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Protein

THO complex subunit 4

Gene

ALYREF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

Miscellaneous

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChaperone, RNA-binding
Biological processHost-virus interaction, mRNA processing, mRNA splicing, mRNA transport, Transport

Enzyme and pathway databases

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
MIMi604171 gene
neXtProtiNX_Q86V81

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi69973
TopDownProteomicsiQ86V81

PTM databases

iPTMnetiQ86V81
PhosphoSitePlusiQ86V81

Miscellaneous databases

PMAP-CutDBiQ86V81

Expressioni

Tissue specificityi

Expressed in a wide variety of cancer types.1 Publication

Gene expression databases

CleanExiHS_THOC4

Organism-specific databases

HPAiHPA019799
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 RBM15B (PubMed:19586903). Interacts with NXF1; the interaction is direct.21 Publications
(Microbial infection) 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.2 Publications
(Microbial infection) Interacts with HHV-1 ICP27 protein; this interaction recruits ALYREF to viral replication compartments and probably directs viral mRNA to the TAP/NFX1 pathway.2 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi115486, 149 interactors
CORUMiQ86V81
DIPiDIP-32711N
IntActiQ86V81, 62 interactors
MINTiQ86V81
STRINGi9606.ENSP00000421592

Structurei

Secondary structure

1257
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

eggNOGiKOG0533 Eukaryota
ENOG4111JAW LUCA
HOGENOMiHOG000239962
HOVERGENiHBG054806
InParanoidiQ86V81
KOiK12881
PhylomeDBiQ86V81

Family and domain databases

Gene3Di3.30.70.330, 1 hit
InterProiView protein in InterPro
IPR025715 FoP_C
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
PfamiView protein in Pfam
PF13865 FoP_duplication, 1 hit
PF00076 RRM_1, 1 hit
SMARTiView protein in SMART
SM01218 FoP_duplication, 1 hit
SM00360 RRM, 1 hit
SUPFAMiSSF54928 SSF54928, 1 hit
PROSITEiView protein in PROSITE
PS50102 RRM, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PB61E9PB61_HUMAN
THO complex subunit 4
ALYREF
264Annotation score:

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

Similar proteinsi

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, 149 interactors
CORUMiQ86V81
DIPiDIP-32711N
IntActiQ86V81, 62 interactors
MINTiQ86V81
STRINGi9606.ENSP00000421592

PTM databases

iPTMnetiQ86V81
PhosphoSitePlusiQ86V81

Polymorphism and mutation databases

BioMutaiALYREF
DMDMi48429165

Proteomic databases

EPDiQ86V81
MaxQBiQ86V81
PaxDbiQ86V81
PeptideAtlasiQ86V81
PRIDEiQ86V81
ProteomicsDBi69973
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
HPAiHPA019799
HPA061282
MIMi604171 gene
neXtProtiNX_Q86V81
PharmGKBiPA134925107
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0533 Eukaryota
ENOG4111JAW LUCA
HOGENOMiHOG000239962
HOVERGENiHBG054806
InParanoidiQ86V81
KOiK12881
PhylomeDBiQ86V81

Enzyme and pathway databases

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-CutDBiQ86V81
PROiPR:Q86V81
SOURCEiSearch...

Gene expression databases

CleanExiHS_THOC4

Family and domain databases

Gene3Di3.30.70.330, 1 hit
InterProiView protein in InterPro
IPR025715 FoP_C
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
PfamiView protein in Pfam
PF13865 FoP_duplication, 1 hit
PF00076 RRM_1, 1 hit
SMARTiView protein in SMART
SM01218 FoP_duplication, 1 hit
SM00360 RRM, 1 hit
SUPFAMiSSF54928 SSF54928, 1 hit
PROSITEiView protein in PROSITE
PS50102 RRM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTHOC4_HUMAN
AccessioniPrimary (citable) accession number: Q86V81
Secondary accession number(s): O43672
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 167 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

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

Documents

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