ENSG00000183684.
GeneIDi10189.
KEGGihsa:10189.

Organism-specific databases

CTDi10189.
DisGeNETi10189.
GeneCardsiALYREF.
HGNCiHGNC:19071. ALYREF.
HPAiCAB016281.
HPA019799.
HPA061282.
MIMi604171. gene.
neXtProtiNX_Q86V81.
PharmGKBiPA134925107.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0533. Eukaryota.
ENOG4111JAW. LUCA.
HOGENOMiHOG000239962.
HOVERGENiHBG054806.
InParanoidiQ86V81.
KOiK12881.
PhylomeDBiQ86V81.

Enzyme and pathway databases

BioCyciZFISH:G66-30958-MONOMER.
ReactomeiR-HSA-109688. Cleavage of Growing Transcript in the Termination Region.
R-HSA-159227. Transport of the SLBP independent Mature mRNA.
R-HSA-159230. Transport of the SLBP Dependant Mature mRNA.
R-HSA-159231. Transport of Mature mRNA Derived from an Intronless Transcript.
R-HSA-159236. Transport of Mature mRNA derived from an Intron-Containing Transcript.
R-HSA-72163. mRNA Splicing - Major Pathway.
R-HSA-72187. mRNA 3'-end processing.
SIGNORiQ86V81.

Miscellaneous databases

ChiTaRSiALYREF. human.
GeneWikiiTHOC4.
GenomeRNAii10189.
PMAP-CutDBQ86V81.
PROiQ86V81.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183684.
CleanExiHS_THOC4.

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_HUMAN
AccessioniPrimary (citable) accession number: Q86V81
Secondary accession number(s): O43672
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 152 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Antibodies against ALYREF/THOC4 are found in sera of patients with systemic lupus erythematosus (SLE).

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.