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O08583 (THOC4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Alyref
Synonyms:Aly, Ref1, Refbp1, THOC4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length255 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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). 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. Ref.1 Ref.2 Ref.7

Acts as chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation. Ref.1 Ref.2 Ref.7

Subunit structure

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. Ref.2

Subcellular location

Nucleus. Nucleus speckle By similarity. 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 By similarity. Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA. Ref.1

Tissue specificity

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

Post-translational modification

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

Citrullinated by PADI4.

Sequence similarities

Belongs to the THOC4 family.

Contains 1 RRM (RNA recognition motif) domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O08583-1)

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.
Isoform 2 (identifier: O08583-2)

Also known as: Refbp1-II;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 255254THO complex subunit 4
PRO_0000081975

Regions

Domain105 – 18278RRM
Region16 – 3722Sufficient for RNA-binding, interaction with NXF1-NXT1 heterodimer By similarity
Compositional bias21 – 229209Ala/Arg/Gly-rich

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue81Phosphoserine By similarity
Modified residue501Omega-N-methylated arginine By similarity
Modified residue851N6-acetyllysine Ref.9
Modified residue931Phosphoserine By similarity
Modified residue1401Citrulline
Modified residue2031Dimethylated arginine; alternate By similarity
Modified residue2031Omega-N-methylated arginine; alternate By similarity
Modified residue2181Omega-N-methylarginine
Modified residue2371Phosphoserine By similarity

Natural variations

Alternative sequence14 – 10592Missing in isoform 2.
VSP_008597

Secondary structure

............. 255
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Refbp1-I) [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: F597235EBDD47C17

FASTA25526,940
        10         20         30         40         50         60 
MADKMDMSLD DIIKLNRSQR GGRGGGRGRG RAGSQGGRGG AVQAAARVNR GGGPMRNRPA 

        70         80         90        100        110        120 
IARGAAGGGR NRPAPYSRPK QLPDKWQHDL FDSGFGGGAG VETGGKLLVS NLDFGVSDAD 

       130        140        150        160        170        180 
IQELFAEFGT LKKAAVHYDR SGRSLGTADV HFERKADALK AMKQYNGVPL DGRPMNIQLV 

       190        200        210        220        230        240 
TSQIDTQRRP AQSINRGGMT RNRGSGGFGG GGTRRGTRGG SRGRGRGTGR NSKQQLSAEE 

       250 
LDAQLDAYNA RMDTS 

« Hide

Isoform 2 (Refbp1-II) [UniParc].

Checksum: D212F3ACD29C8B13
Show »

FASTA16317,682

References

« Hide 'large scale' references
[1]"ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function."
Bruhn L., Munnerlyn A., Grosschedl R.
Genes Dev. 11:640-653(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Thymocyte.
[2]"REF, an evolutionarily conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export."
Stutz F., Bachi A., Doerks T., Braun I.C., Seraphin B., Wilm M., Bork P., Izaurralde E.
RNA 6:638-650(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH NXF1.
Tissue: Embryo.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[6]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 190-255.
Strain: C57BL/6J.
Tissue: Urinary bladder.
[7]"REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus."
Rodrigues J.P., Rode M., Gatfield D., Blencowe B.J., Carmo-Fonseca M., Izaurralde E.
Proc. Natl. Acad. Sci. U.S.A. 98:1030-1035(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Citrullination regulates pluripotency and histone H1 binding to chromatin."
Christophorou M.A., Castelo-Branco G., Halley-Stott R.P., Oliveira C.S., Loos R., Radzisheuskaya A., Mowen K.A., Bertone P., Silva J.C., Zernicka-Goetz M., Nielsen M.L., Gurdon J.B., Kouzarides T.
Nature 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: CITRULLINATION AT ARG-140.
[9]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-85, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[10]"Structure of the nuclear factor ALY: insights into post-transcriptional regulatory and mRNA nuclear export processes."
Perez-Alvarado G.C., Martinez-Yamout M., Allen M.M., Grosschedl R., Dyson H.J., Wright P.E.
Biochemistry 42:7348-7357(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 105-182.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_035698.1. NM_011568.1.
UniGeneMm.1886.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NO8NMR-A77-182[»]
ProteinModelPortalO08583.
SMRO08583. Positions 1-187.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204102. 3 interactions.
DIPDIP-59977N.
IntActO08583. 2 interactions.
MINTMINT-1867899.

PTM databases

PhosphoSiteO08583.

Proteomic databases

PaxDbO08583.
PRIDEO08583.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026125; ENSMUSP00000026125; ENSMUSG00000025134. [O08583-1]
GeneID21681.
KEGGmmu:21681.
UCSCuc007mtl.1. mouse. [O08583-1]

Organism-specific databases

CTD10189.
MGIMGI:1341044. Alyref.

Phylogenomic databases

eggNOGNOG316507.
GeneTreeENSGT00410000025615.
HOGENOMHOG000239962.
HOVERGENHBG054806.
InParanoidQ0VBL5.
KOK12881.
OMAGNFNGNF.
OrthoDBEOG7RBZB9.
PhylomeDBO08583.
TreeFamTF313312.

Gene expression databases

BgeeO08583.
CleanExMM_THOC4.
GenevestigatorO08583.

Family and domain databases

Gene3D3.30.70.330. 1 hit.
InterProIPR025715. FoP_duplication.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamPF13865. FoP_duplication. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view]
SMARTSM00360. RRM. 1 hit.
[Graphical view]
PROSITEPS50102. RRM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO08583.
NextBio300988.
PROO08583.
SOURCESearch...

Entry information

Entry nameTHOC4_MOUSE
AccessionPrimary (citable) accession number: O08583
Secondary accession number(s): Q0VBL5, Q8CBM4, Q9JJW7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 121 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot