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O08583

- THOC4_MOUSE

UniProt

O08583 - THOC4_MOUSE

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Protein
THO complex subunit 4
Gene
Alyref, Aly, Ref1, Refbp1, THOC4
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.3 Publications
Acts as chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation.3 Publications

GO - Molecular functioni

  1. RNA binding Source: MGI
  2. nucleotide binding Source: InterPro
  3. single-stranded DNA binding Source: MGI

GO - Biological processi

  1. RNA splicing Source: UniProtKB-KW
  2. mRNA processing Source: UniProtKB-KW
  3. mRNA transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Biological processi

mRNA processing, mRNA splicing, mRNA transport, Transport

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

ReactomeiREACT_212343. Transport of the SLBP independent Mature mRNA.

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
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:1341044. Alyref.

Subcellular locationi

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.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. nuclear speck Source: UniProtKB-SubCell
  3. nucleus Source: MGI
  4. spliceosomal complex Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus, Spliceosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 255254THO complex subunit 4
PRO_0000081975Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By similarity
Modified residuei8 – 81Phosphoserine By similarity
Modified residuei50 – 501Omega-N-methylated arginine By similarity
Modified residuei85 – 851N6-acetyllysine1 Publication
Modified residuei93 – 931Phosphoserine By similarity
Modified residuei140 – 1401Citrulline
Modified residuei203 – 2031Dimethylated arginine; alternate By similarity
Modified residuei203 – 2031Omega-N-methylated arginine; alternate By similarity
Modified residuei218 – 2181Omega-N-methylarginine By similarity
Modified residuei237 – 2371Phosphoserine By similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Citrullination, Methylation, Phosphoprotein

Proteomic databases

MaxQBiO08583.
PaxDbiO08583.
PRIDEiO08583.

PTM databases

PhosphoSiteiO08583.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO08583.
CleanExiMM_THOC4.
GenevestigatoriO08583.

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 interactions.
DIPiDIP-59977N.
IntActiO08583. 2 interactions.
MINTiMINT-1867899.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi106 – 1116
Helixi118 – 12811
Beta strandi131 – 1377
Beta strandi147 – 1537
Helixi155 – 16511
Beta strandi176 – 1805

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NO8NMR-A77-182[»]
ProteinModelPortaliO08583.
SMRiO08583. Positions 1-187.

Miscellaneous databases

EvolutionaryTraceiO08583.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini105 – 18278RRM
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni16 – 3722Sufficient for RNA-binding, interaction with NXF1-NXT1 heterodimer By similarity
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi21 – 229209Ala/Arg/Gly-rich
Add
BLAST

Sequence similaritiesi

Belongs to the THOC4 family.

Phylogenomic databases

eggNOGiNOG316507.
GeneTreeiENSGT00410000025615.
HOGENOMiHOG000239962.
HOVERGENiHBG054806.
InParanoidiQ0VBL5.
KOiK12881.
OMAiGNFNGNF.
OrthoDBiEOG7RBZB9.
PhylomeDBiO08583.
TreeFamiTF313312.

Family and domain databases

Gene3Di3.30.70.330. 1 hit.
InterProiIPR025715. FoP_duplication.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF13865. FoP_duplication. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM00360. RRM. 1 hit.
[Graphical view]
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. Align

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

MADKMDMSLD DIIKLNRSQR GGRGGGRGRG RAGSQGGRGG AVQAAARVNR    50
GGGPMRNRPA IARGAAGGGR NRPAPYSRPK QLPDKWQHDL FDSGFGGGAG 100
VETGGKLLVS NLDFGVSDAD IQELFAEFGT LKKAAVHYDR SGRSLGTADV 150
HFERKADALK AMKQYNGVPL DGRPMNIQLV TSQIDTQRRP AQSINRGGMT 200
RNRGSGGFGG GGTRRGTRGG SRGRGRGTGR NSKQQLSAEE LDAQLDAYNA 250
RMDTS 255
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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei14 – 10592Missing in isoform 2.
VSP_008597Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS25744.1. [O08583-1 ]
RefSeqi NP_035698.1. NM_011568.1. [O08583-1 ]
UniGenei Mm.1886.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1NO8 NMR - A 77-182 [» ]
ProteinModelPortali O08583.
SMRi O08583. Positions 1-187.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204102. 4 interactions.
DIPi DIP-59977N.
IntActi O08583. 2 interactions.
MINTi MINT-1867899.

PTM databases

PhosphoSitei O08583.

Proteomic databases

MaxQBi O08583.
PaxDbi O08583.
PRIDEi O08583.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000026125 ; ENSMUSP00000026125 ; ENSMUSG00000025134 . [O08583-1 ]
GeneIDi 21681.
KEGGi mmu:21681.
UCSCi uc007mtl.1. mouse. [O08583-1 ]

Organism-specific databases

CTDi 10189.
MGIi MGI:1341044. Alyref.

Phylogenomic databases

eggNOGi NOG316507.
GeneTreei ENSGT00410000025615.
HOGENOMi HOG000239962.
HOVERGENi HBG054806.
InParanoidi Q0VBL5.
KOi K12881.
OMAi GNFNGNF.
OrthoDBi EOG7RBZB9.
PhylomeDBi O08583.
TreeFami TF313312.

Enzyme and pathway databases

Reactomei REACT_212343. Transport of the SLBP independent Mature mRNA.

Miscellaneous databases

EvolutionaryTracei O08583.
NextBioi 300988.
PROi O08583.
SOURCEi Search...

Gene expression databases

Bgeei O08583.
CleanExi MM_THOC4.
Genevestigatori O08583.

Family and domain databases

Gene3Di 3.30.70.330. 1 hit.
InterProi IPR025715. FoP_duplication.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view ]
Pfami PF13865. FoP_duplication. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view ]
SMARTi SM00360. RRM. 1 hit.
[Graphical view ]
PROSITEi PS50102. RRM. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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. 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.

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: September 3, 2014
This is version 125 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

External Data

Dasty 3

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